Meeting Program and Abstracts

HIGHLIGHTED ORAL 1

Autoimmunity Clinical Highlighted Oral

THE USE OF MEDICAL THERAPY FOR THYROID EYE DISEASE IN THE ERA OF TEPROTUMUMAB

Kharisa Rachmasari*, David Toro‐Tobon, Lilly Wagner, Andrea Tooley, Layla Abdul Jabbar, Marius Stan

Mayo Clinic Rochester, USA

Objective: Teprotumumab was approved for thyroid eye disease (TED) by the Food and Drug Administration (FDA) in January 2020. This study investigates clinical practice changes before and after Teprotumumab era.

Methods: A retrospective review was conducted on adult patients with TED who were treated in a multicenter health system between 2018 and 2022. Demographics, clinical characteristics, disease activity based on clinical activity score (CAS), proptosis, diplopia, disease severity based on EUGOGO classification, treatment choice and types of insurance were analyzed.

Results: A total of 74 patients with active, moderate to severe TED were identified, 33 received Teprotumumab, 19 corticosteroids, 8 Tocilizumab, and 14 patients did not receive medical therapy despite medical recommendation. Of 74 medical recommendations, around half (n = 39; 52.7%), were made collaboratively by endocrinologist and ophthalmologist in a specialized TED clinic. Prior to Teprotumumab availability, 18 patients were recommended medical therapy, of dwhich the majority received corticosteroids (n = 13) while the rest received Tocilizumab (n = 5). After Teprotumumab became available, 56 patients were recommended medical therapy: the majority (n = 33) received Teprotumumab, 6 corticosteroids, 3 Tocilizumab, while 14 patients did not receive medical therapy. All these 14 patients were advised for Teprotumumab. The most frequent factors contributing to the discordance between physicians' recommendations and therapy received were patients' refusal (n = 7) and insurance denial (n = 3). Of 7 patients who refused medical therapy, 5 patients declined due to side effects concerns. Our safety analysis of patients who ultimately received therapy indicates that Teprotumumab was associated with weight loss (27.3%), otic changes (27.3%), and hyperglycemia (18.2%), while corticosteroids were associated with insomnia (15.8%). Furthermore, one patient in the Teprotumumab group developed sepsis and one patient in the Tocilizumab group had an infusion reaction requiring urgent hospitalization.

Conclusion: In the era of Teprotumumab, more patients with active, moderate‐severe TED were evaluated for medical therapy. However, this did not translate into every evaluated patient receiving the recommended medical treatment, mainly due to safety concerns and accessibility of the medication. Efforts to address these challenges should focus on the identification of risk factors for adverse effects and health care policy adjustments.

HIGHLIGHTED ORAL 2

Iodine Uptake and Metabolism Clinical Highlighted Oral

ASSESSMENT OF IODINE STATUS IN U.S. WOMEN OF REPRODUCTIVE AGE AND PREGNANT WOMEN: NHANES 2001‐2020

Cheng Han*, Sun Lee, Carol Peng, Elizabeth Pearce

Boston University Chobanian & Avedisian School of Medicine, USA

Background: Iodine is an essential micronutrient required for the synthesis of thyroid hormones, which are critical for fetal brain development and growth. Iodine deficiency during pregnancy can lead to adverse outcomes including child cognitive impairment. We aimed to evaluate recent trends in urinary iodine concentration (UIC) levels in U.S. women of reproductive age and pregnant women, using data from the NHANES database.

Methods: Representative samples of U.S. reproductive age and pregnant women were enrolled in NHANES 2001–2020 across 5 cycles: 2001–2004, 2005–2008, 2009–2012, 2013–2016, and 2017–2020. There were 24,145 reproductive age women and 1,702 pregnant women available for analysis. Descriptive data are provided. We used linear regression models to investigate associations between UIC and potential contributing factors.

Results: The median UIC levels in reproductive age women have declined from 142 μg/L to 106 μg/L (P < 0.001). Median UIC values in pregnant women remained relatively stable over the study period, ranging from 147 μg/L to 133 μg/L (Pfor trend = 0.68). Linear regression analysis indicate that UIC is significantly positively related with dairy consumption and inversely associated with education level and socioeconomic status in reproductive age women. UIC is only positively related with dairy consumption in pregnant women.

Conclusions: The study uncovered a worrying decline in UIC levels in reproductive age women in the US over the last two decades. While the UIC remained stable in pregnant women, it still falls below the WHO's recommended criterion of 150 μg/L for iodine deficiency during pregnancy. The findings of the study emphasize the importance of taking measures to ensure sufficient iodine intake among reproductive age women and during pregnancy.

HIGHLIGHTED ORAL 3

Thyroid Cancer Basic Highlighted Oral

TET2‐MUTANT CLONAL HEMATOPOIESIS DRIVES RESISTANCE TO MAPK INHIBITORS IN BRAF^V600E ‐MUTANT ANAPLASTIC THYROID CANCER

Vera Tiedje*¹, Pablo Sánchez Vela¹, Avi Srivastava², Brian Untch³, Laura Boucai³, Stephanie Lobagouh³, Sebastiá Franch Expósito³, Tianyue Qin³, Aishwarya Krishnan¹, Anthony Martinez Benitez³, Jillian Greenberg⁴, Gnana Krishnamoorthy³, Kelly Bolton⁵, Ahmet Zehir³, Rahul Satija², Robert Bowman³, Jeffrey Knauf³, Sean Devlin³, Larry Norton³, Michael Berger³, Ross Levine³, James Fagin³

¹Memorial Sloan Kettering Cancer Center, USA,²New York Genome Center, USA,³Memorial Sloan Kettering Cancer Center, USA,⁴Memorial Sloan Kettering Cancer Center, USA,⁵Washington University School of Medicine, USA

Background/Objective: BRAF^V600E ‐mutant anaplastic thyroid cancers (ATCs) are heavily infiltrated with myeloid cells. Combined BRAF/MEK inhibition has shown remarkable responses in BRAF^V600E ‐mutant ATCs. Clonal Hematopoiesis (CH) is caused by increased fitness of hematopoietic stem‐progenitors conferred by somatic mutations in genes such as the epigenetic modifier TET2, leading to overrepresentation of mutant clones in blood, especially among myeloid cells. The incidence of CH increases with age and radiation exposure and is a risk factor for hematologic malignancies, atherosclerosis and other comorbid conditions of aging. Thyroid cancers are the most common tumor associated with CH. CH is associated with worse outcomes in other solid tumor patients, although the specific consequences of CH on therapy response are unknown.

Methods: We annotated the MSK‐IMPACT cohort and generated mouse models with concurrent CH and ATC. We performed competitive bone marrow transplants (bmt) from tamoxifen‐treated C57BL/6J CD45.2⁺ mice harboring a HSPC‐specific recombinase (SclCreERT) and a TdTomato reporter to specifically delete and identify excised Tet2 cells into irradiated CD45.1⁺ mice. After engraftment mice were injected orthotopically with Braf^V600E/Tp53^‐/‐ (TBP3743) ATC cells. Mice were treated with dab/tram vs vehicle. Multispectral flow cytometry and CITE‐scRNASeq analysis was performed.

Results: CH was associated with decreased overall survival in thyroid cancer patients, including ATC. In our murine models Tet2^‐/‐ CD45⁺ cells were enriched in the TME relative to peripheral blood ‐ primarily monocytes, macrophages and dendritic cells. Tumor growth in vehicle conditions did not differ. Dab/tram significantly inhibited tumor size assessed by ultrasound after 1‐ and 2‐week treatment compared to baseline in Wt, but not in Tet2^‐/‐ bmt mice, indicative of MAPKi resistance in ATCs infiltrated with Tet2‐mutant clones. Dab/tram failed to fully inhibit MAPK transcriptional output in Tet2^‐/‐ vs WT bmt mice. Instead, aberrant Jak‐Stat, VEGF, and hypoxia signatures were seen in tumor and Tet2^‐/‐ myeloid cells. Tet2^‐/‐ myeloid cells in dab/tram‐treated ATCs had increased expression of the chemokines Ccl2, Ccl6, Ccl7, Ccl9 and 12, which are lead candidate drivers of resistance to MAPK pathway blockade.

Conclusions: CH‐mutations lead to resistance to dab/tram in murine ATC. Our work opens new avenues for the selective targeting of tumor‐promoting inflammation in ATC.

HIGHLIGHTED ORAL 4

Thyroid Nodules and Goiter Translational Highlighted Oral

RISK OF THYROID NODULES IN RESIDENTS OF UKRAINE EXPOSED AS CHILDREN OR ADOLESCENTS TO IODINE‐131 FROM THE CHORNOBYL ACCIDENT

Elizabeth Cahoon*¹, Eric Grimm², Kiyohiko Mabuchi¹, Zhi‐Ming Mai¹, Rui Zhang¹, Vladimir Drozdovitch¹, Maureen Hatch¹, Mark Little¹, Kamau Peters¹, Tetiana Bogdanova³, Evgeniy Shelkovoy³, Viktor Shpak³, Galyna Terekhova³, Galyna Zamotayeva³, Ihor Pasteur³, Sergii Masiuk⁴, Mykola Chepurny⁴, Lydia Zablotska⁵, Robert McConnell⁶, Patrick O'Kane⁷, Mykola Tronko³, Alina Brenner¹

¹National Cancer Institute, USA,²University of Colorado School of Medicine, USA,³V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine, Ukraine,⁴National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Ukraine,⁵Department of Epidemiology & Biostatistics School of Medicine, University of California, San Francisco, USA,⁶Columbia University, USA,⁷Thomas Jefferson University Hospital, USA

External exposure to ionizing radiation during childhood is one of the most established risk factors for thyroid cancer. However, the relationship between radioactive iodine 131 (I‐131) exposure and the development of thyroid nodules is not well‐characterized and risk estimates vary widely.

The objective of this study is to evaluate the association between childhood I‐131 exposure and prevalence of ultrasound detected thyroid nodules overall and by the following case groups: nodule histology/cytology (neoplastic / suspicious / non‐neoplastic), size (<10 mm / ≥10 mm), and number (single / multiple).

We assessed prevalence of thyroid nodules at first thyroid screening examination conducted in 1998‐2000 (median population age 21.5 years at screening) in residents of Ukraine aged <18 years at the time of the Chernobyl accident (April 26, 1986) with direct thyroid radioactivity measurements. Thyroid doses in Gray (Gy) ranged from 0.0003 Gy to 31 Gy with a mean of 0.53 Gy. Excess odds ratios (EOR) per Gy and 95% confidence intervals (95% CI) were estimated using logistic regression.

Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. We found significant dose‐response based on a linear EOR model for each case group. However, consistent with downturn or flattening in category‐specific EORs at high doses, there was evidence of exponential departure from linearity for all thyroid nodules (p‐value = 0.02). Below 5 Gy, the dose‐responses were consistent with linearity for each case group and for all nodules, the EOR/Gy was 1.11 (95% CI: 0.65, 1.77). Among subjects with doses <5 Gy, the EOR/Gy for neoplastic nodules (5.35; 95% CI: 2.19, 15.5) was significantly higher than for non‐neoplastic nodules (EOR/Gy = 0.24; 95% CI: ‐0.07, 0.74), but did not vary by nodule size or number.

Increased I‐131 risk for all prevalent thyroid nodules and by nodule histology/cytology in Ukraine is consistent with findings from a parallel study in Belarus. Analyses of incident thyroid nodules may help explain differences in dose‐response patterns by nodule size between Ukraine and Belarus and provide insights into thyroid nodule etiology.

ORAL 5

Thyroid Cancer Clinical Oral

CHECKPOINT INHIBITION IN ADDITION TO DABRAFENIB + TRAMETINIB (DT) FOR BRAFV600E MUTATED ANAPLASTIC THYROID CARCINOMA (BRAFm‐ATC)

Sarah Hamidi*, Priyanka Iyer, Maria Gule‐Monroe, Anastasios Maniakas, Ramona Dadu, Mark Zafereo, Jennifer Wang, Naifa Busaidy, Maria Cabanillas

MD Anderson Cancer Center, USA

Background: DT has revolutionized treatment of BRAFm‐ATC. However, patients eventually develop resistance. Single‐agent anti‐PD1 inhibitors, like pembrolizumab, have shown responses of 19% in ATC. BRAF‐targeted therapy prior to surgery (neoadjuvant) has also shown improvement in survival. We studied the efficacy and safety of combination of DT plus pembrolizumab (DTP) as initial treatment or in neoadjuvant setting, compared to current standard of care DT alone.

Methods: Retrospective study of patients with BRAFm‐ATC treated with first‐line DT or DTP between 1/2014‐3/2023 (outside of trial or on reported clinical trial). Three cohorts were evaluated: DT, DTP (pembrolizumab added before or after progression), and neoadjuvant (pembrolizumab added before or after surgery). Primary endpoint was median overall survival (mOS) between DT and DTP; secondary endpoints: median progression‐free survival (mPFS) and response rate on DT vs DTP, mOS in neoadjuvant vs other arms. Best response was assessed using RECISTv1.1; survival by Kaplan‐Meier method.

Results: 94/158 BRAFm‐ATCs were included: n = 23 in DT, n = 48 in DTP and n = 23 in neoadjuvant. Baseline demographics were similar between groups, including presence of metastatic disease at start of treatment (87.0% in DT, 79.2% in DTP, 65.2% in neoadjuvant; p = 0.196). 44/45 (98%) evaluable specimens had a PDL1 score >1% in pembrolizumab‐treated patients. Median follow‐up: 102.0months (range:0.6‐102) DT; 28.0months (range:3‐63) DTP; 42.0months (range:7‐75) neoadjuvant. mOS was significantly different between DT and all other groups: 7.0months (95%CI,2.5–11.4) DT; 17.0months (95%CI,11.9–22.1) DTP; 63.0months (95%CI,15.6–110.3) neoadjuvant; (p < 0.001). 12‐/24‐month survival rates: 33.7%/28.9% DT; 60.2%/36.5% DTP; 81.6%/75.4% neoadjuvant. mPFS was also significantly longer with DTP (11.0months [95%CI,7.0–15.0]) compared to DT alone (4.0months [95%CI,0.7–7.3]) as initial treatment (p = 0.049). Response rate, defined as complete+partial responses, was 64.5% with DT and 73.3% with DTP. No grade 5 adverse events (AEs) occurred, but 32.4% had immune‐related AEs, most frequently colitis and hepatitis.

Conclusions: Our results suggest that in BRAFm‐ATC, a multimodal approach including addition of pembrolizumab to DT, and surgical resection of the primary tumor after initial BRAF‐targeted therapy (in selected patients), may provide a significant survival benefit. However, conclusions are limited by the retrospective nature of the study and smaller number of patients in DT group. Additional prospective data are needed to confirm this observation.

ORAL 6

Thyroid Cancer Translational Oral

THE IDENTIFICATION OF NOVEL GENETIC VULNERABILITIES IN ANAPLASTIC THYROID CANCER CELLS TO OVERCOME RESISTANCE TO BRAF^V600E INHIBITOR USING A GENOME‐WIDE CRISPR SCREEN

Haojian Li¹, Xiaolin Wu², David Sun², Urbain Weyemi¹, Myriem Boufraqech*¹

¹NCI, USA,²Frederick National Laboratory for Cancer Research, USA

Objective: Anaplastic thyroid cancer (ATC) cells are particularly resistant to most common therapeutic strategies. There are major gaps in our understanding of the mechanism of resistance in ATC cancer cells carrying BRAFV600E mutation. Most of the current targeted therapies using BRAFV600E inhibitors have failed, and the combination approach in which mutant BRAF inhibitors were coupled with other targeted therapies including TKI have shown limited efficacy in patients with advanced thyroid cancer. Therefore, there is an urgent need to identify new determinants of resistance to BRAFV600E inhibitors and filling these gaps will fundamentally reshape our approach to ATC treatment. Recent studies demonstrated that BRAF^V600E ‐driven advanced and metastatic thyroid cancer are not sensitive to monotherapies with mutant BRAF inhibitors due to acquired resistance mediated by genetic alterations and/or activation of metabolic and oncogenic signaling pathways. Our overall hypothesis is that BRAF^V600E ‐driven ATC cancer cells heavily rely on certain genes to survive most treatments targeting mutant BRAF, and CRISPR/Cas9‐based sgRNAs directed against these specific genes would enhance cell death by mutant BRAF inhibitors.

Methods: To identify genetic vulnerabilities that sensitize ATC cancer cells to mutant BRAF inhibitors, we conducted a CRISPR‐based screen of genes linked to resistance to BRAF inhibitors and cancer cell survival. First, using BRAFV600E ‐driven ATC cell line 8505c, we harnessed a human CRISPR knockout library of 19,050 genes to identify genes whose loss enhances cell death by the BRAFV600E selective inhibitor Dabrafenib. Dabrafenib has a better toxicity profile compared to vemurafenib, and was recently approved by the FDA for the treatment of advanced and metastatic thyroid cancer. The human GeCKO v2 CRISPR library A that has 65,386 unique sgRNAs, targeting 19,052 protein‐coding genes, and 1864 microRNAs was used to generate mutant cells pool. These cells were then treated with Dabrafenib for 7 days, followed by genomic DNA extraction, PCR amplification, and Next Generation Sequencing.

Results: Utilizing MAGeCKFlute pipeline analysis combined with transcriptomics profiling of cells exposed for 7 days to BRAF^V600E inhibitor, we unveiled several essential genes required for survival upon dabrafenib treatment, among which mitochondrial stress genes are uniquely prominent. Our preliminary findings strongly suggest a key role for metabolic reprogramming in resistance to BRAF^V600E inhibitors.

Conclusion: We identified genetic determinants of resistance to mutant BRAF inhibitors. Our study unveils a unique understanding of how ATC cells survive upon BRAF^V600E inhibitors treatment.

ORAL 7

Thyroid Cancer Clinical Oral

EFFICACY AND PREDICTORS OF RESPONSE TO RADIOACTIVE IODINE REDIFFERENTIATION THERAPY IN PREVIOUSLY IODINE REFRACTORY PAPILLARY THYROID CARCINOMAS

David Toro‐Tobon*, John Morris, Crystal Hilger, Candy Peskey, Jolanta Durski, Mabel Ryder

Mayo Clinic, USA

Objective: Redifferentiation therapy (RDT) variably restores radioactive iodine (RAI) avidity in patients with RAI refractory (RAIR) differentiated thyroid cancers (DTC). This study examined predictors of RAI avidity and overall outcomes in a subgroup of patients with papillary thyroid cancer (PTC) undergoing RDT.

Methods: This is a retrospective review of 23 patients with RECIST‐progressive metastatic RAIR‐PTC who underwent RDT between 2017 and 2022 at Mayo Clinic. All received MEK inhibitor or combination BRAF‐MEK inhibitors for 4 weeks. Those with increased RAI avidity at week 3 (responders) received high‐dose I‐131 therapy.

Results: 4 of 11 (36.3%) with classical PTC (C‐PTC), 2 of 4 (50%) with tall cell variant‐PTCs (TCV‐PTC), 4 of 4 (100%) with follicular variant‐PTCs (FV‐PTC), and 2 of 4 (50%) tall cell features‐PTCs (TCF‐PTC) had restored RAI avidity following RDT using dabrafenib/trametinib (7 BRAF mutant) or trametinib (4 RAS mutant). All 5 (100%) RAS mutant tumors (2 C‐PTC and 3 FV‐PTC) had restored RAI avidity compared to 7 (38.8%) of BRAF mutant tumors (2 C‐PTC, 2 TCV‐PTC, 2 TCF‐PTC, and 1 FV‐PTC). The median thyroglobulin was 211 mIU/L in responders and 46 mIU/L in nonresponders (p = 0.06). Patients with FV‐PTC (p = 0.03), RAS mutation (p = 0.01), distant metastasis (p = 0.05), no locoregional disease at initial staging (p < 0.01), bone metastasis (p = 0.03), prior radiotherapy (p = 0.01), or prior systemic therapy (p = 0.01) were more likely to have restored RAI avidity. The 12 responders received a median dose of 243.9 mCi. Regardless of I‐131 therapy, responders and non‐responders had similar RECIST objective responses (complete or partial response, stable disease, non‐complete response/non‐progressive disease) (81.8% and 80%, p = 0.9), median progression‐free survival (18 and 9 months, p = 0.45), overall survival (27 months and no mortality, p = 0.07), and time to any additional therapy (18 and 12 months, p = 0.9). Of the responders, 1 patient experienced histologic transformation to anaplastic thyroid cancer and 4 (17.3%) died.

Conclusion: RDT restores RAI avidity in select patients with PTC, especially those with follicular and RAS phenotypes. RECIST responses were seen in both responders and non‐responders, with or without RAI therapy. Larger randomized studies are needed to confirm predictors of response and to objectively examine outcomes and safety.

ORAL 8

Thyroid Cancer Translational Oral

RATIONAL DRUG DESIGN OF VCP INHIBITORS TO ENHANCE NIS FUNCTION IN RADIOIODIDE THERAPY

Martin Read*¹, Ling Zha¹, Katie Brookes¹, Jana Kim², Benjamin Small^3,4, Merve Kocbiyik¹, Selvambigai Manivannan¹, Giovanni Bottegoni^5,6, Liam Cox⁷, Vinodh Kannappan^3,4, Weiguang Wang^3,4, Kavitha Sunassee², Philip Blower², Hannah Nieto¹, Vicki Smith¹, Christopher McCabe¹

¹Institute of Metabolism and Systems Research, University of Birmingham, United Kingdom,²School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom,³Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, United Kingdom,⁴Disulfican Ltd, University of Wolverhampton Science Park, United Kingdom,⁵Institute of Clinical Sciences, University of Birmingham, United Kingdom,⁶Università degli Studi di Urbino Carlo Bo, Italy,⁷School of Chemistry, University of Birmingham, United Kingdom

Objective: New approaches are required to improve the efficacy of drugs that have the potential to enhance ablative radioiodide (RAI) uptake, especially in RAI‐refractory disease. Our recent experiments in multiple cellular models revealed that valosin‐containing protein inhibitors (VCPi), such as clotrimazole and disulfiram, markedly increase sodium iodide symporter (NIS) activity to promote RAI uptake, but poor bioavailability diminished thyroidal impact in vivo. New drug design strategies may therefore be needed to overcome the poor water solubility and rapid metabolism of VCPi in the circulation. Here, our aim was to determine whether rational drug design and reformulation strategies improve the efficacy of VCPi on NIS function in vitro and in vivo.

Methods: Computational iterative drug design was accompanied by de novo drug synthesis. RAI (¹²⁵I) uptake assays were used to monitor NIS function in vitro. Technetium‐99m pertechnetate (^99mTc) uptake after intravenous administration was used to evaluate NIS function in wild‐type BALB/c mice.

Results: Based on 3D modelling and iterative drug construction, we designed 21 novel analogues based on clotrimazole and the allosteric VCPi UPDC30425, all with improved predicted bioavailability (LogP), and synthesised 4 de novo compounds based on CryoEM high‐resolution features of VCPi NMS873 docking to VCP. In parallel, we prepared albumin nano‐encapsulated copper‐diethyldithiocarbamate [Cu(DDC)₂‐alb] ‐ a stabilised reformulation of a disulfiram metabolite. Subsequent testing revealed that while several clotrimazole analogues specifically increased RAI uptake, the greatest impact was observed with Cu(DDC)₂‐alb treatment in thyroidal TPC‐1‐NIS (2.8‐fold; P < 0.01) and 8505C‐NIS cells (3.0‐fold; P < 0.01). Importantly, the intraperitoneal administration of Cu(DDC)₂‐alb significantly induced thyroidal ^99mTc‐uptake after 30 min (∼40%; n = 11; 3 mg/kg dose; P < 0.001) in BALB/c mice, as well as increasing thyroidal NIS (1.9‐fold; P < 0.01), thyroid peroxidase (1.8‐fold; P < 0.001) and thyroglobulin mRNA (1.3‐fold; P < 0.05) expression. A significant positive correlation was apparent between thyroidal ^99mTc‐uptake and NIS mRNA (r_s = 0.4477; P = 0.0169) in Cu(DDC)₂‐alb treated mice, uniting drug effects on NIS expression and function.

Conclusion: Our study demonstrates a promising drug strategy utilising a disulfiram metabolite to enhance NIS function in vivo, with clinical potential to improve treatment in RAI‐refractory thyroid cancer.

ORAL 9

Thyroid Hormone Action Metabolism and Regulation Basic Oral

LIVER DEVELOPMENT DURING XENOPUS TROPICALIS METAMORPHOSIS IS CONTROLLED BY T3‐ACTIVATION OF WNT SIGNALING

Yuta Tanizaki*, Shouhong Wang, Hongen Zhang, Yuki Shibata, Yun‐Bo Shi

National Institutes of Health, USA

Thyroid hormone (T3) regulates the vertebrate development, growth, and metabolism through T3 receptors (TRs), TRα and TRβ. The serum T3 concentration is increased during postembryonic development, when organs/tissues, such as liver, are remodeled from larval/embryonic form to adult form. Due to maternal influence in mammals, the underlying mechanisms of organs/tissue development during post‐embryonic development remain unclear. Since the process of remodeling during Xenopus tropicalis metamorphosis resembles human organs/tissues development during post embryonic development, we have been investigated molecular mechanisms of tissue remodeling by using Xenopus tropicalis as a model of human development. Here, we studied whether liver development during metamorphosis is regulated by T3, and underlying mechanismas of T3 on liver development. It is known that liver metamorphosis involves increased cell proliferation, hepatocyte hypertrophy, and activation of urea cycle gene expression, a key feature of adult/mature liver in vertebrates. We generated X. tropicalis animals with both TRα and TRβ genes knocked out and found that the TR double knockout (TRdKO) liver had developmental defects such as reduced cell proliferation and failure to undergo hepatocyte hypertrophy or activate the expression of urea cycle genes. These indicate that lliver developmet is under the control of T3. To reveal the molecular pathways regulated by T3 during liver remodeling, we performed RNA‐seq analysis and found that T3 activated canonical Wnt pathway in the liver and this pathway is also activated during metamorphosis. Particularly, Wnt11 was activated in both fibroblasts and hepatic cells, and in turn, likely acted to promote proliferation and maturation of hepatocytes. Our findings resemble those from studies on liver regeneration in mammals. Thus, our study has the potential to bring new insights on not only how T3 regulates liver development but also potential means to improve liver regeneration. The further analysis of Xenopus liver metamorphosis should help to understand human hepatic development and the physiological defects in hepatic failure patients and provide potential new avenues for intervention.

ORAL 10

Thyroid Hormone Action Metabolism and Regulation Basic Oral

A NEW TRANSGENIC MOUSE LINE TO ALLOW TESTING THE RELATIONSHIPS BETWEEN THYROID HORMONE, MITOCHONDRIAL MORPHOLOGY, AND GAP JUNCTION CONNECTIVITY WITH SUBCELLULAR PRECISION

Randy Stout*, Lars Udo‐Bellner

New York Institute of Technology, USA

We have developed a new tool for studying the availability of triiodothyronine (T3) with high sensitivity and temporal resolution at the single cell level. Our approach is based on modification and further development of a fluorescent protein‐based sensor previously developed by others (the Hager laboratory, NIH). We added a fluorescent protein marker for the cell nucleus to facilitate easier use of the thyroid sensor in live cells and tissues. To extend the utility of our optical thyroid sensor, we combined it with an optical reporter for mitochondrial morphology and function, creating a three‐part thyroid sensor transgene construct we called ThSnR‐BluN‐GnMt.

We confirmed that ThSnR‐BluN‐GnMt works in multiple cell types with high sensitivity, detecting changes in the sensor with less than 20nM T3 within an hour of T3 application. As with other cellular parameters in stable cell lines, we also observed cell to cell variability in stable cell lines using the single‐cell thyroid hormone sensor.

In April of 2023, we received confirmation that a transgenic mouse line had been developed with the ThSnR‐BluN‐GnMt expected to be expressed in all cells of the mouse body. We have several initial studies planned, with the first being to characterize the transgene expression in various tissues and responsiveness to thyroidectomy. Additionally, we plan to examine the effects of diminished thyroid hormone production on individual nuclei of the hypothalamus, where we expect to observe changes to mitochondrial morphology in specific subpopulations of hypothalamic tanycytes and decreased thyroid signaling in the astrocytes and neurons of the median eminence, arcuate nucleus, and paraventricular nucleus. To achieve this, we will combine the new ThSnR‐BluN‐GnMt mice with advanced microscopy and immunostaining techniques to mark cell type and quantify the relationship between thyroid hormone, cell type, and subcellular morphology.

We believe the ThSnR‐BluN‐GnMt transgene and mouse line will be a valuable tool in efforts to understand how thyroid hormone deficiency can lead to changes in brain function, heart disease, and other conditions. We will report our findings from the ThSnR‐BluN‐GnMt mice and discuss ways they can be used by the wider thyroid research community.

ORAL 11

Disorders of Thyroid Function Clinical Oral

IN VITRO PHARMACOLOGY AND PHASE 1/2 RESULTS OF VRDN‐001, A FULL ANTAGONIST ANTIBODY TO IGF‐1 RECEPTOR IN THYROID EYE DISEASE (TED)

Kimberly Cockerham*¹, Shaoib Ugradar², Raymond Douglas³, Roger Turbin⁴, Rosa Tang⁵, Navdeep Nijhawan⁶, Andrea Kossler⁷, Chantal Boisvert⁸, Wendy Lee⁹, Michael Yen¹⁰, David Kaufman¹¹, Michael Yoon¹², Vahe Bedian¹³, Barrett Katz¹³

¹Stanford University Department of Ophthalmology at Byers Eye Institute, USA,²The UCLA Stein Eye Institute, USA,³Cedars Sinai Medical Center, USA,⁴Rutgers New Jersey Medical School, USA,⁵Eye Wellness Center– Neuro‐Eye Clinical Trials, Inc., USA,⁶Oshawa Clinic, Canada,⁷Stanford Department of Ophthalmology at Byers Eye Institute, USA,⁸Duke Eye Center, USA,⁹Bascom Palmer Eye Institute, USA,¹⁰Baylor College of Medicine, Alkek Eye Center, USA,¹¹Michigan State University Department of Neurology & Ophthalmology, USA,¹²Harvard Medical School, Massachusetts Eye and Ear Infirmary, USA,¹³Viridian Therapeutics, USA

Introduction: Antagonism of the IGF‐1 receptor (IGF‐1R) has been shown to reduce TED‐related inflammation and proptosis. VRDN‐001, a high‐affinity antagonist antibody to IGF‐1R, has distinct pharmacological properties that may enable differentiated dosing and better efficacy than observed with other antibodies. We assessed VRDN‐001 in vitro pharmacology compared with teprotumumab and clinical proof of concept in a phase 1/2 randomized controlled trial (NCT05176639).

Methods: Inhibition of biotinylated IGF‐1 binding to IGF‐1R expressing FreeStyle™ 293‐F cells was assessed by flow cytometry; inhibition of IGF‐1 mediated signaling (phosphorylation of IGF‐1R and AKT) was assessed in primary human ocular choroidal fibroblasts. In the phase 1/2 trial, adults with active moderate‐to‐severe TED and clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 3, 10, or 20 mg/kg VRDN‐001 or placebo. Safety and efficacy through 6 weeks were assessed.

Results: In the in vitro studies, VRDN‐001 provided near‐complete inhibition of IGF‐1 binding and IGF‐1 mediated signaling at concentrations ≥50 nM; in contrast, teprotumumab provided only partial inhibition of IGF‐1 binding and IGF‐1R signaling. In the clinical trial of VRDN‐001 [(n = 21) vs placebo (n = 6)], all 3 doses of VRDN‐001 showed similar reduction in proptosis and clinical activity at 6 weeks. Across all doses, the overall responder rate (% of patients with ≥2‐mm reduction in proptosis and ≥2‐point reduction in CAS) was 67% (14/21; VRDN‐001) vs 20% (1/5; placebo). Proptosis response (≥2‐mm reduction) was achieved by 15 VRDN‐001 and 2 placebo patients. Mean reduction in CAS score was 4.1 (VRDN‐001) vs 1.8 (placebo), and CAS decreased to 0 or 1 for 62% (13/21; VRDN‐001) vs 20% (1/5; placebo). Complete resolution of diplopia occurred for 54% (7/13; VRDN‐001) vs 0% (0/3; placebo). AEs were mostly mild, with no severe or serious AEs reported.

Discussion/Conclusions: VRDN‐001 provides near‐complete inhibition of IGF‐1 binding and IGF‐1R signaling, which may explain the rapid, marked reductions in proptosis and clinical activity score observed in patients with TED enrolled in this trial. The potential clinical efficacy and safety of VRDN‐001 in TED are being further assessed in the THRIVE phase 3 randomized controlled trial.

ORAL 12

Disorders of Thyroid Function Clinical Oral

MAJOR CARDIOVASCULAR OUTCOMES OF HYPERTHYROIDISM TREATED WITH ANTITHYROID DRUG, RADIOACTIVE IODINE, OR THYROIDECTOMY: A TAIWANESE NATIONAL COHORT

Carol Chiung‐Hui Peng*^1,2, Yu‐Jie Lin³, Sun Lee¹, Ching‐Hui Loh², Huei‐Kai Huang⁴, Elizabeth Pearce¹

¹Section of Endocrinology, Diabetes, Nutrition & Weight Management, Boston University Chobanian & Avedisian School of Medicine, USA,²Center for Aging and Health, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan,³Health Information Center, Tzu Chi University, Taiwan,⁴Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan

Objectives: Excessive thyroid hormone levels increase the risks for adverse cardiovascular outcomes. Studies are lacking in comparing long‐term outcomes associated with the three available treatments for hyperthyroidism, anti‐thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy. We aimed to compare the risks of major adverse cardiovascular events (MACE) and all‐cause mortality among hyperthyroid patients treated with ATD, RAI, or surgery.

Methods: This was a nationwide retrospective cohort study using data from Taiwan's National Health Insurance Research Database. Patients aged ≥20 years who were newly diagnosed with hyperthyroidism between 2011 and 2020 were enrolled. Groups were defined based on initial treatment received within 18 months after diagnosis. Patients in the ATD group received only ATD treatment. Patients in the RAI and surgery groups could receive ATD before definitive therapy. Subjects were followed until the development of MACE, death, or the end of 2020. The primary outcomes were MACE (composite of acute myocardial infarction, stroke, heart failure, and cardiovascular mortality) and all‐cause mortality. Propensity score‐based weighting was used to reduce between‐group differences in baseline characteristics. Cox proportional hazards models were used to estimate hazard ratios. Kaplan‐Meier curves were used to assess the cumulative incidence of outcomes.

Results: 114,315 patients (mean age 44.1 ± 13.6 years, 73.2 % female) were followed for a mean (SD) of 4.4 (2.3) years. 93.5% were treated with ATD alone, 1.1% received RAI, and 5.1% underwent surgery. Among the cohort, 1742 patients in the ATD group, 12 in the RAI group, and 88 in the surgery group developed MACE. Patients undergoing surgery had a significantly lower risk of MACE (HR = 0.76, 95% CI 0.59 – 0.98, p = 0.035) and all‐cause mortality (HR = 0.53, 95% CI 0.41 – 0.68, p < 0.001) relative to ATD users. Treatment with RAI compared to ATD was associated with a significantly lower risk of MACE (HR = 0.45, 95% CI 0.22 – 0.93, p = 0.030). Sensitivity analysis excluding incidental thyroid cancer found that post‐hyperthyroidism diagnosis did not alter results.

Conclusions: Compared to ATD, thyroidectomy in patients with newly diagnosed hyperthyroidism was associated with lower risks of MACE and all‐cause mortality, while RAI was associated with a lower risk of MACE.

ORAL 13

Disorders of Thyroid Function Clinical Oral

INCIDENCE OF THYROID EYE DISEASE IN THE UNITED STATES: ANALYSIS OF A HEALTHCARE CLAIMS DATABASE

Marius Stan¹, Lilly Wagner¹, Kharisa Rachmasari¹, Brett Venker², Joel Arackal³, Jingyu Wang², Jennifer Schwinn⁴, Paola Mina‐Osorio*⁴

¹Mayo Clinic, USA,²Roivant Sciences, Ltd., USA,³University of Health Sciences and Pharmacy, USA,⁴Immunovant, Inc., USA

Introduction: Thyroid eye disease (TED) is a debilitating, potentially sight‐threatening orbital disorder caused by pathogenic anti‐TSHR antibodies targeting orbital fibroblasts. It is the most common extrathyroidal manifestation of Graves' disease and may lead to a broad range of ophthalmic manifestations. Current estimates of its incidence in the United States (US) are lacking.

Objective: To estimate the incidence of TED in the US and describe patient demographics.

Methods: This retrospective study used Inovalon data from 2016 through 2020, which covers nearly 170 million individuals and contains professional and institutional medical claims from Commercial, Medicare Advantage, and Medicaid payers. Specific criteria to identify these patients were established by three TED specialists. Patients required: 1) a diagnosis of hyperthyroidism consistent with Graves' disease or radioactive iodine‐induced hypothyroidism and 2) a diagnosis or procedure code indicative of TED. Two different incidence estimates were calculated. The first reflects a narrower definition (specific) including a limited number of diagnoses and procedures indicative of TED, while the second accounts for a broader definition of TED (sensitive). We conducted incidence estimations across 2018 and 2019 and assessed patient demographics and provider characteristics for these populations.

Results: For specific incidence we found a raw rate of 4.15 patients per 100,000 patients‐years, with an age and gender adjusted rate of 2.05 per 100,000 in men and 6.59 in women. The sensitive incidence calculation produced an overall raw rate of 8.07 per 100,000 patient‐years. When adjusted for age and gender this produced a rate of 4.27 per 100,000 in men and 13.49 per 100,000 in women.

Discussion: Lack of a specific ICD code for TED makes precise identification of TED patients using claims data challenging. A narrow algorithm aiming for specificity yields smaller incidence numbers than previously reported (Bartley, 1995). The more sensitive definition yields incidence numbers in line with previous reports. Exclusion of TED cases associated with autoimmune hypothyroidism and euthyroidism are likely contributing to an underestimation of TED. Overall, TED incidence has not increased significantly over the years and creating a specific ICD code for TED is crucial to help advance health care planning and management of this disease.

POSTER 200

Autoimmunity Basic Poster

THE POTENTIAL ROLE OF PREVENTING GRAVES' DISEASE BY INDUCTION OF NEONATAL TOLERANCE IN TREE SHREW

Liping Wu*, Xiaoyan Guan, Fengyi Zhao, Yue Wang, Wei Qiang, Meng Zhang, Pu Chen, Rongrong Cui, Bingyin Shi

the First Affiliated Hospital of Xi'an Jiaotong University, China

Neonatal tolerance induction is one of effective measures for preventing autoimmune diseases. The aims of this study were to obtain preventative effects in adult tree shrews by inducing antigen‐specific immune tolerance to GD in neonate. Newborn female tree shrews were administered in different ways(im, ip, sc, po) with the thyrotropin receptor (TSHR) A subunit protein. Blood was collected at 3, 13 months. GD induction was followed at 6 months with injection of recombinant adenovirus expressing TSHR A subunit. After the last injection of disease induction in adults, Tree shrews receiving neonatal antigen‐treatment with po manner failed to develop antibody response to TSHR. only 2 of 8 tree shrews immunized by ip or im administration in neonate were elicited weak anti‐TSHR antibody. There was no significant difference in the antibody positive rates between not treated and treated groups with sc injection. TT4 levels were slightly elevated in two of 8 tree shrews treated by im or ip injection and in normal range in all 8 tree shrews treated by po route. The numbers of hyperthyroidism are not statistically significant between not treated and treated groups with sc injection. Although the difference of positive rates of GD was not significant, the po treatment were seemingly more effective than the im or ip route in inducing tolerance. Compared with controls, the po, im, ip tolerance induction could reduce T cells immune response to TSHR A subunit. The number of plasmacytoid dendritic cell (pDC) was significantly higher in tree shrews treated with po, im, ip routes than that in controls (P < 0.05). The po, im, ip treatment not only significantly promoted the secretion of IL‐4, IL‐10, TGF‐β (P < 0.05), but also inhibited the production of INF‐γcompared to controls (P < 0.05). These data demonstrate that neonatal tolerance to GD can be induced by TSHR A subunit protein of po, im or ip treatment in neonatal tree shrews, and vaccine may have a potential role of preventing GD. The DC and T cell cytokines are involved in the regulation of immune tolerance.

POSTER 201

Autoimmunity Basic Poster

THYROCYTE‐SPECIFIC BMAL1 DELETION EXACERBATES EXPERIMENTAL AUTOIMMUNE THYROIDITIS BY PROMOTING LOCAL IMMUNE RESPONSES

Jinrong Fu¹, Qiting Ye², Yushu Li¹, Haixia Guan*²

¹The First Affiliated Hospital of China Medical University, China,²Guangdong Provincial People's Hospital, China

Objective: Dysregulation of the core clock gene Bmal1 expression has been implicated in a variety of inflammatory diseases. However, there is insufficient evidence suggesting its involvement in thyroid autoimmunity. The current study aimed to examine the effects of thyrocyte Bmal1 deletion on the development of autoimmune thyroiditis (AIT).

Methods: A conditional thyrocyte‐specific Bmal1 knock out mouse model (cKO) was established. To induce experimental autoimmune thyroiditis (EAT), cKO and Control (Ctrl) mice aged 8 weeks were immunized with thyroglobulin (Tg) and adjuvants at two different Zeitgeber time points (ZT6 and ZT18). The severity of EAT was evaluated by histological analysis, serum levels of thyroglobulin autoantibodies (TgAb) and inflammatory cytokines. Key immune disorders in EAT, including activation of CD4⁺T cells and intrathyroidal expression of inflammatory markers, were evaluated for mechanistic research.

Results: Thyrocyte‐specific Bmal1 deletion disrupted the oscillations of intrathyroidal clock gene expression. Both cKO and Ctrl mice showed more severe EAT when immunized at ZT6 compared with mice immunized at ZT18. Notably, cKO‐EAT mice exhibited aggravated thyroid lymphocytic infiltration, elevated TgAb and inflammatory cytokine levels compared with Ctrl‐EAT mice. Transcriptomic analysis of CD4⁺T cells showed 1114 differentially expressed genes in cKO‐EAT mice relative to Ctrl‐EAT mice, which were mainly enriched in immune system process and inflammatory responses. cKO‐EAT mice showed increased Th1, Th17 subsets, and decreased Treg subsets. Intrathyroidal accumulation of CD4⁺T cells and increased expression of Tnf‐α, Cxcr3 and Cxcl10 indicate enhanced local inflammatory responses in cKO‐EAT mice.

Conclusion: The present study demonstrated that thyrocyte‐specific Bmal1 deletion disrupted the thyroid clock and increased the severity of EAT. This was mediated by imbalanced differentiation of CD4⁺T cells and substantial increased CD4⁺T infiltration in thyroid tissue. The progression of thyroid inflammation in this model provides a previously unidentified role of Bmal1 and thyroid clock, which may serve as novel chronotherapeutic targets for the treatment of AIT.

POSTER 202

Autoimmunity Basic Poster

PROANGIOGENIC EFFECT OF THYROTROPIN RECEPTOR STIMULATING ANTIBODY IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS: A MECHANISTIC STUDY OF GOITER FORMATION IN GRAVES' DISEASE

Yue Yuan, Xingjia Li, Shuhang Xu*, Chao Liu

Nanjing University of Chinese Medicine, China

Objective: A high titer of the thyrotrophin receptor autoantibody (TRAb) and goiter are risk factors for the relapse of Graves' disease (GD) after the medication of anti‐thyroid drugs (ATDs). The correlation between TRAb and goiter during the development of GD contributes should be elucidated to enhance the cure rate and reduce the relapse rate of GD. The thyroid is a highly vascularized gland. Thyroid blood flow is abundant in GD patients, and angiogenesis exerts a critical role in the formation of goiter. This study aims to explore the role of TRAb in angiogenesis of GD and the underlying mechanism.

Methods: The human thyroid follicular epithelial cell line (Nthy‐ori 3‐1) and human umbilical vein endothelial cells (HUVECs) were induced with the monoclonal thyroid antibody M22 and TSH at varying concentrations. Cell viability, migration and tube formation were assessed by CCK‐8 assay, wound healing assay and tube formation assay, respectively. Protein expressions of TSHR and p‐AKT in M22‐induced HUVECs were measured by Western blotting. Changes in protein expression profiles and relevant signaling pathways in GD specimens were identified by proteomic analysis. Positive expressions of CD34 and PROX1, and their co‐localization in GD specimens and normal thyroid tissues were detected by immunofluorescence assay.

Results: M22 dose‐dependently stimulated the proliferation of Nthy‐ori 3‐1 cells and HUVECs, while an inverted U‐shaped dose‐response curve was displayed by TSH treatment. Both M22 and TSH dose‐dependently stimulated the migration and tube formation of HUVECs. A total of 16 significantly upregulated and 24 downregulated proteins were identified in M22‐induced HUVECs. Among them, the top 1 significantly upregulated protein was PROX1, which was closely linked with angiogenesis. Immunofluorescence assay further validated that PROX1 was significantly upregulated in thyroid tissues collected from GD patients than that of normal thyroid tissues adjacent to papillary thyroid cancer (PTC), which was co‐localized with CD34.

Conclusion: TRAb contributes to angiogenesis by upregulating PROX1 in the formation of goiter in GD patients.

POSTER 203

Autoimmunity Translational Poster

EFFECT OF RAPAMYCIN, MYCOPHENOLIC ACID, OR GLUCOCORTICOIDS ON TH1 AND TH2 CHEMOKINES SECRETION IN RETRO‐ORBITAL CELLS OF PATIENTS WITH GRAVES' OPHTHALMOPATHY

Giusy Elia¹, Francesca Ragusa¹, Sabrina Rosaria Paparo², Valeria Mazzi¹, Armando Patrizio³, Alessandro Antonelli*¹, Silvia Martina Ferrari⁴, Poupak Fallahi²

¹University of Pisa, Department of Surgical, Medical, Molecular Pathology and Critical Area, Italy,²University of Pisa, Department of Translational Research of New Technologies in Medicine and Surgery, Italy,³Department of Emergency Medicine, Azienda Ospedaliero‐Universitaria Pisana, Italy,⁴University of Pisa, Department of Clinical and Experimental Medicine, Italy

Objective: Cytokines and chemokines play crucial roles in the inflammation process of Graves' ophthalmopathy (GO), where they stimulate the T helper (Th)1 and Th2 immune network with the local orbital cells (fibroblasts, preadipocytes and myocytes).

We aim to investigate the effects of rapamycin, mycophenolic acid or glucocorticoids on the synthesis and release of chemokines in GO orbital cells.

Methods: We isolated primary cultures of fibroblasts, preadipocytes and myoblasts from orbits of GO patients, and we tested on them cytokines alone or in combination with increasing concentrations of rapamycin and/or mycophenolic acid and/or glucocorticoids evaluating the secretion of the prototype Th1 [chemokine (C‐X‐C motif) ligand 10 (CXCL10)] and Th2 [chemokine (C‐C motif) ligand 2 (CCL2)] chemokines.

Results: In the retro‐orbital cells of GO we observed that CXCL10, undetectable in the supernatants, was induced by interferon (IFN)‐gamma in a dose‐dependently manner, but not by the tumor necrosis factor (TNF)‐alpha, whereas their combination had a significant synergistic effect on CXCL10 secretion. On the other side, TNF‐alpha dose‐dependently induced CCL2 secretion, which is also at low level in basal condition, whereas IFN‐gamma alone had no effect on it. Again, the combination of TNF‐alpha plus IFN‐gamma elicited a significant synergistic effect on CCL2 release. Adding mycophenolic acid, rapamycin, or glucocorticoids (in a pharmacological range) together with IFN‐gamma and TNF‐alpha stimulation, resulted in a dose‐dependently inhibitory effect on the chemokines release in the retro‐orbital cells of GO. Moreover, the combination of mycophenolic acid with rapamycin and/or with glucocorticoids, have a synergistic inhibitory effect on the release of chemokines.

Conclusion: Our findings showed the therapeutic role of mycophenolic acid or rapamycin and/or glucocorticoids that could be obtained through their immune‐modulatory effect on the Th1 and Th2 chemokines secretion in orbital cells of GO patients.

POSTER 204

Disorders of Thyroid Function Basic Poster

THE ROLE OF AUTOPHAGY THROUGH PI3K/AKT/MTOR PATHWAY IN REGULATING BRAIN DEVELOPMENT OF THE OFFSPRING FROM MATERNAL RATS WITH SUBCLINICAL HYPOTHYROIDISM DURING EARLY PREGNANCY

Wenwen Gao, Xing Qian*

The First Affiliated Hospital of Dalian Medical University, China

Objective: This study aims to investigate whether maternal subclinical hypothyroidism (SCH) influences the level of brain autophagy, brain development and its possible mechanism, and the effect of treatment with levothyroxine (L‐T4) in early maternal SCH on the progeny's developing brain.

Methods: 50 adult female Wistar rats were randomly divided into 5 groups, control group (CON), overt hypothyroidism group (OH), subclinical hypothyroidism group (SCH), subclinical hypothyroidism treatment with L‐T4 group (SCH+L‐T4), and subclinical hypothyroidism treatment with 3‐MA group (SCH +3‐MA). SCH+L‐T4 group was treated with 1.25ug / (100g ·d) L‐T4 from embryonic day 0(E0)to postnatal day 40(P40[1] ).

Results: Autophagosomes were increased, immunofluorescence of LC3B was enhanced, mRNA and protein expressions of LC3B and Beclin 1 were increased, p62 was decreased in brain tissues (E13) of OH and SCH groups, and the escape latency of their offspring was prolonged. At the same time, the mRNA and phosphorylated protein levels of PI3K, AKT and mTOR were decreased in these two groups. The above changes in OH group were more significant than those in SCH group. After administration of 3‐MA, autophagy inhibitor, autophagosome decreased, LC3B, Beclin1mRNA protein and mRNA expression increased in 3MA+SCH group, p62 expression decreased, and escape latency of their offspring recovered. There was no significant difference in molecular expression and escape latency between LT4+SCH group and CON group.

Conclusions: Maternal rats with hypothyroidism and subclinical hypothyroidism in early pregnancy may activate autophagy in the brain tissue of offspring through PI3K/Akt/mTOR signal pathway, resulting in the decline of learning and memory function. Early LT4 therapy is helpful to improve the level of brain autophagy and brain development in offspring.

POSTER 205

Disorders of Thyroid Function Case Study Poster

THYROIDITIS INDUCED BY IMMUNE CHECKPOINT INHIBITOR THERAPY

Luis Medina Mora*, Angelica Sanchez Ruiz, Samihah Ahmed, Edward Merker, Agustin Busta

Lenox Hill Hospital, USA

INTRODUCTION: Immune checkpoint inhibitors (ICI) that target cytotoxic T‐lymphocyte antigen 4 and programmed cell death protein 1 have become an essential part of cancer treatment. ICI is being used with chemotherapy in triple‐negative breast CA (TNBC) resulting in a higher better response rate; however, up to 40% of patients treated with an ICI develop an endocrine adverse event. Approximately 10% of patients develop thyroid toxicity. Although typically manageable, given the non‐specific manifestations and unpredictable timing, the identification of such entities requires a high index of suspicion.

CASE PRESENTATION: A 45‐year‐old female with a recently diagnosed, poorly differentiated triple negative intraductal carcinoma of the left breast with biopsy‐proven metastatic ipsilateral axillary lymph node was started on neoadjuvant chemoimmunotherapy with a combination of paclitaxel, carboplatin, and pembrolizumab. One month after initiating therapy, she started complaining of persistent fatigue and constipation. She was found to have biochemical evidence of hypothyroidism with TSH of 21.8 uIU/mL (reference range: 0.27‐4.20 uIU/mL) and Free T4 of 0.2 ng/dL (reference range: 0.9‐1.8 ng/dL). Thyroid peroxidase antibodies were elevated to 1,634 IU/mL (reference range: ≤34.9 IU/mL). She denied any family history of autoimmune endocrine disorders. A review of the thyroid profile prior to starting ICI was within normal limits. Upon testing, there was no evidence of any other hormonal deficiency. The impression was that she had developed thyroiditis secondary to ICI therapy. Therefore, she was started on levothyroxine supplementation with plans to continue monitoring her thyroid profile while on therapy.

DISCUSSION: The median time of diagnosis of thyroid dysfunction after treatment with an ICI is 6 weeks; however, it can occur as early as 3 weeks. The patients might develop transient thyroiditis from the destruction of thyroid follicular cells, which can progress to hypothyroidism in ∼68% of patients. Typical symptoms include fatigue, weight gain, depression, constipation, and in severe cases, changes in cognitive status. All patients receiving treatment with ICI should be screened with TSH and free T4 every 8 weeks or more frequently if clinically indicated. Thyroid supplementation should be administered as warranted.

POSTER 206

Disorders of Thyroid Function Case Study Poster

METHIMAZOLE INDUCED AGEUSIA IN GRAVES' DISEASE

Erica Jalal*, Rasha Haykal

George Washington University, USA

Introduction: Ageusia and anosmia were observed as minor but rare side effects from methimazole initiation in humans in 1953 but has not been documented since then in the literature. We describe a 58‐year‐old woman who developed ageusia after taking methimazole for Graves' disease treatment.

Case Report: A 58‐year‐old woman presented with a one‐month history of fatigue, insomnia, anorexia, weight loss, abdominal pain, and tremors. She was found to have an undetectable thyroid‐stimulating hormone (TSH), a free thyroxine level (FT4) of >7.77 ng/dL, and positive thyrotropin receptor antibodies (TRAb), confirming a new diagnosis of Graves' disease. Methimazole and propranolol were initiated and after one month, our patient noted that she lost her ability to taste and has a constant metallic taste in her mouth. Methimazole was switched to propylthiouracil (PTU) to address ageusia but was switched back due to nausea and worsening total triiodothyronine (TT3) levels. After nine months of methimazole titration, detectable TSH and normal FT4 and TT3 were achieved, although ageusia persisted.

Discussion: Graves disease treatment is determined by shared decision making on balancing therapeutic control and adverse effects. While methimazole induced ageusia in humans has not been reported since 1953, this medication is a well‐known olfactory toxicant in rodents and is commonly employed in study designs. This case demonstrates that this adverse effect is a non‐life threatening, temporary, and rare adverse effect that can affect treatment planning. Clinicians should be aware of methimazole induced ageusia as it can impact thionamide management of hyperthyroidism and/or thyrotoxicosis.

POSTER 207

Disorders of Thyroid Function Case Study Poster

TEPROTUMUMAB IN EUTHYROID EYE DISEASE AND SUCCESSFUL MANAGEMENT OF DEBILITATING MUSCLE SPASMS

Amira Ibrahim*¹, Tamer Mansour^1,2, Eric Nylen², Shruti Gandhi²

¹George Washington University, USA,²Veterans Affairs Medical Center, USA

Introduction: Teprotumumab is an insulin‐like growth factor 1 receptor (IGF‐1R) inhibiting monoclonal antibody approved for thyroid eye disease (TED). One of its common adverse effects includes mild self‐manageable lower extremity muscle spasms(1). Debilitating upper body myalgias and spasms have not yet been reported nor have their management.

Description: 39‐year‐old African American female presented with a 3‐month history of dry eyes and left eye swelling. Hertel measurements were 19.5 mm (OD) and 23 mm (OS) with 20/20 vision bilaterally. Labs demonstrated elevated antibodies to TSI 384% (normal <140%) and TSH receptor 11.14 IU/L(normal <2IU/L) with normal thyroid function. CT orbits confirmed bilateral proptosis and thickening of the left superior rectus muscle. She was diagnosed with euthyroid ophthalmopathy for which she started selenium. After 4 months, she developed worsened eye pain, diplopia, periorbital edema, worsened visual acuity and her clinical activity score (CAS) was 6/7. She was started on Teprotumumab q3 weeks and despite noting improvement in orbital pain/visual acuity after 4 infusions, she reported severely painful (10/10) muscle aches and upper body spasms (torso and back) starting several days after her second infusion. They occurred sporadically 5 times a week and lasted 15 minutes. These episodes caused several falls and inability to drive. Labs for evaluation were all normal. We advised her to increase her hydration (72 oz water/day) and spaced‐out infusions to q4 weeks, both of which helped mitigate these episodes. After completion of her infusions, her orbital pain, diplopia, and periorbital swelling resolved, and proptosis improved (OS 20mm). Her final CAS was 1/10 and interestingly, her TSI continued to trend downwards to 170%.

Discussion: We report Teprotumumab can cause debilitating upper‐body muscle pain and spasms. While the mechanism is unclear, it may be related to Teprotumumab's antagonism of IGF‐1 on skeletal muscle function, recovery, and muscle mass maintenance(2). We also propose management of this untoward side effect with adequate hydration and consideration of an alternative dosing schedule. Lastly, our case supports the use of TSI as a biomarker of TED activity (3) and suggests its use for therapy response in euthyroid patients.

POSTER 208

Disorders of Thyroid Function Case Study Poster

HYPOTHYROIDISM‐INDUCED REVERSIBLE CARDIOMYOPATHY

Sana Tariq*, Preeti Kishore

Jacobi Medical Center, USA

Introduction: Hypothyroidism may cause several cardiac manifestations including conduction abnormalities, pericardial effusion, decreased myocardial contractility, and accelerated coronary atherosclerosis. Both hypo and hyperthyroidism can cause reversible heart failure. Cardiomyopathy secondary to severe hypothyroidism is a well‐known entity in the elderly population but it has not been well described in the younger population. We are presenting a unique case of severe hypothyroidism‐induced heart failure in a young adult without any known cardiac risk factors.

Case: A 25‐year‐old man with hypothyroidism (diagnosed at the age of 10 years), untreated lupus, pulmonary tuberculosis (not on any treatment) and CKD III presented with foot pain, fever, myalgias, and swelling of lower extremities. Vital signs BP 119/72, pulse 75, temp 100.8 °F, RR 16. Physical exam was significant for a thin cachectic man with tenderness in bilateral lower extremities, cardio pulmonary exam was unremarkable.

Initial blood work revealed white cell count of 5.7k/uL (4.8–10.8 k/uL), hemoglobin 7.7 g/L (10‐14 g/dl), and platelet count 217/uL (150–440 k/uL). Thyroid function tests revealed thyroid‐stimulating hormone >100 uU/ml (0.4–4.20 uU/ml), free T4 < 0.4 ng/dL (0.6–1.5). The antithyroid peroxidase antibody titer was 2.3 IU/mL (<5.0). Serum chemistry showed sodium 141 (135–145) mEq/L, potassium 3.9 (3.5–5.0) mEq/L, chloride 113 (98–108) mEq/L, bicarbonate 23 (24–30) mEq/L, blood urea nitrogen 16 (5–20) mg/dL, creatinine 2.17 (0.1–1.5) mg/dL, troponin I < 0.01(<0.03) ng/L, cortisol 13.8 (4–20) μg/dL.

Transthoracic echocardiography (TTE) showed diffuse hypokinesis, severely decreased left ventricular ejection fraction of 30%, and moderate pericardial effusion without any evidence of tamponade. Anti‐TPO was negative but the most likely diagnosis was antibody‐negative Hashimoto thyroiditis. The patient was started on oral levothyroxine 75 mcg daily. As per cardiology recommendations patient was treated only with levothyroxine and GDMT was not initiated. On follow‐up TTE after one week there was a significant improvement in LV function and EF improved from 30% to 45%. On the day of discharge, his FT4 was 0.6.

Discussion: Here we describe a case of rapidly reversible heart failure attributed to severe hypothyroidism in a young man without any other cardiac risk factors. Hypothyroidism can easily be overlooked during the diagnostic work‐up as a rare cause of reversible heart failure. Early recognition and initiation of replacement therapy is an important tool in the management of hypothyroidism‐associated heart failure.

POSTER 209

Disorders of Thyroid Function Translational Poster

BRINGING 4P MEDICINE TO TREATMENT OF HYPOTHYROIDISM THROUGH A VIRTUAL COMPREHENSIVE CARE HELPS WITH NORMALIZING THYROID HORMONE VALUES, WEIGHT NORMALIZATION AND IMPROVED QOL

Vedrana Högqvist Tabor, Marina Tarasova*, Guillaume Cohen‐Skalli, Florian Dubois, Brittany Curran

Butterfly Technologies Inc, USA

Hypothyroidism affects 20 million Americans, and despite hormone replacement being the standard treatment, many still suffer from poor quality of life (QoL) and are dissatisfied with their current therapy. Holistic treatment for hypothyroidism is lacking in today's healthcare system, which can lead to health complications such as diabetes, depression, and heart conditions.

We used current technology to create a P4 medicine approach (predictive, preventive, personalized and participative) to provide the best individual care for hypothyroid patients, enabling them to access hypothyroid care from the comfort of their home. The Paloma Health Thyroid Solution consists of a virtual clinic providing holistic thyroid care and a robust patient app. This solution enables patients to (i) receive care from experienced MDs, (ii) test their thyroid hormone levels; (iii) record their symptoms daily; (iv) access a library of informational articles, and (v) connect to a community of hypothyroid patients, all of that from the comfort of own home.

At the start of treatment, we use proprietary algorithms to determine the best fitting therapy. During the first three months, patients have access to a 12‐week program that teaches them the most important aspects of self‐managing hypothyroidism. In addition, we developed electronic tools enabling patients to convey all the relevant information about their condition to their HCP.

In order to evaluate the usefulness of the approach, we followed 502 hypothyroid patients for 6 months, capturing patients' symptoms and combining them with the biochemical and weight data. The majority of patients significantly improved their symptoms, such as energy, focus, and sensitivity to cold, as well as their QoL, starting at 4 weeks. Additionally, 48% of overweight or obese patients showed a significant reduction in BMI, and normalization of their TSH values. These improvements continued throughout the entire observation period. Finally, we collected data on patient satisfaction with the management of hypothyroidism and observed a significant increase in satisfaction rates.

Here we show for the first time that using the 4P approach has the potential to help patients normalize their lab values, weight and remaining symptoms of hypothyroidism.

POSTER 210

History of Thyroid Translational Poster

FEARS OF LEVOTHYROXINE ACCESS LOSS WITHIN THE CULTURAL ZEITGEIST: A QUALITATIVE SURVEY OF POST‐APOCALYPTIC FICTION

Sean Wrenn, Jordan Williamson*

Rush University Medical Center, USA

Objective: One potential source of concern amongst patients with acquired hypothyroidism, or considering thyroidectomy, is the permanent reliance on a medication such as exogenous levothyroxine (LT4). Fears about availability, affordability, and access may drive patient‐level decision making. While access to LT4, a World Health Organization essential medicine, is rarely difficult, potential disruptions to supply chains, governmental dysfunction, or economic collapse could pose threats to reliant patients. This fear is embodied in post‐apocalyptic fiction (PAF) media. PAF is a popular genre producing numerous works conveying similar tropes and themes‐ ultimately influencing societal perceptions about real‐world issues such as medication scarcity.

Methods: A comprehensive internet‐based literature review of the PAF subgenre was performed with assistance of a language model ChatGPT, based on GPT‐3.5 architecture and trained by OpenAI. The author verified and reviewed the sourced individual materials manually. Characters with hypothyroidism were studied within the realm of PAF qualitatively to assess their hypothetical clinical outcomes and quality of life. Potential cultural impact of each storyline was measured using available data on box office revenue, Nielsen viewership, or Nielsen BookScan.

Results: Three PAF works were noted explicitly containing a LT4‐dependent character. Cormac McCarthy's novel The Road (2006) features a nameless elderly character (encountered by the protagonist) with hypothyroidism and issues accessing LT4. The character ultimately dies of starvation, exposure, and presumed hypothyroidism. Another character in the 2010 movie The Book of Eli, played by Tom Waits and named The Engineer, is seen ingesting levothyroxine. It is implied that The Engineer has issues accessing this medication. The television series The Walking Dead (2010‐2022) featured a character named Eugene Porter whom is revealed to rely on levothyroxine. While Eugene suffers significant medical issues, he does not apparently endure clinical hypothyroidism or lose medication access.

Discussion: While LT4 remains abundant and accessible within the developed world, patients continue to have justifiable fears about long‐term access. Fears can stem from, or be reflected within, numerous notable cultural works in the genre of PAF. These can help bring awareness to the issue of medication access and demonstrate how the cultural zeitgeist might impact clinical decision making.

POSTER 211

Disorders of Thyroid Function Clinical Poster

HIGH SERUM REVERSE T3 LEVEL IS BIOMARKER OF POST‐COVID‐19 DEPRESSION: A PROSPECTIVE COHORT STUDY

Fabyan Beltrão¹, Daniele Beltrão², Giulia Carvalhal³, Fabricia Beltrão⁴, Fabio Hecht⁵, Maria da Conceição Gonçalves⁶, Helton Ramos*⁷

¹Federal University of Paraiba, Lauro Wanderley University Hospital, Department of Endocrinology, Brazil,²Faculty of Medical Sciences of Paraíba, Department of Medicine, Brazil,³Center for Biological and Health Sciences, Federal university of Campina Grande, Brazil,⁴Faculty of Medical Sciences of Paraíba, Department of Medicine, Brazil,⁵The Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil,⁶Post‐Graduation Program in Nutritional Sciences, Department of Nutrition, Center for Health Sciences, Federal University of Paraíba, Brazil,⁷Department of Bioregulation, Federal University of Bahia, Brazil

Introduction: Neuropsychiatric complications in COVID‐19 survivors are poorly understood. COVID‐19 appears to be associated with a broad spectrum of neuropsychiatric manifestations, including depressive symptoms, psychoses and post‐traumatic stress disorder. We aim to analyze the influence of biological parameters (mainly thyroid function) recorded in the first 48 hours of hospital admission on neuropsychological (depressive symptoms) changes in patients with moderate to severe SARS‐CoV‐2 infection after discharge.

Methods: In this prospective cohort study, between June and August 2020, we collected laboratory [thyroid function (TSH, free T3, free T4 and reverse T3), vitamin D, inflammatory biomarkers, and hematologic indices) from 273 hospitalized patients with COVID‐19. After hospital discharge, 74 patients were followed up for 30 – 45 days. We divided them into depressive (28) and non‐depressive (46), based on a score on the Beck Depression Inventory (score >9).

Results: 74 patients were stratified. In multivariate logistic regression (corrected by comorbidities), the biomarkers represented related independent risk factors for depression post‐COVID‐19: age >56 years (OR 5.63, p = 0.007); D‐dimer >730 ng/mL (OR 5.52 p = 0.002); Reverse T3 > 0.75 (OR 3.88, p = 0.03), Hemoglobin <13.4 g/dL (OR 3.86, p = 0.011); RDW >13.6% (OR 3.57, p = 0.018), and 25‐OH vitamin D < 25 (OR 3.11, p = 0.026). Regarding the other tests of thyroid function (fT4, fT3, and TSH) and biomarkers (IL‐6, CRP, neutrophils) there was no difference between the groups.

Conclusion: Biological markers obtained during hospitalization, such as serum reverse T3 levels, may serve as predictors for post‐COVID‐19 depression symptoms occurring two months after the acute phase of the illness.

POSTER 212

Disorders of Thyroid Function Clinical Poster

THE IMPACT OF HYPOTHYROIDISM ON CARDIOVASCULAR‐ASSOCIATED HEALTHCARE UTILIZATION IN THE US POPULATION WITH DIABETES

Matthew Ettleson*, Gustavo Penna, Wen Wan, Neda Laiteerapong, Antonio Bianco

University of Chicago, USA

Objective: Suboptimal treatment of hypothyroidism (HT) is associated with adverse cardiovascular (CV) outcomes, for which patients with diabetes are at increased risk. The primary objective of this study was to compare healthcare utilization outcomes (e.g., healthcare visits, specialty care, and medications) associated with CV disease in DM patients with and without HT.

Methods: Participant data was collected from the Medical Expenditure Panel Survey (MEPS) over 10 years (2011 – 2020). Participant weights were used to estimate trends in the US population with DM. Medical conditions were identified by ICD‐9/ICD‐10 codes associated with expenditures. Healthcare utilization outcomes included number of emergency, hospital, and outpatient visits associated with coronary heart disease (CHD), stroke, or heart failure (HF), prescriptions related to CV outcomes, and number of visits to specialty providers. In a secondary analysis, to account for sociodemographic and clinical differences between those with and without HT, a propensity score‐based fine stratification matching approach was used to determine the relative risk (RR) of CV‐related utilization outcomes associated with HT.

Results: A total of 15,294 adult participants with DM were identified, representing a population of approximately 14.1 million US adults, of which 1.7 million (11.8%) had HT. In the weighted analysis, a significantly greater proportion of participants with HT had CHD and stroke‐associated visits compared to those without HT (22.4% vs 17.8%, p = 0.001; and 7.3% vs 5.4%, p = 0.012). Rates of HF‐associated visits were similar between the two groups (3.4% vs 2.7%, p = 0.267). In the matched analysis, the RR of a stroke‐associated event was significantly higher in the HT group (RR = 1.28, 95% CI [1.03 – 1.59], p = 0.024), but the RR of CHD and HF‐associated events were not significantly different between the two groups. In the matched analysis, participants with HT were more likely to have a visit with a specialist (cardiology, endocrinology, neurology, and nephrology). Participants with HT were more likely to be treated with cholesterol‐lowering medications, SGLT‐2 inhibitors, and diuretics, but not GLP‐1 agonists, ACE inhibitors or anti‐platelet agents.

Conclusion: HT as a comorbidity with DM was associated with increased healthcare utilization related to cardiovascular diseases, specifically visits associated with stroke, specialty care, and the use of diuretics (including SGLT‐2 inhibitors) and cholesterol‐lowering medications.

POSTER 213

Disorders of Thyroid Function Clinical Poster

PHARMACODYNAMIC RESPONSES TO VRDN‐001, A FULL ANTAGONIST ANTIBODY TO IGF‐1 RECEPTOR IN DEVELOPMENT FOR THYROID EYE DISEASE (TED) IN HEALTHY VOLUNTEERS AND PATIENTS WITH ACTIVE TED

Kelly Foster*, Brent Dickinson, Rochelle Summerfelt, Angela She, Barrett Katz

Viridian Therapeutics, USA

Objective: VRDN‐001, a full antagonist antibody to IGF‐1 receptor (IGF‐1R), is in development for the treatment of thyroid eye disease (TED). Clinical and preclinical evidence demonstrate IGF‐1R antagonism reduces the inflammation and proptosis that occur in TED. We provide pharmacodynamic (PD) results in healthy volunteers and TED patients from our ongoing phase 1/2/3 clinical trial (NCT05176639) evaluating VRDN‐001.

Methods: Healthy volunteers (HVs) and patients with active, moderate‐to‐severe TED were randomized 3:1 to receive 2 intravenous infusions 3 weeks apart of either 3, 10, or 20 mg/kg VRDN‐001 or placebo. PD parameters (IGF‐1 serum levels) were assessed through 7 weeks.

Results: Thirteen HVs received either placebo (n = 3) or VRDN‐001, 3 mg/kg (n = 3), 10 mg/kg (n = 3), or 20 mg/kg (n = 4). Twenty‐seven TED patients received either placebo (n = 6) or VRDN‐001, 3 mg/kg (n = 9), 10 mg/kg (n = 6), or 20 mg/kg (n = 6). One placebo patient was withdrawn prior to the 6‐week visit because of protocol deviation. Baseline characteristics were similar across all TED cohorts. All VRDN‐001 doses elicited rapid, sustained, and similar increases in IGF‐1 serum levels, a biomarker for target engagement and IGF‐1R inhibition. In HVs receiving VRDN‐001 (n = 10), IGF‐1 serum levels increased within a day of the first infusion for all doses, reaching 4–6‐fold above baseline; levels continued to increase after the second infusion, ultimately reaching 4–9‐fold above baseline. In TED patients receiving VRDN‐001 (n = 21), IGF‐1 serum levels increased for all doses 2–6‐fold above baseline after the first infusion, and further increased after the second infusion, ultimately reaching 2–9‐fold above baseline. No increases in IGF‐1 serum levels occurred in HVs and TED patients receiving placebo.

Discussion/Conclusion: Two infusions of VRDN‐001 in healthy volunteers as well as TED patients elicited rapid and sustained increases in IGF‐1 serum levels that were similar across groups, indicating maximal target engagement at all doses tested. Results from the ongoing THRIVE phase 3 trial will further inform VRDN‐001 potential treatment regimens that balance efficacy and treatment burden in TED.

POSTER 214

Disorders of Thyroid Function Clinical Poster

WHICH IS THE BEST TREATMENT TO MANAGE RELAPSED GRAVES' DISEASE PATIENTS: CONTINUOUS USE OF LOW‐DOSE OF METHIMAZOLE, A SECOND COURSE OF METHIMAZOLE, OR RADIOIODINE THERAPY?

Danilo Villagelin*^1,2,3, Juliana Andrade^3,4, Roberto Santos^1,2, Nicolas Perini², Joao Romaldini¹

¹Endocrinology and Metabology, Pontifical Catholic University of Campinas, Brazil,²Endocrinology and Metabology, Hospital PUCCampinas, Brazil,³Postgraduate Course Internal Medicine, Unicamp, Brazil,⁴San Francisco University, Brazil

Objective: Evaluated the results of Graves' disease (GD) relapsed patients managed with radioiodine plus levothyroxine (RAI+LT4), continuous use of methimazole (cMMI), and a second course of MMI (scMMI).

Methods: We evaluated 330 patients (age: 45.65 ± 13.63 years) after MMI were discontinued (18‐24 months), and 164 (49%) patients relapsed. The group RAI+LT4 consisted of 40 patients, (45.38 ± 13.93 years), follow‐up of 120 ± 76.17 months. cMMI group included 49 patients (45.59 ± 13.46) treated with cMMI (median dose 5 mg;1‐7 mg) for 78.04 ± 45.41 months. scMMI group included 75 patients (45.84 ± 13.76 years) receiving scMMI for 57.78 ± 47.75 months, and MMI dose was tapered and discontinued when TRAb became undetectable.

Results: In the RAI+LT4 group: 87.5% were female, mean TSH and free T4 at diagnosis were 0.02 ± 0.08 and 3.98 ± 2.01 respectively, mean clinical activity score (CAS) at diagnosis was 0.93 ± 1.42, and 35% were smoking. TPOAb, TgAb, and TRAb assays were positive in 65.6%, 46.7%, and 89.3%, respectively. cMMI group: 77.6% were female, and mean TSH and free T4 at diagnosis were 0.02 ± 0.04 and 3.87 ± 2.32 respectively. GD patients showed a mean CAS of 0.73 ± 1.11 and 28.6% were smoking. TPOAb, TgAb, and TRAb were positive in 59.1%, 41.9%, and 83.7%, respectively. scMMI group: 88% were female, mean TSH and free T4 at diagnosis were 0.01 ± 0.03 and 3.98 ± 2.35 respectively, and mean CAS were 0.54 ± 1.16 and 30.7% were smoking. TPOAb, TgAb, and TRAb were positive in 71.6%; 42.6%, and 79.4%, respectively. After a negative TRAb result, MMI was discontinued. Then, within a period of 13.04 ± 11.56 months, 42% of patients relapsed. There were no statistical differences in initial TSH, free T4, age, CAS, and thyroid antibodies. The remission rate of scMMI of 58.7% was slightly higher than the first course of MMI treatment (51%). Euthyroidism rates were more frequent in cMMI (77,6%) compared with RAI+LT4 (50%) and scMMI groups (59%) (p < 0,001).

Conclusion: Our study showed that GD patients who maintain the scheme of continuous MMI obtained greater benefits regarding the control of thyroid function compared with RAI+LT4 and a second course of MMI.

POSTER 215

Disorders of Thyroid Function Clinical Poster

VALIDATION OF THYROID INTERPRETER, A MOBILE APPLICATION‐BASED TOOL IN THE DIAGNOSIS AND MANAGEMENT OF THYROID DISORDERS IN PEDIATRIC AND ADULT POPULATIONS

Vibha Yadav*, Dhvani Raithatha, Manoj Agarwal

Regency,CDER, India

Background: Thyroid function tests are the most performed endocrine test indicated in various disorders. Appropriate assessment is essential for the timely diagnosis and management of these disorders. Lack of access to specialist endocrine care makes interpretation of thyroid function tests in resource‐poor settings. There is a need to develop a point‐of‐care tool for guidance on thyroid function interpretation.

Aim: To develop and validate Thyroid Interpreter, a point of care tool for interpreting thyroid functions.

Methods: The Thyroid interpreter interprets thyroid functions following input of key parameters (age, total or Free T4, and TSH), guiding further evaluation and management. The guidance provided by the Thyroid interpreter was validated against expert management in children and adults presenting to the Endocrine Clinic of our hospital from January 2020‐February 2023.

Results: The Thyroid interpreter was validated in 534 children and adults. Thyroid disorders included acquired hypothyroidism (n = 144), subclinical hypothyroidism (n = 69), congenital hypothyroidism (n = 54), thyrotoxicosis (n = 42), and central hypothyroidism (n = 30). Euthyroid status was found in 195 subjects. Thyroid interpreter was concordant with expert opinion diagnosis in 530 (99.3%) cases with discordance in four (diagnosis of central hypothyroidism in two with primary hypothyroidism and normal neonatal screening in two due to delayed TSH rise).

Conclusion: Our Thyroid interpreter has high accuracy in guiding the management of thyroid disorders while limiting the extent of exhaustive workup.

POSTER 216

Disorders of Thyroid Function Clinical Poster

ULTRASOUND‐GUIDED MICROWAVE ABLATION FOR PERSISTENT OR RELAPSED GRAVES' HYPERTHYROIDISM: A PRELIMINARY STUDY

Ying Chen, Shuhang Xu*, Chao Liu

Nanjing University of Chinese Medicine, China

Objectives: To explore the efficacy and safety of ultrasound‐guided microwave ablation (MWA) on persistent or relapsed Graves' hyperthyroidism, and the influence of the postoperative treatment of rituximab (RTX) on therapeutic outcomes of MWA.

Methods: A total of 18 patients with persistent or relapsed Graves' hyperthyroidism treated with MWA from March 2019 to January 2022 were recruited. These patients were divided into two groups according to whether having received postoperative RTX. Baseline characteristics were recorded. In addition, the thyroid function, thyroid volume and dosage of antithyroid drug (ATD) at baseline and after MWA were compared. The withdrawal rate of ATD after MWA was calculated. Adverse events in both groups were recorded as well. Factors influencing postoperative dosage of ATD were explored by the multiple linear regression model.

Results: A total of 18 patients with persistent or relapsed Graves' hyperthyroidism were recruited, including 17 women and 1 man with a mean age of 31.44 ± 11.90 years and a follow‐up period of 16.00 (6.50, 24.00) months. The Free triiodothyronine (FT3) (6.60 (4.76, 8.51) pmol/l vs. 4.88 (4.48, 5.73) pmol/l, P = 0.031), thyrotrophin receptor antibody (TRAb) (11.86 (8.53, 19.78) IU/l vs. 3.15 (2.11, 6.98) IU/l, P = 0.004) and thyroid stimulating immunoglobulin (TSI) (9.99 (7.27, 16.95) IU/l vs. 2.58 (1.37, 5.12) IU/l, P = 0.002) at the last follow‐up visit were significantly reduced, compared with preoperative values, so as the thyroid volume (33.87 (20.20, 57.90) vs. 24.70 (16.91, 45.29) ml, P = 0.004). The mean dosage of ATD at the last follow‐up visit was 3.81 ± 3.92 mg/d, significantly lower than that before MWA (13.40 ± 7.40 mg/d, P < 0.001). Patients intervened with postoperative RTX after MWA presented a better thyroid function. The multiple linear regression analysis showed that the dosage of ATD at the last follow‐up visit was significantly correlated with the follow‐up time, baseline TRAb and baseline TSI. The withdrawal of ATD until the last follow‐up visit was observed in 5 patients, with a total withdrawal rate of 27.78%. No severe adverse events after MWA and postoperative treatment of RTX were reported.

Conclusion: Ultrasound‐guided MWA significantly shrinks the thyroid volume and reduces ATD dosage with an acceptable safety. Some patients can even achieve the withdrawal of ATD. Postoperative RTX after MWA effectively reduces TRAb level, which is favorable to the withdrawal of ATD.

POSTER 217

Disorders of Thyroid Function Clinical Poster

EFFECT OF RIFAMPIN ON LEVOTHYROXINE REPLACEMENT IN HYPOTHYROIDISM

Farah Kitana*, Dmitriy Stasishin, Deema Al‐Souri, Meeta Sharma

Medstar washington hospital Center, USA

Introduction: Rifampin is often used to treat tuberculosis and is a potent inducer of cytochrome P450 (CYP) enzymes and transporters. This causes many well‐known clinically significant drug‐drug interactions. Here we report a case of a patient with post‐surgical hypothyroidism who was on replacement therapy with levothyroxine. She became uncontrolled after starting rifampin therapy, requiring a 70% increase in her levothyroxine dosage.

Description of the Case: A 58‐year‐old Female with a past medical history of gastric bypass and post‐surgical hypothyroidism was treated with a stable dose of levothyroxine 88mcg orally once daily. The patient was started on rifampin therapy for tuberculosis, confirmed by positive QuantiFERON test and a sputum culture containing AFB. Two months after starting rifampin, the patient was admitted for pulmonary embolism. During that admission she reported having symptoms of hypothyroidism such as cold intolerance, fatigue, and myalgias. Subsequently, thyroid function tests were sent and she was found to have a 6‐fold increase in the TSH level (from a baseline of 8.5. to 57.5) and 28% decrease in freeT4 levels (from a baseline of 1.2 to 0.87) despite compliance with levothyroxine therapy. Her levothyroxine dose was progressively increased to 150mcg orally once daily with remarkable improvement in her symptoms and normalization of the TSH level.

Discussion: There have been a handful of cases describing the effect of rifampin on hypothyroidism and the need for levothyroxine dose adjustment. This case reflects the significant impact of rifampin therapy on levothyroxine dose requirements. Close monitoring and subsequent dose adjustment of levothyroxine is crucial especially in the context of post‐surgical hypothyroidism to prevent the development of severe hypothyroidism and myxedema.

POSTER 218

Pediatrics Case Study Poster

IODINE DEFICIENCY HYPOTHYROIDISM IN CHILDREN IN RECENT YEARS

Tejal Patel*¹, Nadia Merchant^1,2

¹Children's National Hospital, USA,²GWU, USA

Objective: Iodine deficiency is a leading cause of hypothyroidism worldwide. It has been nearly eliminated in developed countries after fortification of foods with iodized salt. However, iodine nutrition has become a growing issue within the United States due to new dietary patterns. Younger children may be severely impacted as thyroid hormone is important for growth and brain development. There are no recent studies looking at the current state of iodine deficiency. We aim to look at our population of children at a freestanding academic children's hospital with iodine deficiency hypothyroidism to gain more insight.

Methods: We performed retrospective chart review based on ICD codes (thyromegaly, iodine related thyroid disorder, and iodine deficiency hypothyroidism) of children at our outpatient endocrine clinics from 1/1/2015‐2/28/2023. Fifty charts were reviewed and four met criteria. We excluded 16 for autoimmune thyroid disease, 8 for inability to diagnose iodine deficiency despite presentation of thyromegaly and negative antibodies, and 22 for other reasons. The primary outcome was low urine iodine level to confirm diagnosis. We further characterized severity of disease, risk factors, goiter, thyroid labs and antibodies.

Results: All cases had significant goiter and were diagnosed within the last two years. Case 1: 5‐year‐old male with history of developmental delay and multiple food allergies had severe iodine deficiency hypothyroidism due to no iodized salt intake. Case 2: 5‐year‐old male had moderate iodine deficiency with subclinical hypothyroidism due to non‐iodized salt intake. Case 3: 12‐year‐old female had moderate iodine deficiency hypothyroidism due to restrictive diet and non‐iodized salt intake with two positive thyroid antibodies. Case 4: 12‐year‐old female had mild iodine deficiency hypothyroidism due to non‐iodized salt intake and no processed foods use with one positive thyroid antibody.

Discussion: There has been a decline in iodine status since the 1970s. In our cohort, two children had autoimmune hypothyroidism with iodine deficiency due to non‐iodized salt intake. It is critical to take a dietary history and inquire about the type of salt to ensure there is no underlying contributing iodine deficiency in those with autoimmunity. Current trends need to be assessed nationally to determine if preventative health measures need to be reevaluated.

POSTER 219

Pediatrics Clinical Poster

IMPLEMENTATION OF A POWER BI DASHBOARD TO IMPROVE CARE FOR PATIENTS WITH CONGENITAL HYPOTHYROIDISM: A QUALITY IMPROVEMENT PROJECT

Rob Gonsalves*, Linda Black, Vinay Vaidya, Pierina Ortiz, Chirag Kapadia

Phoenix Children's, USA

Objective: Aim Statement: To increase the percentage of patients with congenital hypothyroidism (CH) age 3 months to 3 years with 2 or more normal thyroid stimulating hormone (TSH) values from 75% in 2021 to over 90% in 2022. Our secondary aim was to ensure all patients identified with the dashboard had a follow‐up appointment scheduled.

Methods: We developed a Power BI data gathering dashboard designed to pull data from our electronic medical record (EMR) system to identify CH patients with the age range specified above. Searchable data within the dashboard included number of clinic visits, date of last clinic visit, time until next clinic visit, and TSH lab values. It also displayed a one‐year total and year‐to‐date list of our primary outcome, allowing us to track progress in real time.

An endocrine nurse reviewed the dashboard weekly and directed efforts toward patients with less than 2 normal TSH values and/or less than 2 visits over the past year. Efforts included placing and communicating lab orders with patients, as well as communicating lab results, dose adjustments, and appointment needs with the primary endocrine provider. We continued to reach out to patients who did not respond to initial requests. A text‐messaging feature built into our EMR that also included an electronic scheduling link aided with communication and scheduling.

Results: At the completion of 2022, there were 91 patients with CH at the age range specified above with 2 or more clinic visits. 83 patients (91%) had at least 2 normal TSH values by the end of 2022. Of the 8 patients who did not, 5 had persistently elevated TSH requiring dose adjustments and 3 neglected to get labs done. Follow‐up was arranged for the 11 patients with only 1 visit in 2022.

Discussion: Implementation of a dashboard within our EMR greatly improved our ability to track patient outcomes and lead to a significant increase in the percentage of patients with 2 or more normal TSH values in 2022. Having a nurse act as a liaison between patients and their primary endocrinologist helped overcome the logistical challenges of a condition that requires frequent lab draws and follow‐up.

We achieved both our aims for 2022, and for 2023 hope to increase to over 95%.

POSTER 220

Pediatrics Clinical Poster

PEDIATRIC GRAVES' DISEASE: IMPROVEMENT OF FREE T4 IN NEWLY DIAGNOSED PATIENTS THROUGH A MULTIFACETED QUALITY IMPROVEMENT APPROACH

Einas Alkhatib*¹, Tejal Patel¹, Julie Harlam¹, Andrew Dauber^1,2, Priya Vaidyanathan^1,2

¹Children's National Hospital, USA,²George Washington University, USA

Objectives: There is limited literature on the treatment course for newly diagnosed Pediatric Graves' disease. The first‐line treatment is antithyroid medication, methimazole. While it takes 3 to 4 weeks for symptom improvement, there is no literature data on time to reach euthyroid state after starting methimazole. At our institution, only 47% of patients achieved a normal free thyroxine (FT4) level within a three‐month timeframe. Through a multifaceted quality improvement approach, we aimed to increase our percentage of newly diagnosed Graves' patients with a normal FT4 from 47% to 85%.

Methods: An electronic thyroid dashboard was used to keep track of new Graves' patients. Using standard quality improvement methodologies, we identified education, medication dosing, and timely reassessments as our limitations. Our first PDSA cycle included an educational handout with a checklist, a standardized methimazole dose of 0.5 mg/kg (max 30 mg daily), provider check‐ins at two weeks, and telehealth appointments at four weeks with repeat labs. Our second PDSA cycle included modification to the Spanish version of the checklist. We compared results to pre‐intervention data from the thirty patients diagnosed in the previous year.

Results: Ten patients completed 3 months post‐intervention thus far. 89% of patients received written education (vs. 45% pre‐intervention). 90% were initiated on the standardized 0.5 mg/kg/day methimazole dose, whereas pre‐intervention doses were not standardized and ranged between 0.1 and 0.75 mg/kg/day. 90% participated in the two‐week phone check in; 90% attended the one‐month telehealth visit. 100% obtained labs after one month (vs.70%). By 3 months, 90% of patients have attained a normal FT4 level, compared to 47% pre‐intervention.

Discussion/Conclusion: A multifaceted QI approach of providing handouts, standardizing initial methimazole dose, and having consistent provider check‐in has increased our percentage of newly diagnosed Graves' disease patients with a normal FT4 from 47% to 90%. Attaining a normal FT4 earlier on is crucial in improving symptoms, quality of life, and potentially long‐term disease patterns. Limitations include a small sample size thus far; however, future directions include continuing to apply this QI approach to all new pediatric Graves' disease patients and extending the period of follow up.

POSTER 221

Pregnancy and Development Clinical Poster

MATERNAL HYPOTHYROXINEMIA IN THE FIRST TRIMESTER AND CHILD'S BEHAVIORS AND COGNITIVE ABILITIES : A PROSPECTIVE INTERVENTION STUDY

Yutong Han*¹, Aihua Liu², Chenyan Li¹, Weiping Teng¹, Zhongyan Shan¹

¹The First Hospital of China Medical University, China,²Peking University Third Hospital, China

Objective: Maternal isolated hypothyroxinemia(IH) in pregnancy has been associated with poor mental development in offspring, but there is no conclusive evidence. This study investigated the association between IH in the first trimester and mental development in children and examined the effects of levothyroxine (LT4) treatment.

Methods: This was a prospective cohort study. Women were screened for thyroid function during the first 8 weeks of pregnancy. IH was defined as normal TSH levels and FT4 < 10th. Severe IH was defined when FT4 was <5th percentile. Pregnant women diagnosed with IH were randomised to treatment group and observation group, and LT4 dose was adjusted to ensure normal thyroid function levels during pregnancy. Children's behavioral and psychiatric development was assessed in their offspring at 2‐3 years of age using the CBCL2‐3 scale and at 5‐6 years of age using the SRS and ABC scales.

Results: A total of 147 mother‐child pairs were included in this study, 51 in the IH group and 42 in the LT4 treatment group. Results from the CBCL scale showed that offspring with IH were significantly more likely to have higher withdrawal, depression, aggression, and disruption scores and higher total T scores than control group (p < 0.05). There were no significant differences between the treatment and control groups. Results from the SRS scale showed significantly higher scores for social awareness, social cognition, social communication, social motivation and total scores in offspring with IH (p < 0.05). Results from the ABC scale showed significantly higher scores for language skills, self‐care and total scores in offspring with IH (p < 0.05). After full adjustment, in male offspring, IH was significantly associated with an increased risk of behavioral problems (OR = 29.55,95% CI: 2.98‐292.97,p = 0.004) and a positive primary screening for autism (OR = 17.74,95% CI: 1.26‐250.24,p = 0.033). The treatment group was not associated with the occurrence of behavioral risk. In female offspring, the groups were not significantly associated with the occurrence of behavioral problem risk.

Conclusions: There were more cognitive and behavioral problems in the offspring with hypothyroxinemia, more pronounced in the male offspring. Treatment with LT4 given early in pregnancy may improve behavioral problems to some extent.

POSTER 222

Surgery Case Study

DERMOID IN THYROID REGION: PROBABLY 1ST CASE IN LITERATURE IN PEDIATRIC AGE

dr sambhaji chintale*

cosmo ent superspeciality hospital and research center chatrapati sambhaji nagar, India

ABSTRACT:

Dermoid cysts are the most common teratomatous lesion; however, they infrequently arise in the head and neck region. Very rarely, dermoid cysts have been described in the thyroid region, masquerading as a thyroid nodule. We describe the case of a 9‐year‐old female child having anterior neck swelling on left side of neck, which was excised and histopathology report found to be a dermoid cyst.

AIM: To know the rare care presentation in thyroid region

METHOD: This is 9 yr old female child presented with neck swelling to our ENT DEPT OPD

We evaluated thoroughly with all routine blood investigation including thyroid profile .USG neck, FNAC and histopathology suggested as dermoid cyst of thyroid region

RESULTS: We operated this case under general anaesthesia taking horizontal skin crease incision. Strap muscle retracted, swelling was present behind the left lobe of thyroid we dissected and removal done in total

CONCLUSION: There are lots of site for dermoid cyst permeation usually in neck in midline But this was typical case presented in thyroid region giving totally looks like thyroid swelling misleading for thyroid diseases. So it was rare finding to know about such site of dermoid in thyroid region to all our clinician and general physician in medical science we reported this case for our knowledge gain

POSTER 223

Surgery Clinical

INVESTIGATION AND CHARACTERIZATION OF THE CURRENT STATUS, DEVELOPMENT AND PROSPECT OF ENERGY‐BASED DEVICES APPLICATION IN THYROID SURGERY: A BIBLIOMETRIC ANALYSIS

Chenyi Wang*

People Hospital of Peking University, China

Objective: New energy‐based devices such as LigaSure vessel sealing system, harmonic scalpel, and other hemostatic techniques are often employed in thyroid surgery in the effort to reduce operating time and complications. Although thyroidectomy is one of the most common surgical procedures, the safest, most efficient, and cost‐effective way to achieve hemostasis is hotly debated. The aim of this study is to comprehensive understanding of the profile of the research status and determination of novel directions in energy‐based devices application in thyroid surgery.

Methods: The Web of Science Core Collection (WOSCC) dataset was queried to collect all relevant publications related to energy‐based devices application in Thyroid Surgery on April 1, 2022. Bibliometric analyses of the acquired data were conducted with CiteSpace and VOSviewer software on these publications, to evaluate the collaborations among different countries, institutions and authors, as well as to explore the current hotspots and future directions in this field.

Results: Ultimately, we identified and analyzed a total of 217 records in English. There was a noticeable increase in publications since 2000s. The Italy contributed to almost a quarter of the records included with a leading position, followed by the United States (35 publications), China (23 publications), Turkey (21 publications) and South Korea (18 publications). The universities and institutes from Italy and Korea such as Naples University, Insubria University, Korea University were the biggest nodes in every cluster of the collaboration network. Active collaborations among the countries were observed. As for the productive authors, Dionigi, G featured the highest number of publications among all authors (17 documents), and he also had the highest average citations (287 times). Keywords co‐occurrence analysis divided the energy‐based devices application in thyroid surgery studies into 6 clusters: bipolar thermofusion vessel, sutureless technique, continuous intraoperative neuromonitoring, hemostatic device, covidien ligasure Maryland jaw, cold knife dissection. Together with the citation burst of references, the timeline view of the cluster analysis suggested that the basic studies on Ligasure versus Ultracision in thyroidectomy, efficacy and cost‐effectiveness of the UltraCision harmonic scalpel in thyroid surgery, safety and efficacy of new integrated bipolar and ultrasonic scissors is a upsurge of research with great significance.

Conclusions: The institutes and universities from Italy, the United States and China contributed the most documents, showing their prominent influence in this region. The urgent need exists to strengthen academic collaborations among the researchers with functional study of parathyroid protection and postoperative complications.

POSTER 224

Surgery Clinical Poster

TRANSCON PTH ENABLES INDEPENDENCE FROM CONVENTIONAL THERAPY WHILE MAINTAINING NORMAL SERUM CALCIUM IN ADULTS WITH CHRONIC POSTSURGICAL HYPOPARATHYROIDISM: RESULTS FROM A SUB‐ANALYSIS OF THE PATHWAY PHASE 3 TRIAL

Mark Schneider*¹, Bart Clarke², Aliya Khan³, Mishaela Rubin⁴, Peter Schwarz⁵, Dolores Shoback⁶, Claudia Gagnon^7,8, Andrea Palermo^9,10, Lisa Abbott¹¹, Lynn Kohlmeier¹², Filomena Cetani¹³, Elena Tsourdi¹⁴, Rajesh Jain¹⁵, Xuebei An¹, Alden Smith¹, Bryant Lai¹, Jenny Ukena¹, Christopher Sibley¹, Aimee Shu¹, Lars Rejnmark¹⁶

¹Ascendis Pharma Inc, USA,²Mayo Clinic E18‐A, USA,³McMaster University, Canada,⁴Columbia University, USA,⁵Rigshospitalet, Denmark,⁶UCSF/VA Medical Center, USA,⁷CHU de Québec‐Université Laval Research Centre, Canada,⁸Department of Medicine, Université Laval, Canada,⁹Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Campus Bio‐medico, Italy,¹⁰Unit of Endocrinology and Diabetes, Campus Bio‐medico University, Italy,¹¹Northern Nevada Endocrinology, Reno, NV and University of Nevada, Reno, USA,¹²Endocrinology and Spokane Osteoporosis, USA,¹³University Hospital of Pisa, Endocrine Unit, Italy,¹⁴Uniklinikum Dresden, Medizinische Klinik III, Abteilung Endokrinologie, Germany,¹⁵University of Chicago, USA,¹⁶Aarhus University Hospital, Denmark

Objective: Hypoparathyroidism is a rare endocrine disease caused by inadequate levels of parathyroid hormone (PTH). Anterior neck surgery resulting in iatrogenic resection or damage to the parathyroid glands accounts for ∼75% of cases.1 TransCon PTH is an investigational once‐daily prodrug with sustained release of active PTH designed to provide stable PTH levels within the physiological range for 24 hours/day. This analysis assessed the safety and efficacy of TransCon PTH in adults with postsurgical hypoparathyroidism in the PaTHway trial.

Methods: PaTHway is a phase 3 trial of TransCon PTH with a 26‐week randomized, placebo‐controlled, blinded period and ongoing 156‐week open‐label extension. The multi‐component primary efficacy endpoint was the proportion of participants at week 26 with normal serum calcium (8.3–10.6 mg/dL), independence from conventional therapy (no active vitamin D and ≤600 mg/day calcium), and no increase in prescribed study drug over the prior 4 weeks. Key secondary endpoints included Hypoparathyroidism Patient Experience Scale (HPES) Symptom cognitive and physical domain scores, HPES‐Impact physical functioning and daily life domain scores, and the 36‐Item Short Form Survey (SF‐36) physical functioning subscale score.

Results: Of the 82 participants who received study drug, 70 (52 TransCon PTH, 18 placebo) had hypoparathyroidism of postsurgical etiology. Most were female (60/70, 86%) and White (65/70, 93%); the mean age was 51 years. At week 26, 81% (42/52) of postsurgical participants treated with TransCon PTH vs. 6% (1/18) placebo met the primary efficacy endpoint (P < 0.0001). The mean change from baseline to week 26 in all key secondary endpoints improved significantly with TransCon PTH compared to placebo (all P < 0.01). Most treatment‐emergent adverse events were mild or moderate in severity.

Conclusion: Treatment with TransCon PTH was generally well‐tolerated and enabled independence from conventional therapy while maintaining normocalcemia in the subpopulation of PaTHway participants with postsurgical hypoparathyroidism. TransCon PTH improved disease‐related symptoms and the impact of hypoparathyroidism on daily life and physical functioning as well as health‐related quality of life. These results are consistent with the overall findings of the PaTHway trial (N = 82) and suggest TransCon PTH may improve outcomes compared to conventional therapy.

POSTER 225

Surgery Clinical Poster

COMPARISON OF TRANSORAL ENDOSCOPIC THYROIDECTOMY VERSUS CONVENTIONAL OPEN THYROIDECTOMY: A PROSPECTIVE STUDY OF SURGICAL OUTCOME AND QUALITY OF LIFE FROM NORTH INDIA

Prathyusha Godi*, Gyan Chand, Sabaretnam M, Anjali Mishra, Gaurav Agarwal

SGPGIMS, India

Background: Several remote access approaches for the endoscopic thyroid surgery is being practice in the different part of the world. The Transoral Endoscopic thyroidectomy through vestibular approach (TOETVA) demonstrated a new technique of total scar free mid line approach for both lobe of thyroid with minimal dissection and optimum cosmesis.

Objective: The objective of this study is to assess the surgical outcome, cosmetic satisfaction and quality of life after TOETVA in comparison to conventional open thyroid surgery.

Method: This is a prospective non‐randomized study of 61 patients operated by single surgeon at tertiary care referral center in north India. We have selected the small benign thyroid nodule for this study from July 2021 to Nov 2022. 31 patients were enrolled in TOETVA group and 30 patients in COT group during this duration. All patients were evaluated before surgery and two weeks and six months after surgery for their quality of life using Thy‐pro questionnaire and other post‐surgical outcomes with specific questionnaire.

Results: Total 61 patients were evaluated during this study period. The patients in the TOETVA groups are significantly younger than patients in the open surgery group [1.87 years younger(25.8%)]. The mean tumor size overall 2.94cm (TOETVA 2.62cm & Open 3.25cm) and majority were benign STN in both the group, The mean operating time was 30% longer in the TOETVA group (150 mins) than that in the conventional open surgery group (105mins) with p < 0.05. Cost was significantly higher p < 0.05 in TOETVA group. Hospital Stay was lower in TOETVA group, Cosmetic and overall satisfaction were significantly greater in the TOETVA group p < 0.05. The Thyo‐Pro QOL scores of the patients in TOETVA group were generally better than open surgery group.

Conclusions: The TOETVA is safe approach for thyroid surgery with lower hospital stay and better postoperative Quality of life, cosmetic perception and over all satisfaction than the conventional open thyroid surgery. However, the TOETVA approach is costlier.

POSTER 226

Surgery Clinical Poster

REVISITING LORÉ'S RETROGRADE THYROIDECTOMY FROM THE PERSPECTIVE OF PRESERVING THE EXTERNAL BRANCH OF THE SUPERIOR LARYNGEAL NERVE

Gene Huh*¹, Wonjae Cha², Woo‐Jin Jeong², Jung Park³

¹Department of Otorhinolaryngology‐Head & neck Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Korea, Republic of,²Department of Otorhinolaryngology‐Head & Neck Surgery, Seoul National University Bundang Hospital, Korea, Republic of,³Department of Radiology, Seoul Metropolitan Government‐Seoul National University Boramae Medical Center, Korea, Republic of

Objective: Injury to the external branches of the superior laryngeal nerve (EBSLN) is the main reported cause of inexplicable post‐thyroidectomy dysphonia without recurrent laryngeal nerve (RLN) injury. The objective of this study is to evaluate EBSLN function following Loré's retrograde thyroidectomy (RT) and compare it to conventional thyroidectomy (CT) using postoperative electromyography (EMG).

Methods: This retrospective study was conducted at a single tertiary center. Consecutive patients who had undergone CT or RT were included. Bilateral EMG of the cricothyroid muscle was performed 2–3 months postoperatively in all patients. Patient characteristics, postoperative findings of bleeding events, drain amount, hypocalcemia, calcium replacement, RLN function, and EBSLN function were thoroughly reviewed and compared between the two surgical approaches. Abnormalities in the EMG findings were reported based on the wave configuration, and the results were graded into four categories.

Results: 731 consecutive patients who underwent CT (n = 341), or RT (n = 391) were included, and a total of 1179 RLNs and EBSLNs were at risk in CT (n = 601) and RT (n = 578). The CT and RT groups had similar clinical characteristics and surgical data. Two groups presented similar postoperative results for bleeding incidence, drain amount, and hypocalcemia. All RLNs were identified in both groups and their permanent function was preserved. EBSLN was significantly less frequently identified in the surgical field during RT than it was during CT (0.3% vs. 4.2%, respectively; P < 0.001). Abnormal rates of postoperative EMG on the EBSLN were significantly lower in the RT group than in the CT group (1.7% vs. 7.8%, respectively; P < 0.001), while the CT group presented with a higher grade of abnormal EMG (P < 0.001).

Conclusions: The RT technique may be beneficial for preserving EBSLN function. Meticulous capsular dissection and appropriate traction of the upper pole facilitated by RT are crucial for decreasing the risk of EBSLN injury, which can be achieved without directly identifying the nerve.

POSTER 227

Surgery Clinical Poster

RECURRENT THYROIDECTOMY: A NOVEL APPROACH TO IDEAL THERAPY

Abdulwahid Salih*¹, Yadgar Saeed¹, Fahmi Kakamad²

¹Smart Health Tower, Iraq,²Smart Health Tower, Iraq

Abstract

Introduction: The most challenging aspect of thyroid surgery is the reoperation because of the high risk of complications. This study aims to demonstrate that a modified thyroidectomy method efficiently minimizes associated complications in subsequent thyroidectomies to nearly zero.

Method: This single‐group cohort study included patients who had undergone a recurrent thyroidectomy. Associated laboratory tests have been conducted. The patients vocal cord function was assessed. High‐volume surgeons performed the surgeries utilizing a modified thyroidectomy approach, which involves the following steps: 1) Identify and preserve parathyroid glands before looking for the recurrent laryngeal nerve (RLN); 2) look for the RLN to appear in any area of the neck until it is identified; 3) begin the dissection at the suprasternal notch to locate the RLN in the tracheoesophageal groove; 4) if the nerve was not discovered in the suprasternal notch, the exploration would proceed to the nerve's predicted entry to the cricoid cartilage.

Result: This study included 195 patients who underwent recurrent thyroidectomies. Female patients (173, 88.7%) dominated male patients (22, 11.3%). In 138 cases (70.7%), the most frequent ultrasonographic finding was multinodular goiter. The majority of patients (160, 82%) had total thyroidectomy, whereas 35 (18%) had thyroid lobectomy. Both RLNs were explored in all cases undergoing total thyroidectomy, and the concerned lateral RLN was seen after thyroid lobectomies. There was not any damage done to the RLNs, and only 15% of the individuals experienced transient hypocalcemia.

Conclusion: When performed by high‐volume surgeons using a modified approach, recurrent thyroidectomies are achievable without significant complications.

POSTER 228

Thyroid Cancer Basic Poster

THYROID HORMONE RECEPTOR Α1: A NOVEL REGULATOR OF THYROID CANCER CELL DIFFERENTIATION

Eunmi Hwang*, Woo Kyung Lee, Yuelin Jack, Xuguang Zhu, Li Zhao, Yanlin Yu, Sheue‐yann Cheng

Center for Cancer Research, National Cancer Institute, NIH, USA

Objective: Thyroid hormone receptor α1 (TRα1) functions as a transcription factor to initiate and drive cellular programs to promote differentiation in various cell types in normal physiological conditions. However, it is largely unknown how TRα1 can act as a transcription factor to regulate the differentiation of human cancers. Here we aim to understand the role TRα1 in the differentiation of cancer cells using anaplastic thyroid cancer cells (ATC) as a model.

Methods: We used two human ATC cell lines, THJ‐11T (11T) and THJ‐16T (16T), for our studies. The expression of the THRA gene in ATC cells is silenced. We stably expressed TRα1 in three clones each in 11T (11T‐TRα1 #2, #7, and #8) and 16T (16T‐TRα1 #3, #4, and #8) cells. We used various molecular approaches to analyze effects of TRα1 on proliferation and apoptosis of ATC cells in vitro and in vivo using xenograft models. We used single cell transcriptomic analysis (scRNA‐seq) of tumors induced by 16T‐ and 16T‐TRα1 to elucidate how TRα1 can suppress tumor growth and re‐differentiate highly de‐differentiated ATC cells.

Results: Analysis of the human thyroid cancer database of The Cancer Genome Atlas (TCGA) showed that THRA gene expression is lost in ATC. The expressed TRα1 inhibited ATC cell proliferation and induced apoptosis in vitro in cell models and in vivo in xenograft models. Analysis of differentiation scores showed that THRA gene expression was most positively correlated with the paired box gene 8 (PAX8) gene. We found that the expressed TRα1 increased the PAX8 gene expression in ATC cells at the mRNA and protein levels. Using ChIP and reporter assays, we showed that TRα1 bound to a thyroid hormone response element on the upstream promoter of the PAX8 gene to directly activate the expression of the PAX8 gene. Analysis of scRNA‐seq data demonstrated that TRα1‐induced PAX8, via its transcription programs, shifted the cell landscape of ATC toward a more differentiated state.

Conclusions: Our studies indicate that TRα1 is a newly identified regulator of thyroid cancer cell differentiation and could be considered as a potential therapeutic target to re‐differentiate ATC to improve the outcome of ATC patients.

POSTER 229

Thyroid Cancer Basic Poster

ASSESSMENT OF ONCOGENIC MUTATIONS/FUSIONS IN PAPILLARY THYROID CANCERS FROM ADULTS EXPOSED TO RADIATION AFTER THE CHERNOBYL ACCIDENT

Kirk Jensen*¹, Aneeta Patel¹, Dorina Ylli², Maksym Gorobeiko³, Viktoria Hoperia³, Vasyl Vasko¹

¹Uniformed Services University of the Health Sciences, USA,²Mother Teresa Hospital, Albania,³Taras Shevchenko National University of Kyiv, Ukraine

Background: Eighty‐six percent of U.S. military personnel are less than 40 years old and at an increased risk of exposure to ionizing radiation. Radiation is a well‐established risk factor for development of papillary thyroid cancer (PTC).

Objective: To examine pathological and molecular characteristics in PTCs from adult residents of Ukraine with history of exposure to radiation after the Chernobyl accident (1986).

Material and Methods: PTCs from 34 Ukrainian patients, 25 years old or more in 1986, were examined. Nucleic acids were extracted from paraffin‐embedded samples, and digital PCRs with multiplex probes for mutant and wild‐type of BRAF, RAS, TERT, RET/PTC1, RET/PTC3 and ETV6/NTRK3 were performed using a QuantStudio dPCR platform.

Results: Ages at time of exposure and time of surgery were 30.6 ± 3.5 and 46.4 ± 5.2 years respectively. There were 17 male and 17 female patients, with 32 classical PTCs and 2 follicular variant PTCs. The average tumor size was 2.0 ± 1.0 cm. Multifocal growth, lymph node metastases and extra‐thyroidal invasion were detected in 12/34 (35.2%), 22/34 (64.7%) and 19/34 (55.8%) cases. Genomic alterations were detected in 29/34 (85.2%) cases. BRAF mutations were found in 14/34 (41.1%). Analysis of gene translocations revealed RET/PTC1 in 5/34 (14.7%) and RET/PTC3 in 10/34 (29.4%) cases. There were no PTCs harboring RAS, TERT or ETV6/NTRK3. The latency periods for tumors harboring BRAF mutations and RET/PTC fusions were 16.8 and 15.3 years, respectively, (p = 0.05). In two cases, BRAF mutation and RET/PTC fusions were detected simultaneously, demonstrating aggressive morphological features and being characterized by shorter latency (13 years).

Discussion and Conclusions:

The patients examined in our study could serve as a model representative of a significant proportion of the U.S. military. Tumors from individuals with history of exposure to radiation in adulthood have pronounced invasive features. A significant proportion of these tumors harbor gene fusions suggesting a possible association between irradiation in adulthood and development of radiation‐inducible PTCs.

POSTER 230

Thyroid Cancer Basic Poster

SCREENING TUMOR STAGE SPECIFIC CANDIDATE NEOANTIGENS OF THYROID ADENOCARCINOMA INTEGRATING THE EXOME SEQUENCING AND TRANSCRIPTOME SEQUENCING

Meng Jia*¹, Jiawen Liang¹, Zhuyao Li¹, Ye Qin¹, Qianqian Li¹, Jianwei Wang², Xiubo Lu¹

¹The First Affiliated Hospital of Zhengzhou University, China,²Zhengzhou University, China

Objective: As the most common endocrine tumor, the incidence of thyroid carcinoma (THCA) continues to increase worldwide. Although the overall prognosis for THCA is good, patients with distant metastases have a mortality rate of 5‐20%. In recent years, more and more immunotherapy has been applied in various malignant tumors, making it widely accepted as antigens encoded by tumor‐specific mutated genes. The aim of our study is to improve the diagnosis and overall prognosis of thyroid cancer patients.

Methods: We screened specific candidate neoantigen genes in early and late THCA by combining transcriptome and somatic cell mutations. Top five early stage neoantigen related genes (NRGs) were identified, namely GPR4, CSPG4, TENM1, PROS1, TK1, and top five late stage NRGs were identified, namely CDH6, SEMA6B, DYSF, XPR1 and ABR. Then, we used machine learning models to verify the ability to screen NRGs, and analyzed the correlation between NRGs with immune cell types and immune checkpoint regulators.

Results: The results showed that the candidate antigen genes could not only construct a better diagnostic model (AUC value of early group was higher than 0.979, late stage was higher than 0.959). The prognostic model was constructed to predict the NRGs survival curve, and the 1‐year, 3‐year and 5‐year AUC values were 0.83, 0.87 and 0.86 respectively, also were closely related to different immune cell types. By comparing the expression trend and mutation frequency of NRGs in multiple tumors, we found that NRGs have the potential to develop broad‐spectrum therapeutic drugs.

Conclusion: Our candidate NRGs have the potential to be used as therapeutic targets and diagnostic biomarkers that can develop broad‐spectrum therapeutic agents.

POSTER 231

Thyroid Cancer Basic Poster

ANALYSIS OF INFILTRATED TUMOR MICROENVIRONMENT IN PAPILLARY THYROID CARCINOMA WITH HASHIMOTO THYROIDITIS

Yaosheng Luo^1,2, Jie Yao³, Jie Shen*³

¹The Second Affiliated Hospital of Guangzhou Medical University, China,²Shunde Hospital, Southern Medical University, China,³Shunde Hospital of Southern Medical University, China

Background and Objective Hashimoto thyroiditis (HT) has binary effects of papillary thyroid carcinoma (PTC). Previous studies indicated that the increase of infiltrated lymphocytes in HTPTC is associated with improved prognosis. However, the knowledge of HTPTC tumor microenvironment and the characteristics of cell interaction are not clear at present. Therefore, this study intended to elucidate the characteristics of the HTPTC tumor microenvironment via single cell RNA sequencing and other necessary experiments.

Methods We retrospectively collected the clinical data of 679 patients with PTC who underwent surgery. Kaplan‐Meier and COX regression were used to analyze whether there was a correlation between prognosis and HT, as well as in TCGA cohort. Then, we further analyzed the characteristics of thyrocytes and T cells by scRNA‐seq, and verified the changes of these characteristics via immunohistochemistry/fluorescence (IHC/IF), RNA in situ hybridization (RNA‐ISH), and in vitro experiments. We further explored the origin of CD8+T cells through trajectory analysis and IHC/IF. Cell‐Cell Communication analysis was used to investigate the possible mechanism that may promote the activation and tumor infiltration of CD8+T cells.

Results HTPTC was associated with prolonged disease‐free survival (DFS) (P < 0.05); similar results were found in TCGA cohort. There was significantly more CD8+T infiltration within HTPTC tumors (P < 0.0001). Compared to PTC, HTPTC tumor epithelial cells showed active antigen presentation, activation of IFN‐γ downstream pathway STAT1 and upregulation of PD‐L1 expression; CD8⁺GZMK⁺T cells infiltrated in HTPTC increasingly. Stimulated by IFN‐γ, in vitro experiments confirmed that the proliferation and migration of PTC cell lines were inhibited, while pSTAT1 and PD‐L1 proteins were upregulated, which was consistent with the characteristics of infiltrating immune microenvironment. CD8⁺GZMK⁺T cell may be derived from tertiary lymphoid structure (TLS) in HTPTC adjacent tissue.

Conclusion HTPTC has a better prognosis than non‐HTPTC, which is related to the anti‐tumor microenvironment formed by combined HT.

POSTER 232

Thyroid Cancer Basic Poster

ACTIVATION OF THE PROMOTER REGION OF EZH2 HISTONE METHYLTRANSFERASE IN ANAPLASTIC THYROID CANCER

Marcella Cristovão, Diego de Mello, Edna Kimura, Cesar Fuziwara*

University of São Paulo, Institute of Biomedical Sciences, Brazil

Objective: Anaplastic Thyroid Carcinoma (ATC) is the most aggressive type of thyroid cancer and overexpresses EZH2, the catalytic subunit of the Polycomb 2 complex, that promotes gene silencing by trimethylation of histone H3 at the lysine 27 (H3K27Me3). Thus, EZH2 activation may result in ATC cell dedifferentiation and influence tumor progression. Hence, we aim to investigate the mechanism of transcriptional activation of EZH2 in ATC.

Methods: We cloned fragments of the EZH2 promoter region spanning the upstream region of exon 1, named as E1, E2, E3, E4 and E5. Later, E3 and E4 were divided into smaller ones: E3A, E3B and E3/4 (intersection of E3 and E4). These fragments were cloned in pGL4‐20 minP luciferase plasmid and tested in ATC cells ‐ KTC2, SW1736, 8305C ‐ and papillary thyroid carcinoma cells ‐ TPC‐1 and BCPAP. Transcription factor (TF) prediction was performed on LASAGNA software and TFs with higher scores were analyzed by qPCR. Moreover, site directed deletion of TFs motifs was performed in E3/4 plasmid. We also treated ATC cells with a MAPK inhibitor (U0126) to assess the impact on EZH2 activation.

Results: E3 and E4 regions showed the highest luminescence values, while the intersection region, E3/4, retained high luciferase activation. Based on TF prediction analysis, we selected YY1, E2F1, NKX2.5, NFYA, FOXM1 and SP1 for qPCR analysis and found most of these TFs were upregulated in ATC. Deletion of NFYA and YY1 motifs within E3/4 region resulted in a decrease in EZH2 promoter activation, and when both sites were deleted, the effect observed was additive. Deletion of SP1 motif reduced E3/4 activation indicating a link between MAPK signaling and EZH2 transcription. Indeed, MAPK inhibition reduced EZH2 expression and promoter activation in ATC cells.

Conclusion: the E3/4 fragment is the minimum promoter of EZH2 and presents motifs for TFs that are overexpressed in ATC. Deletions in NFYA, YY1 and SP1 motifs in E3/4 reduced promoter activation levels, indicating a correlation between those TFs and EZH2 transcriptional activation. Moreover, MAPK blockage reduces EZH2 promoter activation and expression, indicating that EZH2 activation in ATC is dependent on MAPK signaling.

POSTER 233

Thyroid Cancer Basic Poster

MANNOSE POTENTIATES THE ANTITUMOR EFFECTS OF BRAF KINASE INHIBITORS BY SUPPRESSING GLYCOLYSIS AND ACTIVATING CYTOTOXIC T CELLS

Sharui Ma*¹, Yuxin Ma², Liumei Song²

¹Shaanxi Provincial People's Hospital, China,²Xi'an Jiaotong University, China

Objective: Our previous research has demonstrated that the natural hexose, mannose, preferentially inhibits the progression of thyroid cancer with low expression of the zinc ion transporter ZIP10. Although BRAF kinase inhibitors have been approved for the treatment of BRAF‐mutated thyroid cancer, their clinical benefits are often limited. This study aims to investigate the mechanism by which mannose enhances the antitumor effects of BRAF kinase inhibitors.

Methods: We employed MTT assays, colony formation assays, flow cytometry, and subcutaneous xenograft mouse models to determine whether mannose enhances the antitumor effects of BRAF kinase inhibitors. The underlying mechanism of mannose sensitizing the antitumor effect of BRAF inhibitors was elucidated through a series of molecular and biochemical experiments in vitro and in vivo.

Results: Our findings revealed that mannose and BRAF kinase inhibitors synergistically killed BRAF‐mutated thyroid cancer cells in vitro and in vivo. Mechanistically, we demonstrated that BRAF kinase inhibitors increased the sensitivity of thyroid cancer cells to mannose by decreasing the expression of ZIP10. Concurrently, mannose reversed resistance to BRAF kinase inhibitors by inhibiting glycolysis and consequently reducing ATP levels, which provide phosphate groups for AKT and ERK. Remarkably, T cell‐mediated tumor cell‐killing assays also indicated that mannose activated cytotoxic T cells and enhanced their in vitro killing abilities. Moreover, the combination of mannose and BRAF kinase inhibitors further improved the antitumor effects of T cells. Lastly, we established a BRAFV600E transgenic mouse model of primary papillary thyroid cancer to demonstrate that mannose sensitized the antitumor effect of BRAF kinase inhibitors by activating CD8⁺ T cells.

Conclusion: Collectively, through a series of in vivo and in vitro experiments, this study elucidates that mannose enhances the antitumor effects of BRAF kinase inhibitors by suppressing glycolysis and the phosphorylation of AKT and ERK while concurrently activating cytotoxic T cells. Based on these findings, this research provides a mechanistic rationale for exploring the clinical use of combined treatment with mannose and BRAF kinase inhibitors in thyroid cancer.

POSTER 234

Thyroid Cancer Basic Poster

FIBROBLAST DERIVED EXTRACELLULAR MATRIX DRIVES TUMOR PROMOTING CHANGES IN MACROPHAGES WITHIN THE THYROID TUMOR MICROENVIRONMENT

Nikaela Bryan*, Grace Purvis, Aime Franco

Children's Hospital of Philadelphia, USA

Thyroid cancer is the most common endocrine malignancy, and it is projected to become the fourth most diagnosed cancer in the US by 2030. Papillary thyroid carcinomas (PTCs) is the most common form of thyroid cancer making up 80% of all well‐differentiated thyroid carcinomas, and accounts for almost all of the increase in thyroid cancer incidence over the last several decades. The most common gene alteration in thyroid cancer, especially in PTCs, is BRAFV600E. Our lab has previously shown that murine BrafV600E‐driven papillary thyroid carcinomas (PTCs) are enriched with cancer associated fibroblasts (CAFs) that secrete a collagen‐rich extracellular matrix (ECM). PTCs are also enriched with tumor associated macrophages (TAMs). Additionally, collagen enhances Braf‐driven thyroid tumor cell motility in vitro. This led us to hypothesize that CAFs and the collagen rich ECM could drive progression of PTCs through enabling TAMs to promote tumorigenesis. To test this hypothesis, we optimized a protocol to allow CAFs to deposit a collagen‐rich ECM, and then decellularizing the matrix to leave behind only the ECM. The enrichment of collagen, and absence of cells in the ECM was confirmed via immunofluorescence and Western Blot analysis for collage. We plated macrophages on CAF ECM to determine its effect on macrophage adherence and polarization. ECM had no effect on the macrophage adherence, but it does upregulate macrophage expression of TNF‐α and IL‐10. Increased secretion of these cytokines stimulated by ECM was confirmed by ELISA. Further, these secreted cytokines enhanced a macrophage polarization feedback loop. These data suggest CAF secreted ECM can polarize macrophages in the TME to a pro‐tumorigenic state

POSTER 235

Thyroid Cancer Translational Poster

VALIDATION AND ASSESSMENT FEASIBILITY OF HSA‐MIR‐139‐5P EXPRESSION AS A PROGNOSTIC MARKER IN THYROID CANCER

Natalia Martínez‐Puente*^1,2, Ignacio Ruz‐Caracuel³, Luis Leandro‐García¹, Héctor Pian‐Arias³, Sandra Campos‐Mena³, Amparo Benito‐Berlinches³, Irene González‐García³, Laura García‐Tobar⁴, María Lozano‐Escario⁴, Sonsoles Guadalix⁵, Rocío Letón¹, Roberta Radu¹, Ángel Martínez‐Montes¹, María Monteagudo¹, Sara Mellid¹, Alberto Díaz‐Talavera^1,2, Ester Arroba¹, Carlos Valdivia¹, Javier de Nicolás‐Hernández¹, Alicia Arenas¹, Alberto Cascón^1,2, Cristina Rodríguez‐Antona^1,2, Eduardo Caleiras¹, Juan Galofré⁴, María Currás‐Freixes¹, Pablo Valderrábano^3,6, Mercedes Robledo^1,2, Cristina Montero‐Conde^1,2

¹CNIO, Spain,²CIBERER, Spain,³Hospital Universitario Ramón y Cajal, Spain,⁴Clínica Universidad de Navarra, Spain,⁵Clínica Universidad de Navarra, Spain,⁶Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Spain

Introduction: Patients with recurrent/persistent differentiated thyroid carcinoma are often radioiodine refractory and present worse outcome with increased mortality [1]. Early detection of these patients is critical for the appropriate disease management and follow‐up [2]. In this regard, previous work from our group [3] involving miRNome sequencing found hsa‐miR‐139‐5p (miR139) down‐expression associated with recurrent/persistent disease independently of tumor genetic background.

Objectives: To validate the prognostic value of miR139‐expression in an independent series of paired thyroid tumor/normal samples enriched with poor prognosis cases and estimate a threshold to dichotomize the cases. To determine the feasibility of incorporating miR139‐testing into the clinical setting using an in situ hybridization technique.

Methods: RNA from formalin‐fixed paraffin‐embedded tissue sections of normal thyroid tissue, thyroid tumors and metastases, when available, from 57 patients was extracted using the truXTRAC^® FFPE total NA Kit. MiR139 expression was then measured by qPCR using the miRCURY^® LNA^® miRNA SYBR^® Green PCR kit. The expression of four housekeeping miRNAs was also analyzed and the geometric mean of these four values was used as the normalizer for the analysis of miR139‐expression data. Two‐tailed Mann‐Whitney test was performed to analyze the association between clinicopathological and molecular variables. P‐values ≤0.05 were considered statistically significant. RNA in situ probe hybridization of pre‐miR139 was used to test miR139‐expression in whole sections of surgical specimens.

Results: Paired tumor/normal data analysis confirmed a significant miR139‐expression reduction in tumors (55% tumor/normal median down‐expression). This reduction was more significant in patients with persistent/recurrent disease (68%) compared to patients with excellent response (49%). The reduction of miR139‐expression in metastases from patients with persistent/recurrent disease was similar to that observed in primary tumors from the same patient group. In addition, AUC‐ROC curve comparative analysis of miR139‐expression versus TERT promoter mutation prognostic marker showed that miR139 had a higher power to discriminate prognostic groups in our series. Preliminary miR139 in situ quantification results will be also presented.

Conclusion: Our results confirm the value of miR139‐expression as a prognostic marker in thyroid cancer and underscores the clinical utility of in situ miR139‐expression assessment in diagnostic biopsies.

POSTER 236

Thyroid Cancer Translational Poster

OPTIMIZING FACE VALIDITY AND CLINICAL RELEVANCE OF A THYROID CANCER MICROSIMULATION MODEL USING A NOVEL STAKEHOLDER ADVISORY GROUP

Louise Davies*^1,2,3, Sara Fernandes‐Taylor⁴, Natalia Arroyo⁴, Yichi Zhang⁴, Erin Bowles⁵, Oguzhan Alagoz⁴, David Francis⁴

¹The VA Outcomes Group, Department of Veterans Affairs Medical Center, USA,²Geisel School of Medicine at Dartmouth, USA,³The Dartmouth Institute for Health Policy and Clinical Practice, USA,⁴University of Wisconsin‐Madison, USA,⁵Kaiser Permanente Washington, USA

Objective: We developed the PApillary Thyroid CArcinoma Microsimulation model (PATCAM; NIH R01 2020‐2025), a mathematical model which replicates thyroid cancer epidemiology in the U.S. over time. Models like PATCAM can answer research and policy questions in cases where developing prospective evidence is not feasible – an example is breast cancer modeling to make USPSTF recommendations on breast cancer screening. A model's utility can be limited if it lacks face validity or is not directly clinically relevant, we proposed a solution: incorporate formal stakeholder input. This study describes the methods used to establish the stakeholder group and the impact it has had thus far on model development.

Methods: Participatory action research approach incorporating focus group techniques, bidirectional learning and coproduction principles. The aim is for PATCAM to have clinical relevance and face validity so that output that can be applied to questions important to providers, policy makers, and patients to support changes in guidelines and policy.

Results: The stakeholder advisory group was designed to capture key perspectives and knowledge areas the group comprises representation from endocrinology, epidemiology, primary care, payors/healthcare delivery, radiation oncology, radiology, surgery, and thyroid cancer survivors. Their input informed development of a conceptual model of thyroid cancer detection and provided insight requested from the modeling team on (1) the role of size in biopsy decisions, (2) trends in provider biopsy behavior, and (3) specialty propensity to biopsy. Last, the advisory group provided the qualitative data on current clinical beliefs and practices used to develop crucial model assumptions in the following areas: underlying prevalence of thyroid cancer in the population over time, the proportion of malignant tumors showing regression, and differences in cancer prevalence by sex and age.

Conclusion: An advisory group provided real world expertise and insight to support assumptions required to build the PATCAM microsimulation model but for which there is a lack of strong evidence. The advisory group input increased face validity, making it more likely the model will be a successful resource to guide future thyroid cancer guideline and policy development.

POSTER 237

Thyroid Cancer Translational Poster

ENVIRONMENTAL EXPOSURES AND PEDIATRIC THYROID CANCER: AIR POLLUTION AND ARTIFICIAL LIGHT AT NIGHT

Nicole Deziel*¹, Rong Wang¹, Joshua Warren¹, Catherine Dinauer², Jennifer Ogilvie², Joseph Wiemels³, Libby Morimoto⁴, Catherine Metayer⁴, Xiaomei Ma¹

¹Yale School of Public Health, USA,²Yale School of Medicine, USA,³University of Sothern California, USA,⁴University of California, USA

Background: Pediatric thyroid cancer has been increasing the United States and globally. The etiology is largely unknown, although environmental exposures have been hypothesized to contribute to the rising incidence. Objective: We evaluated the relationship between pediatric papillary thyroid cancer (ages 0‐19 years) and perinatal exposure to two environmental carcinogens with evidence of thyroid function disruption: artificial light at night and ambient fine particulate matter (PM2.5). Methods: Using linked birth records and cancer registry data from California, we conducted a nested case‐control study of papillary thyroid cancer patients diagnosed at 0‐19 years and born in 1982‐2011 (n = 736 cases, 36,800 controls). We used the New World Atlas of Artificial Night Sky Brightness, a computational technique for mapping light pollution using a remote sensing database, to assign individual‐level light pollution exposure based on maternal address at birth. We obtained daily PM2.5 at 1‐km2 grids from a validated, ensemble‐based prediction model and assigned exposure as the average PM2.5 concentration at the birth residence during an individual's birth month. We calculated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression, adjusting for potential confounders and conducted analyses stratified by age and race/ethnicity. Results: For light at night, we observed an increased odds of papillary thyroid cancer in higher exposure categories compared to the reference group (2nd tertile: OR: 1.25, 95%CI 1.04‐1.50; 3rd tertile: OR: 1.23, 95%CI: 1.02‐1.50). OR appeared more pronounced among those who were 15‐19 years at diagnosis compared to younger cases (2nd tertile: 1.40 95%CI: 1.12‐1.75; 3rd tertile: 1.28, 95%CI 1.01‐1.62). We also observed associations between log(PM2.5) exposure and thyroid cancer risk (OR: 1.17, 95%CI: 1.01‐1.36); OR were of greater magnitude among Hispanic children (OR: 1.33, 95%CI: 1.06‐1.66) and children ages 15‐19 years (OR: 1.22; 95%CI: 1.02‐1.45). Conclusions: This study provides the first evidence of independent associations between early‐life exposure to both artificial light at night and PM2.5 and pediatric papillary thyroid cancer and suggests that certain subgroups may be at greater risk. This supports an etiological role of environmental exposures and thyroid cancer in children and highlights the need for additional epidemiologic studies in this area.

POSTER 238

Thyroid Cancer Translational Poster

INVESTIGATING THE ONCOGENIC VARIATION OF PEDIATRIC DIFFERENTIATED THYROID CANCER FROM FFPE SAMPLES USING RNA SEQUENCING AND WHOLE EXOME SEQUENCING

Gurpreet Kaur¹, Manavalan Gajapathy¹, Brandon Wilk¹, Donna Brown¹, Leen Matalka¹, Diana Lin¹, Shuko Harada¹, Elizabeth Worthey¹, Pallavi Iyer*²

¹University of Alabama at Birmingham, USA,²Medical College of Wisconsin, USA

Objective: Thyroid cancer is the second most common cancer in US pediatric females. Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the most common types of differentiated thyroid carcinoma (DTC), and are more aggressive in the pediatric population than in adults. In this study, we aim to identify genomic characteristics of DTC using RNA‐Seq and whole exome sequencing (WES).

Methods: The study includes 45 formalin‐fixed paraffin‐embedded (FFPE) surgical samples (tumor‐normal) from pediatric patients with female predominance (<19 years), collected from 2017‐2020. RNA‐Seq and WES were performed targeting 150M PE and 40M SE reads per sample, respectively. After quality control, we employed nf‐core RNA‐Seq and GATK germline and somatic variant pipelines for secondary analysis, limma and DESeq2 R packages for RNA‐Seq downstream analysis. Variant analysis was conducted using cBioPortal and mutational signatures identification using MSISensor2 and SigProfilerExtractor.

Results: The ATM, BRAF, IDH, KMT2C, MAP3K1, MET, MSH2, MTOR, PIK3CA, PTEN, SDHA, and SETD2 variants were identified in PTC cases, while the BRCA1, GNAS, and MSH6 variants in FTC. DICER variants were seen in minimally invasive FTC and follicular adenoma, and HRAS and PMS2 variants in noninvasive follicular thyroid neoplasm with papillary‐like nuclear features. NRAS and RET variants were seen in both PTC and FTC. Mutational signature analysis identified signatures of mutational processes including defective homologous recombination‐based DNA damage repair. Unlike adults, no pathogenic variants were noted in KRAS, TP53, or TERT. Pathogenic variation associated with thyroiditis were also identified in a small percentage of samples including DUOX2, TSHR and TG. PCA analysis from the transcriptomes revealed distinctive clusters for tumor and normal samples. Moreover, upregulation of key oncogenic genes, such as H/K/NRAS, ALK and CTNNB1 and downregulaton of thyroid‐specific genes, such as TSHR, DICER1, PTEN, CDKN2A and PAX8 was observed. Data analysis on fusion and SV findings and pathway analysis is ongoing.

Discussion/ Conclusion: To the best of our knowledge, this is the first study that describes a cohort of pediatric thyroid cancer patients in the US Southeast region. These findings expand our understanding of the molecular mechanisms underlying tumor development, progression and response to treatment, and may ultimately assist in the development of individualized treatment plans for this rare patient population.

POSTER 239

Thyroid Cancer Case Study Poster

A CASE REPOT OF RECURRENT NON‐RADIOIODIONE‐AVID MALIGNANT STRUMA OVARII

Nikola Besic*, Rok Petric, Gasper Pilko

Institute of Oncology, Slovenia

Introduction: Malignant struma ovarii (MSO) is a rare thyroid cancer arising within an ovarian teratoma. The treatment is not standardized and there are scarce data on treatment of recurrent non‐radioiodione‐avid MSO.

Description of the Case: A 53‐year‐old female had a unilateral laparoscopic salpingo‐oophorectomy due to the cystic tumor of the left ovary (11 x 9.5 x 3 cm) in 2016. The tumor ruptured and the serous discharge was aspirated and abdominal cavity washed. Tumor was removed through a mini‐laparotomy. Histology revealed MSO (follicular variant of papillary thyroid carcinoma (PTC), mostly encapsulated, without vascular invasion, necrosis, atypia or higher proliferative activity). A total thyroidectomy and ablation of thyroid remnant with 101 mCi of radioactive iodine‐131 (RAI) using rh‐TSH was done. On L‐thyroxine suppressive therapy thyroglobulin (Tg) concentration was between 1.37 and 12.2 mcg/L (Tg‐antibodies negative) till 2020. In 2021, the patient was asymptomatic, but Tg increased to 308 mcg/L. There were no pathological accumulation on ¹⁸F‐FDG‐PET/CT or whole‐body RAI scintigraphy. MRI investigation revealed a pathologically changed right ovary. A hysterectomy with right salpingo‐oophorectomy, partial omentectomy and marginal resection of the 7^th segment of the liver was done. Histology showed only an infiltrate of PTC next to the uterus with a diameter of 3.5 cm. Tg levels dropped to 50 mcg/L, but after one year rose to 194 mcg/L. ¹⁸F‐PET/CT investigation raised the suspicion of the progression of metastasis in the mesentery and of a new small peritoneal deposit. MRI examination showed signs of peritoneal dissemination. An omentectomy, removal of deposits from the mesentery of the small intestine, mesocolon of the sigmoid intestine and stomach was done. Histology revealed two metastases of PTC (13 mm and 5 mm) in the mesentery of the small intestine and a metastasis of PTC (8 mm) of the sigmoid intestine – all had clear surgical margins. Tg was 40 mcg/L after two months, which means that the patient is probably not completely cured.

Discussion: Spillage of MSO may cause tumor recurrence in abdominal cavity. After total thyroidectomy and RAI ablation, Tg is a reliable tumor marker of recurrence of MSO. Diagnosing peritoneal recurrence of non‐radioiodione‐avid MSO is challenging. Surgical resection is a treatment option for recurrent non‐radioiodione‐avid MSO.

POSTER 240

Thyroid Cancer Case Study Poster

GLP‐1 RECEPTOR AGONIST USE IN THE PRESENCE OF A THYROID MASS: A CASE STUDY IN NAVIGATING COMPLEXITIES

Justin Dower*^1,2, Mario Ochoa‐Prieto²

¹Yale New Haven Hospital, USA,²Fair Haven Community Health Center, USA

Introduction: Dulaglutide, like other drugs with GLP‐1 receptor agonist (GLP‐1 RA) activity, carries a risk of inducing C‐cell tumors of the thyroid on its FDA label. Animal studies have demonstrated that GLP‐1 RAs cause growth of such tumors in mice and rats,¹ likely due to expression of GLP‐1 receptors in thyroid C cells. Humans do not express GLP‐1 receptors in healthy C cells; they do express GLP‐1 receptors in medullary thyroid cancer (MTC), but to a much lesser extent than in mice or rats with the same.² Personal or family history of MTC or MEN2 syndrome remains a contraindication to use of GLP‐1 RAs. Presented here is a case that demonstrates management of dulaglutide use in a patient with a new thyroid mass, developed after initiation of the drug.

Description of the Case: A 71‐year‐old man presented to clinic with neck swelling, hoarseness, and dysphagia that developed 2‐3 months after initiation of dulaglutide for Type 2 Diabetes Mellitus. He had no personal or family history of thyroid cancer or other components of multiple endocrine neoplasia and no known exposure to radiation. Out of concern for GLP‐1‐RA‐associated MTC, dulaglutide was discontinued in favor of insulin glargine. Ultrasound revealed a solid, heterogeneous, and hyperemic mass in the right lobe of the thyroid. FNA revealed a follicular neoplasm with mutations conferring a high probability of malignancy. Patient underwent total thyroidectomy, revealing a high‐grade, widely invasive follicular thyroid carcinoma, up to 7.2cm in size. Post‐thyroidectomy radioactive iodine was administered.

Given no pathological evidence of MTC and the patient's previous response to dulaglutide, the decision was made to resume dulaglutide and gradually increase it to the maximum dose.

Discussion: While there is a lack of evidence that GLP‐1 RAs promote MTC in humans, their ability to cause MTC in rats and mice has led to the cautionary avoidance of these drugs in patients with confirmed or suspected MTC. This case highlights the complexities of managing GLP‐1 RAs in patients presenting with a thyroid mass and the exceptional benefits of these drugs by showcasing their safety and efficacy once MTC is ruled out.

POSTER 241

Thyroid Cancer Case Study Poster

A RARE PRESENTATION OF ANAPLASTIC THYROID CARCINOMA: THYROID ABSCESS

Marta Ahmed*, Yisak Debodina, Hannan Yimam

St paul's hospital millanium medical college, Ethiopia

Introduction: Anaplastic thyroid cancers are undifferentiated tumors of the thyroid follicular epithelium. Patients commonly present with rapidly expanding neck mass with invasion of surrounding structures. Most of patients are incurable, nevertheless a multimodality approach improve local control and extend the survival. (1)

Description of the Case: A 60 ‐year‐old woman who presented to the surgical emergency room with shortness of breath and stridor of 2 days duration, accompanied by anterior neck mass for 1 month prior to her presentation. On examination she had firm and tender anterior neck mass with erythematous of the overlying skin. Ultrasound examination of the thyroid was suggestive of right thyroid lobe predominantly cystic lesion with peripheral solid component. Ultrasound guided fine needle aspiration cytology shows features of thyroid inflammation but no features of malignancy seen. With the initial diagnosis of upper airway obstruction secondary to thyroid abscess patient intubated and put on mechanical ventilation. Right thyroid lobectomy with thyroid abscess drainage done , specimen sent for biopsy. After one week patient was discharged home with no complications. Two weeks letter she came to follow up clinic with biopsy result which is diagnostic for anaplastic thyroid carcinoma squamous cell variant. She had sign of upper airway obstruction for that tracheostomy done. Subsequently patient linked to oncology unit for radiation therapy.

Discussion: The primary symptom of anaplastic cancer is a rapidly enlarging neck mass. The thyroid enlargement is typically hard and nodular. Thyroid abscess is rare presentation of the tumor only one case report has been reported where anaplastic thyroid cancer mimicking thyroid abscess. This can be due to rapid growth of the tumor resulting in necrosis and superinfection of the cyst. (3) Other unusual presentations of the tumor has been reported including neck and thoracic cutaneous metastasis, concurrent hyperthyroidism and spontaneous intrathyroidal hemorrhage.(4,5,6) Diagnosis is commonly made by fine needle cytology although tissue biopsy needed if the diagnosis is not certain. Treatment of anaplastic thyroid cancer is multidisciplinary including surgery, radiotherapy and chemotherapy. Despite the treatment it is highly aggressive with poor outcome. In advanced disease airway protection and feeding access are important part of palliation.

POSTER 242

WITHDRAWN

POSTER 243

Thyroid Cancer Clinical Poster

THE TUMOR GROWTH MANIFESTED IN TWO‐FIFTHS OF LOW‐RISK PAPILLARY THYROID MICROCARCINOMA (PTMC) DURING ACTIVE SURVEILLANCE (AS): DATA FROM A MEDICAL CENTER IN CHINA

Kehao Le*, Lei Xie

Department of Head and Neck Surgery, The Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, China

OBJECTIVE: To assess the tumor growth by tumor doubling rate (TDR) during AS in China.

METHODS: Between January 2016 and June 2020, a total of 219 patients with low‐risk PTMC (aged 23‐75 years) were consecutively enrolled in the AS program.

RESULTS: Four sections of doubling rates were >0.5, 0.1 ∼ 0.5, ‐0.1 ∼ 0.1 and <‐0.1, corresponding to four categories of the tumor volume kinetics: rapid growth, slow growth, stable, and decrease in size. We found that 10.96% of PTMCs exhibited rapid growth, 31.96% exhibited slow growth, 27.4% were stable, and 29.68% exhibited decrease in tumor size. Tumor growth was associated with three factors: age, volume of PTMC at diagnosis and the number of ultrasonographic examination. 85% of elderly patients (≥ 60 years old) had tumors that remained stable or even shrank, and the rapid growth of the tumor was not found in them. As the follow‐up time extended, the proportion of tumor growth increased and the proportion of tumor non‐growth decreased. When the volume was small (≤14.13 mm3), the proportion of rapid growth was high (45.45%), and when the volume was large (> 179.5 mm3), the proportion of non‐ growth was 73.33%.

CONCLUSION: During the period of AS, the tumor growth condition of low‐risk PTMC should be evaluated by TDR. Ultrasound‐guided local hyperthermal ablation could be a good option especially for the PTMC patients with rapid or slow tumor growth.

POSTER 244

Thyroid Cancer Clinical Poster

ADVANCED THYROID CANCER IS ASSOCIATED WITH MULTIPLE DRIVER MUTATIONS INVOLVING DIFFERENT SIGNALING PATHWAYS

Deema Al‐Souri¹, Leonard Wartofsky¹, Kirk Jensen², Neelam Baral¹, Gretchen Hubbard³, Irina Veytsman¹, Vasyl Vasko², Kenneth Burman¹, Leila Shobab*¹

¹MedStar Washington Hospital Center, USA,²Uniformed Services University of the Health Sciences, USA,³Caris Life Sciences, USA

Background: Targeted therapy has emerged as a promising strategy for the treatment of aggressive thyroid cancer (TC). Choice of therapy is based on specific mutation identified frequently using a platform that tests a limited set of genes. The presence of multiple mutations could predict indication for combination drug therapy.

Objectives: To examine clinical and molecular characteristics of patients with advanced TC.

Material and Methods: Clinical, pathological and molecular data of 76 TC patients seen at two tertiary care centers were retrospectively analyzed. Patients with locally advanced, recurrent or metastatic disease were included. Molecular profiling was performed using whole exome sequencing platform by Caris Life Sciences.

Results: Average age at the time of surgery was 58 ± 15‐yr. There were 40 males and 36 females. There were 50 papillary TC (PTC), 11 follicular TC(FTC), 5 poorly differentiated TC (PDTC) and 10 anaplastic TC (ATC). Sixty patients (78.9%) had distant metastases (19 pulmonary, 26 pulmonary and bones, and 5 bone). Molecular analysis was performed in all cases and revealed 172 genomic alterations in 40 genes. The most common mutations were in BRAF (39/76 [51%]), RAS (21/76 [27.6%]), TERT (19/76 [25%]), TP53 (14/76 [18%], PTEN (8/76 [10.5%]. In addition, mutations in PI3KCA, ATM, ARID2, PDGFR, EGFR, RB1, MUTYH, PBMR1 were detected. In 5/76(6.5%) cases gene fusions involving RET, NTRK and BRAF were found. 25/76 (32.8%) tumors harbored only 1 driver mutation, and in 51/76 (67.2%) there were 2 or more mutations. In patients with locally advanced disease and those with distant metastases, 2+ mutations were detected in 9/16 (56.2%) and in 43/60 (71.6%) respectively. Co‐mutation in BRAF/TERT were detected in 10 cases (13%) and RAS/TERT in 6 (8%) cases. Three tumors harbored BRAF/RAS co‐mutations. We identified multiple mutations (up to 7 mutations) within the same tumors that involved different signaling pathways including BRAF/PI3CA, NRAS/MET/TP53 and BRAF/PTEN/TERT/KDM6A.

Conclusions: Aggressive TC is associated with multiple driver mutations involving different signaling pathways. Our results highlight the importance of utilizing multi‐gene panel‐based molecular testing for choice of targeted therapy in advanced TC. Given the co‐occurrence of mutations involving different signaling pathways, our results indicate the potential utility of combination‐treatment in advanced TC as a strategy to overcome drug resistance.

POSTER 245

Thyroid Cancer Clinical Poster

USING PREOPERATIVE ULTRASOUND VASCULARITY CHARACTERISTICS TO ESTIMATE MEDULLARY THYROID CANCER

Luying Gao*

PUMCH, China

Objective The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. According to ultrasound features, many MTC without suspicious ultrasound features were not categorized as high risk of malignancy. To comprehensively investigate the ultrasonic features of medullary thyroid carcinoma (MTC) on ultrasound and help screen thyroid nodules with identifying high risk of MTCs.

Methods Between 2019 and 2022, we identified sixty‐nine consecutive cases with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as “ultrasound‐high suspicious” (h‐MTC) and “ultrasound‐low suspicious” (I‐MTC). Using the same database, a tumor size and risk evaluation‐matched control group comprising 36 lesions was randomly selected, to compare the vascularity features of I‐MTC.

Results 51 h‐MTC (66.4%) and 18 I‐MTC (33.6%) were identified. For those with I‐MTC, 13/18 (72.2%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity was found in the I‐MTC Group than that in the Benign nodule Group (13/18, 72.2% vs 2/36, 5.6%, P < 0.001). We also showed that more CHAMMAS IV patterns (central blood flow greater than perinodular flow) (88.9% vs. 38.9%, P = 0.002)) and CHEN IV patterns (penetrating vascularity) (100% vs. 44.4%, P = 0.001) were found in I‐MTC than benign nodules. Preoperative serum calcitonin (Ct) was available in 49 cases, with every increment of stratified basal calcitonin level of 50, 200, and 500 pg/ml, there was no successive involvement of lymph node compartments (P > 0.05).

Conclusions Vascularity feature can help differentiate I‐MTC from benign nodules, moreover, we report a novel sonographic vascularity pattern of I‐MTC, penetrating branching vascularity. The utilization of vascularity feature will help to identify MTC among nodules with low‐intermediate suspicion of ultrasound risk classification, to ensure appropriate clinical management.

POSTER 246

Thyroid Cancer Clinical Poster

THYROSEQ V3 FOR IMPROVING THE MANAGEMENT OF INDETERMINATE THYROID NODULES (BETHESDA III AND IV): A PROSPECTIVE STUDY ON 500 PATIENTS IN A PUBLIC HEALTH CARE SYSTEM IN CANADA

Florence Lévesque*¹, Geneviève Rondeau², Danielle Beaudoin³, Pierre‐Hugues Fortier⁴, Marie‐Hélène Massicotte⁵, Marc Pusztaszeri⁶, Andrée Boucher², Richard J. Payne^7,8, Maryse Brassard⁹

¹Centre hospitalier de l'Université Laval, Canada,²Department of Endocrinology, Centre hospitalier de l'Université de Montréal, Canada,³Otolaryngology and Head and Neck Surgery divison, Department of Surgery, Centre hospitalier universitaire de Québec, Université Laval, Hôpital de l'Enfant‐Jésus, Canada,⁴Otolaryngology and Head and Neck Surgery Divison, Department of Surgery, Centre hospitalier de l'Univeristé de Sherbrooke, Canada,⁵Department of Endocrinology, Centre hospitalier de l'Université de Sherbrooke, Canada,⁶Department of Pathology, Jewish General Hospital, Canada,⁷Otolaryngology and Head and Neck Surgery divison, Department of Surgery, Jewish General Hospital, Canada,⁸Otolaryngology and Head and Neck Surgery divison, Department of Surgery, McGill University Health Centre, Canada,⁹Department of Endocrinology, Centre hospitalier de l'Université Laval, Canada

Objective: Around 20‐30% of thyroid nodules which undergo ultrasound guided fine needle aspiration fall into the Bethesda III and IV categories, indeterminate for malignancy. Diagnostic surgery is often used to manage these indeterminate thyroid nodules (ITN). The introduction of the next‐generation sequencing test ThyroSeq v3 (TSv3) in the clinical practice could reduce unnecessary treatment in a public health care system.

The primary objective of this study was to evaluate the clinical value of TSv3 by measuring the benign call rate (BCR), which refers to the proportion of negative results within the study population. To demonstrate its clinical value, the BCR should be ≥60%.

Methods: Under the guidance of the Quebec Health Ministry, we conducted a prospective study. The study included 500 consecutive patients with ITNs who underwent fine needle aspiration (FNA). FNAs were performed between January 2022 and November 2022. For patients with a negative test result, ultrasonographic studies were planned for a minimum of 2 years.

Results: A total of 500 patients underwent TSv3 testing, with 72.6% (363/500) obtaining a negative result (Bethesda III n = 224, Bethesda IV n = 139), and 27.4% (137/500) obtaining a positive result (Bethesda III n = 60, Bethesda IV n = 77). Among those who tested positive, the outcome as to whether the patient underwent surgery was known in 45% (62/137) of cases. 92% (57/62) of positive cases underwent surgery, while 8% (5/62) declined surgery. Among the patients who underwent surgery and had a positive TSv3 result, 66.7% (38/57) of the nodules were malignant or non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) (Bethesda III n = 12, Bethesda IV n = 26), and 33.3% (19/57) were found to be benign (Bethesda III n = 9, Bethesda IV n = 10). The mutations found in each category are described, with RAS‐like mutations being the most common in both malignant and benign tumors.

Discussion/Conclusion: 500 ITNs were assessed using TSv3, resulting in a BCR of 72.6%. This rate is higher than the BCR threshold of 60% pre‐established in the study, demonstrating that TSv3 for ITNs helped preventing an unnecessary surgery in most patients in our public health care system prospective cohort.

POSTER 247

Thyroid Cancer Clinical Poster

TWO‐STAGED RADIOACTIVE IODINE: A PROPOSED PROTOCOL FOR ADJUVANT RAI WHEN RECURRENT LARYNGEAL NERVE PALSY PRECLUDES COMPLETION THYROIDECTOMY

Tala Abu‐Hijleh*^1,2, Afshan Zahedi^1,2

¹University of Toronto, Canada,²Women's College Hospital, Canada

Introduction: Radioactive remnant ablation (RAI I131 therapy) has traditionally been reserved for DTC patients who have undergone total thyroidectomy. However, complications such as recurrent laryngeal nerve (RLN) injury or involvement of vital structures can make completion thyroidectomy a high morbidity procedure. Available literature has demonstrated use of radioactive lobar ablation in low risk DTC as a feasible and effective alternative to surgery with comparable rates of long term recurrence. However, to our knowledge there has been no published data on use of RAI therapy for both lobar ablation and treatment of known residual disease when completion thyroidectomy is not possible.

Case Description: We collected prospective data for a case series involving four patients treated at a tertiary center in Toronto, Canada between 2020‐2023. All four patients had high risk DTC post hemithyroidectomy, but completion thyroidectomy was not pursued due to RLN palsy. Patients were treated with an initial dose of RAI 30 mCi to achieve radioisotope lobar ablation. Successful ablation was inferred from post treatment TSH >25 mIU/ml, thyroglobulin (Tg), and I131 whole body scan (I131 WBS). Three months later they received a second RAI dose of 100mCi to treat residual disease. They underwent TSH suppression and q3‐6 monthly follow up to assess response to therapy as per American Thyroid Association 2015 guidelines. Followup has been conducted for two years and is currently ongoing. To date, 3 of 4 patients have demonstrated stable biochemical incomplete response and one patient has not yet completed treatment dose.

Discussion: Often, treatment options for patients with intact lobe and residual disease that is not resectable is limited and involves high morbidity and risk. This case series demonstrates a proposed two‐stage RAI protocol that can be used to achieve both lobar ablation and treatment of residual disease when surgery is not feasible. This provides a method to use RAI, a relatively low morbidity treatment and potentially extend progression free survival. Further studies and long term follow‐up is needed in this area.

POSTER 248

WITHDRAWN

POSTER 249

Thyroid Cancer Clinical Poster

IMPACT OF INCOME DISPARITY ON THYROID CANCER SURVIVAL AND SURGERY OUTCOMES: AN ANALYSIS USING SEER AND NRD DATABASES

Mohammad Hussein¹, Julia McGee*², Alexandria Luu², Michelle Tsang², Manal Malik², Eman Toraih¹, Emad Kandil³

¹Department of Surgery, Tulane University School of Medicine, USA,²Tulane University School of Medicine, USA,³Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, USA

Objective: Although the relationship between disparities and health outcomes of thyroid cancer patients has been studied, less is known about the specific effects of income inequalities on patient outcomes. Therefore, understanding the impact of income disparities in thyroid cancer care can improve patient care and reduce health inequities. The objective of the study was to evaluate the impact of income disparities on thyroid cancer survival, recurrence, and risk of secondary primary malignancy.

Methods: We conducted a retrospective analysis using (a) The Surveillance, Epidemiology, and End Results (SEER) database (2000‐2019) and (b) National Readmission Database (NRD) (2010‐2017). Patients were categorized into high and low annual household incomes at $75,000.Univariate, Logistic and Cox regression, and Kaplan‐Meier survival analyses were performed.

Results: A total of 139,302 SEER cases were analyzed. Higher‐income individuals (>$75,000) had a 26% reduced chance of recurrence (OR = 0.74, 95%CI = 0.55‐0.99, p = 0.042) and prolonged survival times compared to their lower‐income counterparts (18.1 years ±0.028 vs. 17.7 years ±0.022, p < 0.001). However, no differential risk of second primary malignancies was observed across different histological variants. Of the total 230,644 NRD cases, 171 (0.1%) developed complications, and 1,970 (0.9%) were readmitted. Higher income was associated with 49% (OD = 1.5, 95%CI = 1.10‐2.03, p = 0.009) and 24% (OD = 1.24, 95%CI = 1.13‐1.36, p < 0.001) decreased risk of postoperative complication and readmission within 30 days.

Conclusion: Our analysis of the SEER database revealed that higher‐income thyroid cancer patients had better survival outcomes and a reduced chance of recurrence. The NRD data showed that higher‐income cancer patients had decreased risk of postoperative complication and readmission within 30 days. These findings emphasize the importance of addressing income disparities in improving patient outcomes for thyroid cancer and ultimately informing policies that aim to reduce health inequalities and improve patient care.

POSTER 250

Thyroid Cancer Clinical Poster

ELUCIDATING THE LINK BETWEEN THYROID CANCER AND MERCURY EXPOSURE

Alyssa Webster¹, Dylan Pinion*¹, Mohamed Hussein², Eric Pineda¹, Manal Fawzy^3,4, Eman Toraih^2,5, Emad Kandil²

¹Tulane University School of Medicine, USA,²Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, USA,³Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Egypt,⁴Department of Biochemistry, Faculty of Medicine, Northern Border University, Saudi Arabia,⁵Medical Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Egypt

Objective: In this review and meta‐analysis, we seek to establish an association between the development of thyroid cancer and Hg exposure. A recent review of mercury (Hg) in cancer showed differing results regarding whether Hg can be considered a carcinogenic agent. The role of mercury in carcinogenesis remains unclear, although several identified mechanisms have suggested its involvement in specific cancers. Thyroid cancer (TC) incidence has surged recently, but data regarding mercury's influence on TC development is scarce. Mercury is involved in several molecular pathways implicated in carcinogenesis, and its proclivity for bioaccumulation in the thyroid suggests a potential modulatory effect.

Methods: We extensively reviewed the available literature, focusing on populations exposed to mercury, dietary exposure‐related TC risks, shared carcinogenic mechanisms between mercury and TC, and quantitative data connecting mercury exposure to TC. We included seven relevant studies between the years 1995 and 2022 in our meta‐analysis. The untransformed (raw) means for urinary and tissue Hg were estimated between thyroid cancer and non‐cancer groups using the inverse variance method and DerSimonian‐Laird estimator. We also compared global Hg emissions to global TC incidence using a the global UNEP mercury modelling report and the 2020 GLOBOCAN database.

Results: Insufficient evidence precludes definitive conclusions on dietary mercury as a TC risk factor; however, we identified several common mechanisms affected by mercury that are crucial for TC development, including biochemical, endocrine, and reactive oxygen species (ROS) effects. Our quantitative analysis revealed associations between TC risk and mercury exposure. In three mercury studies, average urine levels were higher in TC patients, with a mean difference of 1.86 μg/g creatinine (95% CI = 0.32–3.41). In one volcanic study and another investigating occupational exposure to elevated mercury levels, the exposed group exhibited a higher risk of developing TC, with a relative risk of 1.90 (95% CI = 1.76–2.06). In three thyroid tissue studies, mercury levels (ppm) were higher in TC patients, averaging 0.14 (0.06–0.22) in cancerous cases (N = 178) and 0.08 (0.04–0.11) in normal thyroids (N = 257).

Conclusion: Our findings suggest an association between mercury exposure and TC risk, implying a possible predisposing factor. Further research is necessary to reveal the clinical relevance of dietary and environmental mercury exposures in the pathogenesis of thyroid cancer.

POSTER 251

Thyroid Cancer Clinical Poster

CIRCULATING SMALL EXTRACELLULAR VESICLE‐BASED MIRNA CLASSIFIER FOR FOLLICULAR THYROID CARCINOMA: A DIAGNOSTIC STUDY

Genpeng Li*^1,2, Hongke Wang³, Jinjing Zhong⁴, Yilan Bai³, Wenjie Chen¹, Ke Jiang⁵, Jing Huang¹, Yuting Shao¹, Jiaye Liu¹, Yanping Gong⁶, Junhui Zhang⁷, Ronghao Sun⁸, Tao Wei¹, Rixiang Gong¹, Jingqiang Zhu¹, Zhi Lu³, Zhihui Li¹, Jianyong Lei¹

¹Division of thyroid, department of General Surgery, West China Hospital, Sichuan University, China,²The Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease related Molecular Network, West China Hospital, Sichuan University, China,³MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, China,⁴Department of Pathology, West China Hospital of Sichuan University, China,⁵Head and Neck Surgery, Sun Yat‐sen University Cancer Center, China,⁶Thyroid Surgery, West China Tianfu hospital, China,⁷Thyroid and Breast Surgery, West China fourth hospital, China,⁸Department of Head and Neck Surgery, Sichuan Provincial Cancer Hospita, China

Objective: The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. The present study was to evaluate the feasibility of circulating small extracellular vesicle (sEV)‐associated and cell‐free RNAs for noninvasive detection of FTC.

Methods: This multicenter diagnostic study involved 41 and 150 age‐ and sex‐matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating sEV‐associated and cell‐free RNAs, including long RNAs and microRNAs (miRNAs), were first compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real‐time polymerase chain reaction (qRT—PCR) assay, high‐quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression and stability of those candidates and the influence of the RNA classifier on the surgical strategy were also investigated in further tests.

Results: The diagnostic properties of sEV long RNAs, cell‐free long RNAs and sEV miRNAs were comparable for the detection of FTC and were superior to those of cell‐free miRNAs in RNA sequencing. Given the clinical application (sEV miRNAs are stable and easier to detect than long RNAs), the circulating sEV miRNA (CirsEV‐miR) classifier was developed from five miRNAs based on qRT—PCR data, which could well identify patients with FTC (AUC of 0.924 in the training cohort and AUC of 0.844 in the multicenter validation cohort). The CirsEV‐miR score was then calculated, which significantly correlated with the tumor burden and advanced stage of FTC. Additionally, the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue than in sEVs from the normal thyroid follicular epithelial cell line, organoid and tissue. Furthermore, circulating sEV miRNAs remained constant after pretreatment with RNase, prolonged exposure to room temperature or repeated freezing and thawing but were significantly reduced postoperation (thyroidectomy) and postradioiodine therapy. Finally, the addition of the CirsEV‐miR classifier as a biomarker improves the current surgical strategy.

Conclusion: Our study provided insight that the CirsEV‐miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.

POSTER 252

Thyroid Cancer Clinical

EFFECTS OF NEOADJUVANT CHEMORADIOTHERAPY ON ANAPLASTIC THYROID CARCINOMA: A SINGLE‐CENTER EXPERIENCE

Jin Seok Lee¹, Jun Sung Lee¹, Hojung Jeong*¹, Hyeok Jun Yun¹, Hoin Chang¹, Seok Mo Kim¹, Yong Sang Lee¹, Hang‐Seok Chang¹, Cheong Soo Park²

¹Gangnam Severance Hospital, Korea, Republic of,²CHA ilsan medical center, Korea, Republic of

Objective: Anaplastic thyroid carcinoma (ATC) is associated with the highest mortality risk of any thyroid‐arising tumor; however, there is currently no effective therapy for ATC, and multimodal therapy is associated with a relatively high mortality risk. Here, we investigated the effects of neoadjuvant chemoradiotherapy on patients with ATC treated with paclitaxel and intensity‐modulated radiation therapy (IMRT).

Methods: The medical records of 157 patients with ATC at Gangnam Severance Hospital were reviewed between January 2016 and November 2022. Only nine patients were eligible for surgery after neoadjuvant chemoradiotherapy according to the Gangnam Severance Hospital protocol for ATC.

Results: Seven patients were female, and two were male. The median age of the patients was 62 years (range: 53–76 years). The median tumor size of the patients was 3.94 cm (range: 2.1–5.6 cm). All the patients were treated with neoadjuvant paclitaxel and concomitant IMRT. The median number of cycles of neoadjuvant paclitaxel was 5 (range: 2–6 cycles) and the median IMRT dose was 5680 cGy (range: 5250–6600 cGy). Six patients showed a reduction in tumor size after neoadjuvant chemoradiotherapy. Three patients showed no significant differences or increases in tumor size after neoadjuvant chemoradiotherapy, but did display eminent tumor necrosis. Of the six patients with initial regional node metastasis, four showed a decrease in the size of metastatic nodes and internal necrosis. One patient had initial distant metastasis in the lung, and another showed newly diagnosed lung metastasis after neoadjuvant therapy. The mean interval from neoadjuvant radiation therapy to surgery was 93 days (range: 14–170 days). The median survival of patients with ATC who received neoadjuvant chemoradiotherapy was 358 days (range: 123–2,023 days).

Conclusion: Effective neoadjuvant chemoradiotherapy followed by complete surgical resection could be considered as one of the treatment options with prolonged median survival and safe local progression control.

POSTER 253

Thyroid Cancer Clinical Poster

HERBICIDE EXPOSURE IS ASSOCIATED WITH INCREASED THYROID CANCER RISK IN NEBRASKA

Siddhi Munde*¹, Azar Abadi², Whitney Goldner¹, Anupam Kotwal¹, Yeongjin Gwon¹, Jesse Bell¹

¹University of Nebraska Medical Center, USA,²University of Alabama at Birmingham, USA

The rate of thyroid cancer has been rapidly increasing since 2000. Thyroid cancer was the 12th most common cancer in the United States in 2021. The age‐adjusted incidence rate in Nebraska from 2014‐2018 was 15.4 compared to 14.1 for the United States. There is growing evidence that environmental endocrine‐disrupting chemicals (EDCs) impact thyroid function, and some studies indicate an increased risk for thyroid cancer. For example, thyroid cancer has been associated with pesticides like paraquat, metalaxyl, lindane, and atrazine. The associations between pesticide use and thyroid cancer in Nebraska have not been well‐studied. This study investigates the association between Nebraska's most widely applied pesticides and thyroid cancer incidences.

The data for thyroid cancer per ICD code was obtained from Nebraska Cancer Registry. County‐level pesticide use data were obtained from USGS Pesticide National Synthesis Project. The total thyroid case count for individuals over 35 years of age at diagnosis was calculated by county. Based on a 20‐year temporal lag, we evaluated the association between county‐level total thyroid cancer cases from 2012‐2014 with average pesticide use from 1992‐ 1994. The statistical analysis was implemented using a negative binomial distribution model.

We found statistically significant associations between thyroid cancer and paraquat individually and combined with other pesticides. With one ton increase in paraquat application, we observed positive association with Incidence Risk Ratio (IRR) 1.18 (95%CI [1.08‐1.30]) for thyroid cancer. We also found increase in IRR of 1.36 (95%CI [1.07‐1.75]) for thyroid cancer with 1 ton application of paraquat when adjusted with glyphosate. Also, on adjusting for urbanicity in the model, we found an increased risk for thyroid cancer with paraquat use with 20‐year lag. Our results show a 36% increase in risk of thyroid cancer per ton of application two commonly used herbicides. For future work, we intend to evaluate temporal lag of five and ten years to assess similar patterns with pesticide use. These results will help in understanding environmental exposures that could lead to a greater likelihood of cancer and assist with educating those at higher risk of exposure.

POSTER 254

Thyroid Hormone Action Metabolism and Regulation Basic Poster

DISSECTING THE PEDIATRIC THYROID TO THE SINGLE CELL

Erin Reichenberger*, Julio Ricarte Filho, Aime Franco

Children's Hospital of Philadelphia, USA

Single‐cell/nucleus RNA‐sequencing (scnRNA‐seq) grants researchers the ability to view the individual transcriptional portraiture of thousands to millions of cells. This has provided insight into the heterogeneity in tissue composition, identified rare cell types, determined cell lineage, and advanced our understanding of biological processes [1,2,3].

The thyroid is a bi‐nodule gland that plays an integral part in regulating signaling within the human body via hormones produced by follicular cells and c‐cells. These hormones are essential for normal pediatric development and are modulators of both innate and adaptive immune responses. While it is known that the innate and adaptive immune systems are crucial to maintaining homeostasis, organ development, and metabolism, it has not been fully established which immune cells are present or in what proportions, how many sub‐types there are, or their behavior in healthy pediatric thyroids and in pediatric papillary thyroid cancers with different genomic drivers (fusions versus BRAF).

Here we use the scTinker single cell pipeline to analyze multiple human pediatric thyroid tissue samples. The scTinker pipline is an open‐sourced and automated pipeline that can be tailored with user‐defined parameters to better suit specific biological questions and sampled tissue without previous knowledge of the tissue's cellular compositions or behavior. Depending on chosen parameters, the pipeline will produce multiple clustering schematas that can be compared in a visual interactive report. This pipeline includes typical scnRNA‐seq workflow operations (data quality control, dimensionality reduction and imputation, clustering, differential gene expression analysis, and gene set enrichment analysis). This workflow will characterize all major cell types as well as subgroups in pediatric healthy and diseased thyroid tissue while assessing the relationship between hormone expression and immune cell presence and behavior.

POSTER 255

Thyroid Hormone Action Metabolism and Regulation Translational Poster

BRANCHED‐CHAIN AMINOACIDS, ALANINE AND THYROID FUNCTION: AN NMR‐BASED APPROACH FROM ELSA‐BRASIL

Carolina Janovsky*^1,2, Marina Birck², Vandrize Meneghini², João Roberto Martins¹, José Augusto Sgarbi^1,3, Patricia Teixeira⁴, Paulo Lotufo², Isabela Bensenor²

¹UNIFESP, Brazil,²USP ‐ CPCE, Brazil,³Faculdade de Medicina de Marília, Brazil,⁴UFRJ, Brazil

OBJECTIVE: Branched‐chain amino acids (BCAAs) are essential amino acids that may play a role not only in protein synthesis but also in intracellular metabolism, including thyroid dysfunction. Our aim was to evaluate BCAA and alanine levels according to TSH, Free‐T4 (FT4) and Free‐T3 (FT3) levels.

METHODS: We included 13,632 individuals from the ELSA‐Brasil study that had serum TSH, FT4 e FT3 measured at baseline. BCAA (valine, leucine, isoleucine) and alanine were evaluated by nuclear magnetic resonance (NMR) spectroscopy. The association between the aminoacids' levels and thyroid tests was evaluated using linear regression models with TSH, FT4 and FT3 as continuous variables and by quintiles, using the 3rd quintile as reference. The association was considered statistically significant if p < 0.05.

RESULTS: We evaluated 4553 individuals (54.1% women, 51.2% white, mean age 50.6 ± 8.7 years). Considering TSH levels, when evaluated as a continuous variable (log‐transformed), BCAA levels' coefficient rises as log‐TSH rises in the univariate analysis, as well as isoleucine and alanine. However, after adjustments for demographic factors and comorbidities, only alanine's rise remains statistically significant (p < 0.001). When divided by quintiles, alanine levels remain consistently low in the first quintile, even after adjustments. When analyzing free T4 levels, alanine and isoleucine coefficients decrease as FT4 levels rise as continuous variable. When divided by quintiles, alanine levels are persistently high in the first quintile, even after multi‐adjustments. Considering FT3 levels, there is a significant and consistent rise in valine, leucine and general BCAA coefficient as continuous FT3 increases (p < 0.001). When distributed by quintiles, after multivariate analysis, alanine levels remain low in the first quintile, valine levels are lower in the first quintile and higher in the fifth, as well as BCAA levels (p = 0.030, p = 0.001 and p = 0.007 respectively).

CONCLUSIONS: Alanine was consistently associated with thyroid function, positively associated with TSH and negatively with FT4, when the variables were used continuously or by quintiles. Free T3 levels were positively associated with BCAA when used continuously or by quintiles. Alanine had a negative association with FT3 levels, with significant lower levels at the first quintile compared to the third.

POSTER 256

Thyroid Hormone Action Metabolism and Regulation Clinical Poster

HYPOTHYROIDISM IN TOTAL THYROIDECTOMIZED PATIENTS: THE ROLE OF ORAL LIQUID L‐THYROXINE (L‐T4)

Poupak Fallahi¹, Francesca Ragusa*², Silvia Martina Ferrari³, Giusy Elia², Gabriele Materazzi², Armando Patrizio⁴, Sabrina Rosaria Paparo¹, Valeria Mazzi², Paolo Miccoli², Alessandro Antonelli²

¹University of Pisa, Department of Translational Research of New Technologies in Medicine and Surgery, Italy,²University of Pisa, Department of Surgical, Medical, Molecular Pathology and Critical Area, Italy,³University of Pisa, Department of Clinical and Experimental Medicine, Italy,⁴Department of Emergency Medicine, Azienda Ospedaliero‐Universitaria Pisana, Italy

Objectives: Tablet formulation of levothyroxine (L‐T4) represents the treatment of choice for hypothyroidism. We aim to investigate the efficacy of liquid formulation compared to tablets of L‐T4 in patients recently submitted to total thyroidectomy and without malabsorption or drugs interference.

Methods: Eighty‐five patients were assigned to L‐T4 in tablets, whereas one hundred‐seventy received liquid L‐T4 at the same substitutive dosage (1.5 mcg/kg/day). All patients began the therapy the day after thyroidectomy, and it was taken every day 30 min before breakfast. Serum thyrotropic hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured at 6 weeks (first control), and, later, after 12 weeks (second control).

Results: There was a significant higher number of patients with TSH level above than normal range (TSH >3.6 mcU/ml) while taking L‐T4 tablet therapy, than among those treated with the L‐T4 liquid formulation. Indeed, TSH values were significantly lower in the liquid L‐T4 formulation group, than in the tablet formulation L‐T4 group both at the first (P < 0.05), and at the second control (P < 0.01). There was no significant difference of the FT4 and FT3 levels between the two groups.

Conclusion: Our results suggest that liquid L‐T4 therapy leads to a better control of TSH levels in thyroidectomized patients with no history of malabsorption and gastric disorders or ingestion of concomitant interfering drugs.

POSTER 257

Thyroid Hormone Action Metabolism and Regulation Clinical

ASSOCIATION BETWEEN THYROID FUNCTION AND SARCOPENIA AND ITS COMPONENTS OF ELDERLY PEOPLE IN RURAL CHINA

lina zhang*

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, China

Purpose: The association between thyroid function and sarcopenia and its components of elderly in rural China remains unclear. This study aimed to evaluate the effect of thyroid function on sarcopenia and its components of elderly in rural China.

Methods: Two hundred and forty elderly people in rural areas of China were included in this study and were divided into normal and sarcopenic groups. Free triiodothyronine (FT3), free thyroid hormone (FT4) and thyroid stimulating hormone (TSH) levels were measured by electrochemiluminescence, upper limb grip strength was measured by JAMAR grip strength meter and extremity muscle content (ASM) was assessed by bioelectrical resistance group.

Results: Of the 240 subjects in this study, 52 cases were diagnosed with sarcopenia and the prevalence of sarcopenia was 21.67%, of which, 33 (31.13%) were males and 19 (14.18%) were females. The prevalence of sarcopenia gradually elevated with increasing age. The TSH level in the sarcopenia group was significantly higher than that in the normal control group, and there was no significant difference in FT3 and FT4 levels between the two groups. Subclinical hypothyroidism was significantly associated with sarcopenia, while FT3, FT4 and TSH levels were not associated with sarcopenia. Subclinical hypothyroidism was associated with low grip strength and low ASM, but not with low somatic function. FT3 levels were positively correlated with grip strength and ASM, FT4 levels were positively correlated with ASM, and TSH levels were negatively correlated with grip strength, 6m step speed, and SPPB scores, and positively correlated with time to 5 sit‐up tests.

Conclusion: Subclinical hypothyroidism is a potential risk factor for sarcopenia and is associated with low grip strength and low ASM, but not with low physical function. FT3, FT4 and TSH level were only associated with the sarcopenia component, but not with sarcopenia.

POSTER 258

Thyroid Imaging Case Study Poster

THYROID BED EXTENSION OF THYROID MASS COMPLICATED BY TRACHEAL STENOSIS FROM MASS EFFECT

Sakshi Sharma*, K. Romo, Qasim Iqbal

Ochsner Clinic Foundation, USA

Introduction: A goiter is defined as an enlargement of the thyroid gland regardless of etiology. Goiters can be seen in patients that are hyperthyroid, hypothyroid, or euthyroid. The thyroid bed is the space where the thyroid gland is situated adjacent to the larynx and trachea, with its upper margins near the oblique line of the thyroid cartilage and lower margin at the level of the fourth‐ fifth tracheal cartilage. Extension outside the thyroid bed is determined by the space around the thyroid gland. Substernal goiters are extensions with direct downward growth into pretracheal space. The following presents a case of a woman with thyroid nodules with prior nodulectomy found to have thyroid bed extension.

Description of the Case: A 61‐year‐old female with multiple bilateral thyroid nodules s/p excision of benign right inferior thyroid nodule who presents with dysphagia, globus sensation, hoarseness, and dyspnea on exertion. Vitals normal on room air. Physical exam with diffuse thyromegaly. TSH 1.717 (nl 0.4‐4.0). Thyroid ultrasound revealed 2.3 cm TR4 mid right nodule, 3.5 cm TR3 lower right thyroid nodule, and 4.7 cm right thyroid nodule that was incompletely visualized extending substernally. A stable left thyroid nodule measuring 1.6 cm was also noted. CT Chest showed inferior thyroid bed mass extending into right superior mediastinum and tracheal stenosis due to mass effect. She was evaluated by ENT, Thoracic Surgery, and Cardiac Surgery. The substernal intrathoracic portion of thyroid goiter will be excised, and the upper portion of the substernal component will require dissection from the cervical approach for complete resection.

Discussion: This case presents a patient who had previously undergone a right thyroid nodulectomy instead of formal lobectomy and had subsequently developed thyroid extensions outside the thyroid bed complicated by tracheal stenosis from mass effect. Goitrous extensions often do occur outside the thyroid bed, and are more likely to happen in women. This report highlights the importance of evaluating extensions outside of the thyroid bed and developing a multidisciplinary approach with thoracic and endocrine surgeons to surgically remove symptomatic extensions.

POSTER 259

WITHDRAWN

POSTER 260

Thyroid Imaging Clinical Poster

MULTIPARAMETRIC ULTRASOUND TECHNIQUES ARE SUPERIOR TO AI‐ASSISTED ULTRASOUND FOR ASSESSMENT OF SOLID THYROID NODULES: A PROSPECTIVE STUDY

Yingying Li*, Mingbo Zhang, Yukun Luo

Chinese PLA General Hospital, China

Objectives: To evaluate the diagnostic performance of multiparametric ultrasound (mpUS) and artificial intelligence assisted B‐mode ultrasound (AI‐US), and their potential to reduce unnecessary biopsies to B‐mode for solid thyroid nodules.

Methods: This prospective study enrolled 226 solid thyroid nodules with 145 malignant and 81 benign pathological results from 189 patients (35 men and 154 women; age range, 19‐73 years; mean age, 45 years). Each nodule was examined using B‐mode, microvascular flow imaging (MVFI), elastography with elasticity contrast index (ECI), and an AI system based on B‐mode images. Image data were recorded for each modality. Ten readers with different experience levels independently evaluated the B‐mode images of each nodule to make a “benign” or “malignant” diagnosis in both an unblinded and blinded manner to the AI reports. The most accurate ECI value and MVFI mode were selected and combined with the dichotomous prediction of all readers. Descriptive statistics and AUCs were used to evaluate the diagnostic performances of mpUS and AI‐US.

Results: Triple mpUS with B‐mode, MVFI, and ECI exhibited the highest diagnostic performance, with an average AUC, sensitivity, and specificity of 0.811, 87%, and 75%, respectively. Compared with the B‐mode (average AUC, sensitivity, and specificity were 0.677, 92%, and 43%, respectively), the specificity and AUC were significantly improved (both P < 0.01). AI‐US showed the second‐best diagnostic performance with an average AUC, sensitivity, and specificity of 0.718, 86%, and 58%, respectively. Triple mpUS showed higher sensitivity, specificity, and AUC than AI‐US (87% vs. 86%, 75% vs. 58%, and 0.811 vs. 0.718, respectively), among which the specificity and AUC were statistically different (both P < 0.05). Compared with B‐mode, both triple mpUS and AI‐US reduced the unnecessary biopsy rate by 12% (P = 0.007) and 4.3% (P = 0.352), respectively, but the latter showed no statistical difference.

Conclusions: Compared to AI‐US, triple mpUS (B‐mode, MVFI, and ECI) exhibited better diagnostic performance for thyroid cancer diagnosis, and resulted in a significant reduction in unnecessary biopsy rate. Multiparametric ultrasonography (B‐mode ultrasonography combined with MVFI and elastography) can provide morphological and functional information to assist in the comprehensive diagnosis of thyroid cancer and can significantly reduce unnecessary thyroid nodule biopsies with higher diagnostic performance compared with AI based on B‐mode ultrasonography in this study. Therefore, we believe that when diverse ultrasonographic imaging modalities are taken advantage by AI networks, AI system could achieve higher diagnostic performance which can facilitate thyroid cancer diagnoses and reduce unnecessary biopsies in clinical practice.

POSTER 261

Thyroid Nodules and Goiter Case Study Poster

COEXISTENCE OF FOLLICULAR ADENOMA AND NECROTIZING GRANULOMA OF THYROID NODULE

Nandar Mon*, Rahul Pansare, Mahsa Javid, Zakaria Sibai, Sri Prakash Mokshagundam

University of Louisville, USA

Introduction: Thyroid nodule with necrotizing granulomatous finding is a rare condition. The etiologies include tuberculous and fungal infections, granulomatosis with polyangiitis, plasma cell granuloma, post‐surgical/palpation thyroiditis and, rarely, sarcoidosis which usually causes non‐necrotizing granulomas. We report a rare case of concurrent follicular adenoma and necrotizing granuloma of thyroid gland.

Case description: A 39‐year‐old African American woman presented with 10 months history of non‐toxic thyroid nodules. She reported palpitations, irritability, dizziness, inability to focus at times, occasional hoarseness, and difficulty swallowing, but no difficulty breathing. She has no history of radiation to the head and neck, autoimmune and infiltrative disease. She did not travel outside the United States. Review of systems was unremarkable. Her medical history was significant for type 2 diabetes mellitus and obesity class 3. She smokes cigarettes but denied alcohol and illicit drug use. She works as a school bus driver. Physical exam was remarkable for morbid obesity and non‐tender palpable thyroid nodules on the left side. Laboratory tests showed TSH 1.14 mIU/L (0.4‐4.5 mIU/L), Free T4 1.1ng/dL (0.8‐1.8ng/dl), Total T3 123 ng/dL (76‐181 ng/dl), negative Thyrotropin receptor and TPO antibodies, normal CBC and CMP. Thyroid ultrasound revealed complex bilateral nodules, largest on the right measuring 0.96cm and on the left measuring 6.2x3.2x4.1cm. FNA of left lobe thyroid nodule reported Bethesda Category II, follicular cells, colloid and some macrophages present, findings compatible with a benign follicular nodule. However, she underwent left lobectomy and isthmusectomy for substernal extension of left thyroid nodule with compression symptom. Histopathology revealed a 5 cm follicular adenoma and a necrotizing granuloma. GMS and AFB special stains did not reveal any microorganisms. Serum Aspergillus Galactomannan Antigen and Urine Histoplasma Galactomannan Antigen were negative. She recovered uneventfully.

Discussion: Necrotizing granuloma and follicular adenoma of thyroid gland coexist in our euthyroid patient. The etiology of the necrotizing granuloma remains unclear. Only one previous case has been reported with idiopathic necrotizing granuloma of thyroid gland with hypothyroid symptoms. To our knowledge, this is the first case report of both pathologies in a thyroid gland.

POSTER 262

Thyroid Nodules and Goiter Case Study Poster

LASER ABLATION THERAPY FOR BENIGN LARGE THYROID NODULES: SIX‐MONTH OUTCOMES OF TWO SENIOR PATIENTS

Niketa Kalara*, Crystal Acosta, Alex Manzano

Mount Sinai Medical Center, USA

In clinical practice, thyroid nodules are commonly seen in adults with a prevalence of 20‐76% based on ultrasound and 3‐7% based on palpation. Nodules causing cosmetic concerns or compressive symptoms need treatment. In recent years, ultrasound (US) guided percutaneous laser ablation (PLA) has been approved in the USA for treating benign thyroid nodules. Here we discuss the 6‐month follow‐up outcomes of 2 cases of older individuals treated with PLA.

Case 1 is a 75‐year‐old female, biochemically euthyroid, with a history of multinodular goiter presented with concerns of neck fullness and discomfort, with a cosmetic score of 3/4. US findings suggested multinodular goiter with the largest nodule measuring 2.8x1.13x3cm (volume:4.96 mL), cystic and solid, hypoechoic, wider than tall, ill‐defined margins, TIRADS 6 in the left inferior lobe. Two FNA biopsies were benign. She declined surgery so PLA was scheduled. A total of 1550 Joules were delivered using one fiber. Six months post‐ablation, the nodule measured 1.44x1.03x1.55cm (1.21mL) with 75% volume reduction and a cosmetic score of 1/4 plus improved symptomatology.

Case 2 is a 69‐year‐old female, biochemically euthyroid, with a history of multinodular goiter status post‐left thyroidectomy more than 30 years ago in Nicaragua, presented for evaluation of nonsurgical intervention of right thyroid nodules that had been causing local discomfort, including dysphagia with a cosmetic score of 3/4. US showed multinodular goiter in the right lobe with the dominant nodule measuring 2.6x2x3cm (volume:7.7mL), isoechoic, TIRADS 4. Two FNA biopsies were benign. PLA was performed using one laser fiber delivering 1610 Joules. Six months post‐ablation, the nodule showed a 51% reduction measuring 1.97x1.8x2.06 (3.84mL), improving the cosmetic score to 1/4.

PLA is a safe, non‐surgical approach for managing benign thyroid nodules with promising results. Some of the inclusion criteria are two benign FNA biopsies 3‐6 months apart and a nodule size of more than 2.5 cm. The aim is to have a more than 50% volume reduction in twelve months. In both cases, the patients declined surgery; thus, PLA was successfully done, with more than 50% volume reduction, resolution of compressive symptoms, and improved cosmetic appearance.

POSTER 263

Thyroid Nodules and Goiter Clinical Poster

EVALUATION OF SAFETY AND SHORT‐TERM EFFICACY OF MICROWAVE ABLATION FOR BENIGN THYROID NODULES; PRELIMINARY DATA

Hossam Ghazi*

Mansoura Faculty of Medicine, Egypt

Objective: Benign thyroid nodules are frequently seen during scanning by neck ultrasound. Unless they are causing compressive or cosmetic symptoms, no intervention nor medical treatment is required. Till few years ago, thyroidectomy is the only available treatment. Microwave Ablation (MWA) is recently approved method causing thermal necrosis of thyroid nodule leading to improvement of cosmetic & compressive symptoms. The aim of the current study was to evaluate short term safety and efficacy of MWA in treating benign thyroid nodules. Methods: we included 30 patients in our study (4 of them were males) with mean age 27.6 years (ranging from 18 to 62 years). All patients are euthyroid apart from 6 patients having Autonomous Functioning Toxic Nodules(AFTN). Volume Reduction Rate (VRR), cosmetic and compressive symptoms were measured at baseline and after 1 month & 3 months. Moreover, Hamilton Anxiety Rating Scale (HAMA‐A) was assessed before and 3 months after MWA. Results: The mean initial volume of the nodules was 36.4 + 18.69 ml. The mean VRR was 49.66 + 28.78 % and 66 + 23.09 after 1 month and 3 months consecutively. Cosmetic and compressive scores were significantly improved. Similarly, HAMA‐A significantly improved after 3 months. All patients with AFTN turned euthyroid after 3 months. Only one patient developed transient hoarseness of voice which improved after few days. Conclusion: MWA is a safe and effective procedure to treat benign thyroid nodules and could be an alternative to thyroidectomy operated just under local anesthesia without any scars or injury to parathyroid glands.

POSTER 264

Thyroid Nodules and Goiter Clinical Poster

THE RELATIONSHIP BETWEEN VITAMIN D NUTRITIONAL STATUS AND ULTRASOUND CLASSIFICATIONS OF THYROID NODULES IN YOUNG AND MIDDLE‐AGED EUTHYROID MALE PETROLEUM WORKERS

Deping Wang*^1,2, Jing Li¹, Dongdong Luo^1,3, Song Leng³, Bingrui Gao¹, Zhongyan Shan¹, Weiping Teng¹, Jialin Hu⁴, Chenxi Zhang⁵, Bojuan LI¹, Zhaoying Chen¹

¹Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affifiliated Hospital of China Medical University, China,²Department of Endocrinology and Metabolism, Hongqi Hospital Affiliated to Mudanjiang Medical College, China,³The Second Affiliated Hospital of Dalian Medical University, China,⁴Liaoning University of Traditional Chinese Medicine, China,⁵Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, China

Objective: This study was aimed to analyze the relationship between vitamin D (VD) nutritional status and the occurrence risk of thyroid nodules (TNs) in young and middle‐aged euthyroid male (YMAEM) petroleum workers without thyroid autoimmunity (TAI).

Methods: A retrospective analysis was conducted on the health check‐up database from 2037 YMAEM petroleum workers without TAI aged 30 to 60 years. Serum 25(OH)VD, 25(OH)VD3 and 25(OH)VD2 levels were assayed by liquid chromatography‐tandem mass spectrometry. The participants were classified into different groups according to their ultrasound images of TNs based on Chinese‐Thyroid Imaging Reporting and Data System (C‐TRIADS). C‐TRIADS consist of 6 grades, and the upper three indicate TNs with potential malignancy.

Results: No C‐TRIADS 5 or 6 nodules were found in these participants. Serum 25(OH)VD level in the C‐TIRADS 4 TN group [17.59 (12.64‐23.72) ng/mL] were significantly lower than that in the C‐TIRADS 1 [23.68 (18.04‐30.19) ng/mL, P < 0.05], C‐TIRADS 2 [24.65 (19.33‐29.82) ng/mL, P < 0.05], and C‐TIRADS 3 groups [25.06 (19.94‐30.79) ng/mL, P < 0.05]. The overall prevalence of TNs was similar among VD‐ deficient [25(OH)VD <20 ng/ml, 53.8%], insufficient [20 ≤ 25(OH)VD <30 ng/mL, 55.4%] and sufficient groups [25(OH)VD ≥30 ng/mL, 52.4%]. The relative proportion of the patients with C‐TIRADS 4 TNs was markedly higher in the VD deficiency group (34.3%) than in insufficient (9.9%, P < 0.05) and sufficient groups (7.9%, P < 0.05). Identical findings were observed among the groups with low, medium and high serum 25(OH)VD3 levels, but not among those with different serum 25(OH)VD2 levels. Based on all the participants, a binary logistic regression analysis exhibited that VD insufficiency [OR = 0.273 (95% CI: 0.191‐0.391; P < 0.001)] and sufficient status [OR = 0.199 (95% CI: 0.122‐0.325, P < 0.001)] resulted in a significantly reduced risk of developing C‐TIRADS 4 TNs when compared with that of VD deficiency.

Conclusions: VD deficiency is an independent risk factor for the development of TNs with malignant ultrasound characteristics in YMAEM petroleum workers without TAI. VD3 rather than VD2 supplement may reduce the occurrence of TNs with malignant ultrasound characteristics among those men.

POSTER 265

Thyroid Cancer Basic Poster

METABOLIC PLASTICITY IS ONE OF THE MECHANISMS OF THYROID CANCER RESISTANCE TO LENVATINIB

Sonam Kumari*, Shilpa Thakur, Stephanie Cardenas, Andrew Makarewicz, Joanna Klubo‐Gwiezdzinska

National Institutes of Health, USA

Objective: Lenvatinib is an FDA‐approved tyrosine kinase inhibitor (TKI) used for the treatment of metastatic radioactive iodine (RAI) non‐responsive progressive thyroid cancer (TC). The objective response rate to Lenvatinib of 65% is non‐durable, and most patients develop resistance to therapy with Lenvatinib. Given a well‐established clinical phenomenon of RAI‐non‐responsive thyroid cancer being characterized by a higher glucose uptake evidenced by fluorodeoxyglucose positron emission tomography imaging, we hypothesized that glucose metabolism might play a role in resistance to TKIs.

Methods: We used two human Lenvatinib sensitive (LS) TC cell lines THJ29T and TPC1 and induced Lenvatinib resistance (LR) through continuous exposure to increasing concentrations of the drug. A resistance factor of ≥2 was attained in the LR cells. The LR cells phenotype was assessed through analysis of cell cycle and apoptosis rate, that were quantified with flow cytometry. Immunoblot was performed to analyze the expression of components of mitochondrial respiratory chain. Aerobic glycolysis was measured via Seahorse XF Cell Mito Stress Kit, that quantifies mitochondrial oxidative phosphorylation (OXPHOS) in glucose‐rich conditions. A p‐value of ≤0.05 was considered statistically significant.

Results: LR TC cells are characterized by either a similar cell cycle pattern or enhanced G2‐M phase of cell cycle as compared with LS cells, revealing a pattern promoting mitosis and proliferation. There was a lower early apoptosis rate in treated with lenvatinib LR vs LS cells (THJ29T: 0.41 ± 0.03 vs 0.8 ± 0.1, p = 0.001, TPC1: 0.40 ± 0.02 vs 0.81 ± 0.12, p = 0.003). There was a significant upregulation of the protein expression of mitochondrial respiration markers: complex I NDUFB8, complex II SDHB, complex III UQCRC2, complex IV COX II, and complex V ATP5A in LR cells as compared with LS‐TC. Consistently, LR cells were characterized by a significantly increased maximal mitochondrial oxygen consumption rate as compared with LS cells (THJ29T‐LR 4013 ± 306 vs THJ29T‐LS 2293 ± 334, p < 0.001; TPC1‐LR 3999 ± 358 vs TPC1‐LS 1774 ± 208, p < 0.0001).

Conclusions: Enhanced mitochondrial respiration is one of the contributing factors towards resistance to Lenvatinib. Combination therapies including OXPHOS inhibitors should be tested as potential avenues to overcome metabolic resistance mechanisms.

POSTER 266

Thyroid Cancer Basic Poster

TR3 PROMOTES ANAPLASTIC THYROID CANCER PROGRESSION BY ENHANCING NRF2 SIGNALING AND IS CORRELATED WITH POOR PROGNOSIS

Tinglin Yang*, Wenhui Li, Chen Chen, Tao Huang

Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China

Objective: Anaplastic thyroid cancer (ATC) is the most aggressive subtype of thyroid cancer with an elevated mortality rate. Orphan Nuclear Receptor TR3 has been reported in various kinds of malignancies, however, whether it involves in ATC remains unknown. This study aimed to investigate the function and mechanism of TR3 in ATC tumorigenesis and its association with prognosis.

Methods: Quantitative real‐time PCR was conducted to detect TR3 expression, and Kaplan‐Meier survival analysis was carried out to determine the connection between TR3 and prognosis. To explore the function of TR3, stable knockdown was performed by lentiviral infection in ATC cell line 8505C. Cell counting kit‐8 (CCK‐8) assays and wound healing assays were subsequently exploited. RNA sequencing and KEGG analysis were utilized to identify genes and pathways regulated by TR3.

Results: TR3 exhibited aberrantly high expressions in ATC cells compared to normal thyroid cells. Kaplan Meier plots indicated high expression of TR3 was correlated with decreased survival rates in thyroid cancer patients, presenting a negative association between TR3 expression level and prognosis (HR = 3.9, p‐value = 0.035). The knockdown of TR3 significantly attenuated cell proliferation and migration in 8505C cells. RNA sequencing and transcriptomic analysis identified a total of 1071 differentially expressed genes (DEGs), including 733 upregulated genes and 338 downregulated genes (p‐value <0.05, |log2FoldChange| > 1.0). KEGG analysis revealed the accumulation of DEGs leads to a more than 2‐fold downregulation in the Nrf2 signaling pathway, a typical pathway that has been reported to motivate thyroid cancer progression. Taken together, the knockdown of TR3 ameliorated ATC cell proliferation and migration mainly by suppressing the Nrf2 signaling.

Discussion: Our study revealed TR3 plays an important proto‐oncogenic role in ATC via modulating Nrf2 signaling, and high expression levels of TR3 indicate poor prognosis in thyroid cancer. Recently, increasing evidence has shown the therapeutic potential of agents targeting TR3 as an antitumor treatment. Results from our study provide a theoretical basis for clinical applications of novel TR3 antagonists in ATC therapy.

POSTER 267

Thyroid Hormone Action Metabolism and Regulation Basic

DEFECTS IN THYROID HORMONE TRANSPORTER DUE TO SLC7A5 KNOCKOUT CAUSES PANETH CELL DEDIFFERENTIATION TOWARD STEM CELLS

lingyu bao*, yun‐bo shi, Zhaoyi peng

NIH, USA

Paneth cells located the intestinal crypts function as stem cell niche and contribute to stem cell survival and regeneration. By using a conditional knockout mouse line, we show here that solute carrier family 7 member 5 (slc7a5), which mediates the uptake of large neutral amino acids (LNAAs) and thyroid hormone, is critical for stem cell niche homeostasis. Inactivation of slc7a5 gene in intestinal epithelia resulted in a dramatical loss of lysozyme expression in Paneth cells at both RNA and protein levels and increased cell proliferation in the crypt base where Paneth cells and stem cells reside. In addition, slc7a5 knockout increased the proliferation but not the number of Lgr5‐positive crypt base stem cells and increased the number and proliferation of transit amplifying cells, which are descendants of Lgr5‐positive stem cells. These suggest that slc7a5 defect enhanced the proliferating Lgr5 stem cell to become transit amplifying cells. On the other hand, by using electronic microscopy, we found that Paneth cell numbers did not decrease significantly despite the drastic reduction in expression of lysozyme, a marker for differentiated Paneth cells, suggesting loss of differentiation of the Paneth cells in knockout intestine. Furthermore, we performed single cell RNAseq and found that Paneth cells in wild type mice and epithelial slc7a5 knockout mice formed two distinct clusters with distinct feature genes. The top 20 feature genes highly expressed in wild type Paneth cells are enriched with secreted protein genes, while those highly expressed in slc7a5 knockout Paneth cells are enriched with ribosomal genes, which are associated with regeneration and increased cell stemness. These novel findings led us to hypothesize that the loss of slc7a5 in intestinal epithelial cells causes Paneth cells to dedifferentiate toward stem cells and promote stem cell proliferation. To test our hypothesis, we are performing lineage‐tracing studies in vivo and co‐cultures of Paneth cells and stem cells from wild type and slc7a5 knockout in in vitro organoid assays to determine if Paneth cells can dedifferentiate into stem cells and whether slc7a5 knockout affects this process. To further test if the Paneth cell dedifferentiation is mediated by thyroid hormone, we are performing adding thyroid hormone, PTU(propylthiouracil) or slc7a5 transporter inhibitor to organoids from wild type and slc7a5 knockout to verify the phenotype in vitro.

POSTER 268

Thyroid Hormone Action Metabolism and Regulation Basic Poster

PROTEIN ARGININE METHYLTRANSFERASE 1, A COACTIVATOR FOR THYROID HORMONE RECEPTOR, REGULATES ADULT INTESTINAL EPITHELIAL CELL PROLIFERATION AND ENTEROENDOCRINE CELL DIFFERENTIATION

Zhaoyi Peng*^1,2, Lingyu Bao¹, Bingyin Shi², Yunbo Shi¹

¹National Institutes of Health, USA,²Xi'an Jiaotong University School of Medicine, China

The adult intestinal epithelium has a high self‐renewal rate driven by intestinal stem cells (ISCs) in the crypts, which play central roles in maintaining intestinal integrity and homeostasis. Previous studies have suggested that thyroid hormone (T3) is essential for the development and/or maintenance of adult intestine. The genomic effects of T3 are mediated by thyroid hormone nuclear receptors (TRs), which are present in all vertebrates. Protein arginine methyltransferase 1(PRMT1), a TR coactivator, is highly expressed during intestinal maturation in vertebrates, including mouse and frog. However, its role in adult intestinal homeostasis remains unclear.

Here, we found that PRMT1 is highly expressed in the proliferating transit‐amplifying (TA) cells and ISCs of adult mouse intestinal crypts, but not in the villi, where most differentiated cells are located. By using tamoxifen‐induced intestinal epithelial cell‐specific deletion of PRMT1 in adult mice, we observed a significant decrease in global levels of asymmetrical dimethylation on arginine‐3 of histone H4 (H4R3me2a) in the crypts. Interestingly, the mutant mice exhibited elongated crypts in the small intestine along with an expanded population of TA cells. Additionally, inducible PRMT1 deletion led to increased cell death, which compensated for increased cell proliferation in the crypts to maintain overall intestinal morphology. Furthermore, transcriptional analyses revealed top 30 enriched upregulated pathways were all involved in enteroendocrine cell (EEC) function, as well as upregulation of EEC‐specific hormones and transcription factors in the PRMT1‐deficient small intestine. Concomitantly, the number of EEC and Neurogenin 3‐positive EEC progenitor cells dramatically increased in the mutant small intestine. Moreover, the downstream target genes of Neurogenin 3 (such as Neuod1, PAX4, PAX6, and Insm1) were upregulated in the mutant crypts.

Together, our results revealed that the loss of PRMT1 in the adult intestinal epithelium altered TA cell proliferation and EEC differentiation, which probably via enhancement of Neurogenin 3‐mediated commitment to the EEC lineage. Thus, our results provide potential roles of PRMT1 as an essential transcriptional regulator of EEC determination.

POSTER 269

Thyroid Cancer Basic Poster

THE PRESENCE OF PUNCTATE ECHOGENIC FOCI IN THYROID NODULES IS ASSOCIATED WITH CLDN1 AND TIMP1 OVEREXPRESSION

Anette Gastelum‐Quiroz*^1,2,3, Noemí García‐Magallanes², Andrea Ross‐Orozco^2,3, Eliakym Arámbula‐Meraz⁴, Fred Luque‐Ortega⁵, Sigfrido Miracle⁶, Marco Álvarez‐Arrazola⁷

¹Licenciatura en Ciencias Biomédicas, Unidad Regional Mazatlán, Universidad Autónoma de Occidente, Mexico,²Laboratorio de Biomedicina y Biología Molecular, Unidad Académica de Ingeniería en Biotecnología, Universidad Politécnica de Sinaloa, Mexico,³Posgrado en Ciencias Biomédicas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico,⁴Laboratorio de Genética y Biología Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico,⁵Laboratorio de Ciencias Básicas, Facultad de Odontología, Universidad Autónoma de Sinaloa, Mexico,⁶Centro de Investigación en Ciencias de la Salud, Universidad Anahuac, Mexico,⁷Álvarez & Arrazola Radiólogos, Mexico

Ultrasound is the preferred imaging method for assessing thyroid disease. This non‐invasive ionizing‐radiation free approach provides information about thyroid nodules, such as the presence of punctiform echogenic foci. This sonographic finding has high sensitivity and specificity for thyroid carcinoma diagnosis. Additionally, integrating this sonographic characteristic with molecular biomarkers, such as CLDN1 and TIMP1 genes expression, may provide excellent diagnostic value and support clinical‐surgical decision‐making. CLDN1 is a fundamental gene in the preservation of epithelial and endothelial junctions, as well as in the maintenance of the cytoskeleton and cell signaling. TIMP1 exhibits metalloproteinase inhibitory functions and has important physiological implications for processes such as cell growth, survival, apoptosis, cell proliferation and differentiation.

Objectives: The aim of this study was to analyze the expression of CLDN1 and TIMP1 genes in thyroid nodules and their association with the presence of punctiform echogenic foci.

Methods: CLDN1 and TIMP1 gene expressions were analyzed by RT‐qPCR in 42 thyroid nodules (malignant = 18, benign = 24). A radiologist with expertise in thyroid pathology obtained the ultrasound images with a Siemens Antares ultrasound machine with a high‐frequency linear transducer.

Results: 42 samples of thyroid nodules were analyzed, 41 of which belonged to female patients and 1 to a male patient. The patients' average age was 48.94 ± 2.273. CLDN1 was found to be expressed 3.68 ± 0.759 times (p = 0.02, N = 42), and TIMP1 was found to be expressed 1.77 ± 0.422 times in nodules with punctate echogenic foci (p = 0.042).

Conclusion: These findings suggest an association between CLDN1 and TIMP1 overexpression and the presence of punctiform echogenic foci in thyroid nodules. The study of biomarkers in thyroid nodules represents and active area of research, and the identification of associations between biomarkers and sonographic findings suggestive of malignancy could contribute to better precision in thyroid nodule management.

POSTER 270

Thyroid Cancer Basic Poster

UPREGULATION OF CLDN1 IN THYROID NODULES AND ITS ASSOCIATION WITH BRAF V600E MUTATION

Andrea Ross‐Orozco*^1,2, Eliakym Arámbula‐Meraz³, Anette Gastelum‐Quiroz^4,2,5, Fred Luque‐Ortega⁶, Marco Álvarez‐Arrazola⁷, Noemí García‐Magallanes²

¹Posgrado en Ciencias Biomédicas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico,²Laboratorio de Biomedicina y Biología Molecular, Unidad Académica de Ingeniería en Biotecnología, Universidad Politécnica de Sinaloa, Mexico,³Laboratorio de Genética y Biología Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico,⁴Posgrado en Ciencias Biomédicas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Mexico,⁵Licenciatura en Ciencias Biomédicas, Unidad Regional Mazatlán, Universidad Autónoma de Occidente, Mexico,⁶Laboratorio de Ciencias Básicas, Facultad de Odontología, Universidad Autónoma de Sinaloa, Mexico,⁷Álvarez & Arrazola Radiólogos, Mexico

Thyroid carcinoma is the most prevalent endocrine neoplasm. The most recurrent mutation in thyroid cancer (TC) is the V600E substitution in BRAF, which induces the over‐activation of the MAPK pathway. The interaction between this pathway and the deregulation of genes that facilitate tumorigenesis such as CLDN1 could be useful for decision‐making related to surgical removal and the degree of initial resection; however, there is a lack of information on the association of CLDN1 expression with BRAF V600E.

Objective: Evaluate the gene expression of CLDN1 in BRAF‐mutated and BRAF‐unmutated thyroid nodules.

Methods: RT‐qPCR was performed to assess BRAF genotyping (rs113488022) and CLDN1 expression in 94 thyroid nodule biopsy samples (TC = 48). Clinicopathological data was retrieved to establish further associations.

Results: Mutated BRAF thyroid nodules were found to be 7.14 ± 0.293 times more expressed than those without the mutation (p < 0.001, N = 94). BRAF V600E mutation was identified in patients with TC exclusively. CLDN1 expression was 41.315 ± 0.554 times greater in patients with TC than in those without TC (p < 0.001). Heterozygous patients had a change factor of 6.8, whereas mutated homozygotes had a change factor of 7.5 (p < 0.001, N = 94). CLDN1 mean expression is significantly higher in A allele carriers compared to normal homozygotes (p < 0.001). When analyzing just within the TC group, the behavior is maintained, suggesting a potential association between the mutated allele and the expression of these genes.

Conclusion: CLDN1 is significantly upregulated in TC patients carrying the BRAF V600E mutation. BRAF V600E is only observed in patients with TC, implying a biological connection between them, which can be explained via MAPK; subsequent studies are needed to confirm the correlations.

POSTER 271

Iodine Uptake and Metabolism Basic Poster

THYROGLOBULIN SUPPRESSES THE EXPRESSION AND LOCALIZATION OF THE NOVEL IODIDE TRANSPORTER SLC26A7 IN RAT THYROID FRTL‐5 CELLS AND HUMAN THYROID FOLLICULAR CELLS

Mitsuo Kiriya*¹, Akira Kawashima¹, Yoko Fujiwara¹, Yuta Tanimura¹, Aya Yoshihara², Yasuhiro Nakamura³, Kazunari Tanigawa⁴, Koichi Suzuki¹

¹Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Japan,²Department of Internal Medicine, Showa University Northern Yokohama Hospital, Japan,³Center for Promotion of Pharmaceutical Education & Research, Faculty of Pharma‐Science, Teikyo University, Japan,⁴Department of Molecular Pharmaceutics, Faculty of Pharma‐Science, Teikyo University, Japan

[Objective] Recently, solute carrier family 26 member 7 (SLC26A7), a novel apical iodide transporter of thyrocytes, was identified as the responsible gene for congenital hypothyroidism. However, the underlying mechanisms that regulate the expression of SLC26A7 remain unclear. We investigated the effect of follicular thyroglobulin (Tg), a potent autoregulator of thyroid‐specific gene expression, on the expression and localization of SLC26A7 in rat thyroid FRTL‐5 cells and primary culture of human thyrocytes.

[Methods] Suspension culture of human thyroid follicles were prepared from thyroid tissues obtained at surgery. FRTL‐5 cells and suspension culture of human thyroid follicles were stimulated by follicular concentrations of Tg. SLC26A7 mRNA and protein expression levels were evaluated using real‐time PCR and Western blotting, respectively. The human SLC26A7 promoter was cloned, and its activity was evaluated by luciferase reporter gene assay. Subcellular localization of SLC26A7 in FRTL‐5 cells and rat thyroid tissue sections were analyzed using confocal laser scanning microscopy.

[Results] Follicular concentration of Tg suppressed the promoter activity, mRNA expression and protein levels of SLC26A7 in FRTL‐5 cells. Tg also suppressed SLC26A7 mRNA levels of human thyroid follicles obtained from normal and Graves' disease, but thyroid goiters escaped from the effect of Tg. Furthermore, Tg inhibited the ability of TSH to induce the plasma membrane localization of SLC26A7. In rat thyroid sections, SLC26A7 was strongly expressed on the apical membrane where Tg accumulation was poor, whereas it was barely observed where Tg accumulation was abundant.

[Conclusion] We have demonstrated in FRTL‐5 and suspension culture of normal human thyroid follicles that follicular Tg suppressed the expression of the novel iodide transporter SLC26A7. We have previously reported that TSH translocated SLC26A7 from perinuclear area to the cell membrane where it functions as a transporter. On the other hands, Tg inhibited the action of TSH to localize SLC26A7 to the plasma membrane. These results corroborate our hypothesis that the function of individual follicles is strongly regulated by the level of Tg accumulated in the follicular lumen.

POSTER 272

Autoimmunity Translational Poster

ROLE OF CONFORMATIONAL STATES OF THE CD40 RECEPTOR IN ITS ACTIVATION BY CD40 LIGAND: IMPLICATIONS FOR THYROID AUTOIMMUNITY

Aizhan Kozhakhmetova*¹, Roman Osman², Yaron Tomer¹

¹Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, USA,²Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, USA

Objective: CD40, a cell surface receptor expressed on APCs, plays a key role in Graves' disease pathoetiology. We have shown that activation by CD40L leads to CD40 signaling through NF‐kB resulting in inflammation in thyroid cells [Lee JCEM 2017]. CD40 consists of extracellular (ED), transmembrane, and intracellular domains. The ED of CD40 has two flexible cysteine‐rich domains CRD1/CRD2 and CRD3/CRD4, which interact with CD40L [Naismith Structure, 1996]. The role of conformational changes in CRD is not fully understood. Structural analysis and molecular dynamics (MD) simulations suggest that the CRD can exist in two conformations: closed (CC) and open (OC), with only OC leading to the assembly of an active complex. The role of conformational properties in activation mechanisms of CD40, was investigated in in vitro studies using CD40 effector cells and small molecules (SMs) targeting either OC (SM1) or CC (SM2) of the CRD.

Methods: We utilized CD40 cells expressing CD40 and NF‐kB reporter gene (R&D Systems). Recombinant hCD40L was used to activate CD40 on the cells, and a hCD40 monoclonal antibody as a control for blocking CD40 activation. CD40 cells were plated with addition of serial dilutions of SM1 or SM2. CD40L (4ug/ml) was added, and cells were incubated for 6h at 37°C. Luminescence was quantified using BMG FLUOstar plate reader. Percent activation of cells was estimated [corrRLU SM/corrRLU CD40L]*100%, where corrRLU is the relative luminescence corrected for background. MD simulations were conducted with AMBER and docking with the Glide program (Schrodinger).

Results: Our findings showed that SM1, obtained from docking in OC enhanced activation of CD40 cells with CD40L, whereas SM2, obtained from docking in CC inhibited activation. Both exerted their effect in a dose‐dependent manner.

Discussion/Conclusion: Our results suggest that conformation of CD40 ED is critical for its activation by CD40L. The OC is required for signaling. In contrast, CC stabilized by SM2 does not signal and shows inhibition of signaling. Since CD40 activation on thyroid cells can trigger thyroid autoimmunity these results may aid in the development of targeted therapeutics for Graves' disease.

POSTER 273

Thyroid Cancer Translational Poster

EXPLOITING ENDOCYTIC FACTORS AS DRUGGABLE TARGETS TO ENHANCE SODIUM IODIDE SYMPORTER ACTIVITY WITH CLINICAL IMPLICATIONS FOR RADIOIODIDE THERAPY

Katie Brookes¹, Ling Zha¹, Jana Kim², Merve Kocbiyik¹, Selvambigai Manivannan¹, Kavitha Sunassee², Philip Blower², Hannah Nieto¹, Vicki Smith¹, Martin Read¹, Christopher McCabe*¹

¹Institute of Metabolism and Systems Research, University of Birmingham, United Kingdom,²School of Biomedical Engineering & Imaging Sciences, King's College London, United Kingdom

Objective: Suboptimal radioiodide (RAI) treatment is frequently associated with diminished targeting and retention of the sodium iodide symporter (NIS) at the plasma membrane (PM). The mechanisms which govern the endocytosis of NIS away from the PM are however ill‐defined and may have therapeutic potential. We recently demonstrated that NIS internalisation was modulated by the interaction of a C‐terminal diacidic motif with the heterotetramer Adaptor Protein 2 (AP2) – a key regulatory factor in endocytosis. Here, we determined whether NIS endocytosis represents a druggable process to enhance RAI uptake.

Methods: PM localisation of NIS was quantified via NanoBRET and cell surface biotinylation assays (CSBA). RAI (¹²⁵I) uptake assays were used to monitor NIS function in vitro. Intravenous technetium‐99m pertechnetate (^99mTc) uptake was used to evaluate NIS function in wild‐type BALB/c mice.

Results: The drug chloroquine (CQ) rapidly increased ¹²⁵I uptake in TPC1‐NIS (2.54‐fold; P < 0.0001) and 8505C‐NIS (1.93‐fold; P < 0.05) cells peaking after 8 hr, which was abrogated by co‐treatment with the endocytosis inhibitor Dynasore. Subsequent CSBA confirmed elevated levels of cell‐surface NIS in CQ‐treated thyroid cancer cells. This finding was supported in live CQ‐treated cells via KRAS‐NanoBRET assays, where CQ gave a strong BRET signal similar to Dynasore, suggesting that NIS was retained at the PM. To challenge this, we ablated PICALM, an endocytic factor known to recruit AP2/clathrin to the PM which prevented significant induction of RAI uptake by CQ. In vivo, CQ treatment of BALB/c mice significantly enhanced thyroidal ^99mTc‐uptake in combination with the HDACi SAHA (52.7%; n = 10; P = 0.0003), as well as increasing thyroidal expression of NIS (2.2‐fold; P < 0.0001), TSHR (1.9‐fold; P = 0.001) and PAX8 mRNA (1.6‐fold; P = 0.003).

Conclusion: Our findings suggest that CQ interferes with the PICALM/AP2/clathrin machinery which controls NIS endocytosis, identifying it as an FDA‐approved pharmaceutical agent which alters NIS endocytosis, with translatable potential to improve radioiodide therapy.

POSTER 274

Thyroid Cancer Translational Poster

SINGLE‐CELL RNA SEQUENCING REVEALS THE IMMUNE MICROENVIRONMENT OF ATC

Zhenghao Wu*, Peng Zheng

Union Hospital, Huazhong University of Science and Technology, China

Objective: To analyze the immune microenvironment of thyroid cancer and explore potential immunotherapy targets for anaplastic thyroid cancer (ATC).

Methods: Multiple single‐cell RNA sequencing datasets of thyroid tissues, including normal thyroid, PTC, and ATC, were integrated. Patients with Hashimoto's thyroiditis were excluded, and immune cells of all patients were subjected to clustering analysis.

Results: Compared to other thyroid lesions, T cells and myeloid cells were significantly increased in ATC. T cell cluster 5 was enriched in PTC, indicating a memory state of CD8+ T cells. T cells (cluster 2 and 6) were specifically enriched in ATC and found to have highly activated, differentiated, and proliferative functions, producing IFN I, IL2, IL4, IL6, IL12, and TNF, as well as responding to IL‐4 and IL‐12. This suggests high proliferation and killing capacity of CD8+ T cells. T cells (cluster 2 and 6) also highly expressed immune checkpoints, including LAG3 and TIM3 (HAVCR2), while PD‐1 expression was low.

Conclusion: Immunotherapy targeting LAG3 and TIM3 checkpoints may be more effective for ATC.

POSTER 275

Disorders of Thyroid Function Case Study Poster

CONVERSION TO GRAVE'S DISEASE FROM HASHIMOTO'S THYROIDITIS ‐ A RARE PHENOMENON!

Qasim Iqbal*, Sakshi Sharma, Karina Romo, Jared Dendy

Ochsner Clinic Foundation, USA

Background: Chronic lymphocytic thyroiditis, known as Hashimoto's thyroiditis, is an autoimmune disorder and the leading cause of hypothyroidism in iodine‐sufficient areas. Conversely, Graves' disease, while also an autoimmune disorder, is the leading cause of hyperthyroidism. In Hashimoto's thyroiditis, thyroid follicular destruction is mediated by autoimmune apoptosis and lymphocytic infiltration leading to progressive thyroid fibrosis; while in Graves' disease, the thyroid‐stimulating immunoglobulins (TSIs) bind and activate TSH leading to thyroid hypertrophy and increased thyroid hormone synthesis within thyroid follicles. Few cases have been reported of conversion from Hashimoto's thyroiditis to Graves' disease–the following presents a case of a woman with such conversion.

Clinical Case: 72‐year‐old‐woman with Hashimoto's Thyroiditis (TPO Ab 535.5 IU/ml (nl <6 IU/ml)) for more than 5 years, Cerebrovascular disease, Systemic Lupus Erythematosus, and Breast cancer (HER2+ DCIS on Trastuzumab) presented to the endocrine clinic for evaluation of suppressed TSH. Over the past year, her levothyroxine dose was tapered from 100 mcg daily to 25 mcg daily, and eventually discontinued in June 2022 when she became hyperthyroid with a TSH of 0.097 uIU/ml (nl 0.4‐4.0 uIU/ml) and clinical manifestations of unintentional 12 lbs weight loss in 2 months, palpitations, and hair loss. She started carvedilol 12.5 mg twice daily with some symptomatic improvement. Her course was complicated by a viral URI after a chemotherapy infusion in October 2022. Her symptoms of congestion and rhinorrhea resolved with conservative management, however, her TFTs showed lowered TSH of 0.021 uIU/ml. NM scan showed mildly elevated 24‐hour thyroid uptake of 30.6% (nl 10‐30%). The examination noted tachycardia and resting tremor, without thyromegaly, thyroid tenderness, exophthalmos, or myxedema. Labs revealed TSI of 8.06 iu/l (nl <0.10 iu/l), TSH of 0.010 uIU/ml, and fT4 at 1.61 ng/dl (nl 0.71‐1.51 ng/dl). Given her elevated TSI, hyperthyroid symptoms, and biochemical hyperthyroidism, she was started on methimazole 5 mg daily for the conversion of Hashimoto's thyroiditis to Graves' disease with planned repeat TFTs in 6 weeks.

Conclusion: Conversion between Hashimoto's thyroiditis to Graves' disease is rare and its etiology is not yet understood. Immunomodulation from monoclonal antibodies or an injury from a viral infection causing an inflated response producing TSIs are two hypothesized factors leading to the conversion from Hashimoto's to Graves'. Improved reporting of these cases could lead to a better understanding of factors contributing to this rare phenomenon.

POSTER 276

Disorders of Thyroid Function Case Study Poster

AN UNUSUAL CASE OF POST‐PARTUM HYPERTHYROIDISM

Samarth Virmani*, Shalini Koshy, Faiza Mubeen, Jawairia Shakil, Bhargavi Patham, Monisha Singh, Trisha Cubb

Houston Methodist Hospital, USA

Introduction: Gestational trophoblastic disease (GTD) is characterized by abnormal proliferation of trophoblastic cells and excess secretion of human chorionic gonadotrophin (hCG). Choriocarcinoma is a malignant form of GTD. hCG and TSH are structurally similar glycoproteins as they share identical alpha subunits and have highly homologous beta subunits. Thus, at increased levels, hCG can cross react with TSH receptors which can lead to hyperthyroidism due to competitive binding of beta‐hCG to TSH receptors. We present a case of symptomatic post‐partum hyperthyroidism that unveiled a diagnosis of metastatic choriocarcinoma.

Case Presentation: A 27yo G1P1 female presented to the emergency room 5 weeks post‐partum with a 4‐week history of vaginal bleeding, palpitations and tremulousness. Of note, she delivered via cesarean section at 27 weeks gestation due to severe fetal growth restriction and non‐reassuring fetal status. Admission vitals were significant for heart rate of 117 bpm and temperature of 99.1 F. Labs revealed hyperthyroidism with TSH <0.01 uIU/mL (0.27‐4.20 uIu/mL), free T4 > 5.2 ng/dL (0.9‐1.7 ng/dL) and total T3 476 ng/dL (80‐200ng/dL). TSI and TPO antibodies were negative. Hyperthyroidism treatment was initiated with beta blocker, methimazole and cholestyramine. Ultrasound showed heterogenous and hypervascular thyroid without nodularity. Given the time frame, there was initial concern for post‐partum thyroiditis, but workup revealed elevated serum hCG of 714,131mIU/mL (0‐5 mIU/mL). CT chest/abdomen/pelvis showed a 6 cm uterine lesion and bilateral pulmonary nodules. Metastatic choriocarcinoma was confirmed via lung nodule biopsy. Given high risk disease, she was placed on induction chemotherapy with cisplatin and etoposide followed by EMA/CO (etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine). Subsequently, hCG rapidly decreased, and hyperthyroidism improved allowing de‐escalation of methimazole and cessation of cholestyramine and beta blocker. Approximately 4 months since diagnosis, hCG is <1 mIU/mL and she remains euthyroid off methimazole.

Discussion: Our case demonstrates the importance of consideration of GTD as a cause of hyperthyroidism particularly in the post‐partum setting. Due to the cross reactivity, patients with hCG >50,000 mIU/mL should have assessment of thyroid. It is crucial for clinicians to recognize hyperthyroidism in the setting of GTD to facilitate prompt care and prevent complications of thyrotoxicosis.

POSTER 277

Disorders of Thyroid Function Case Study Poster

EXTRACORPOREAL MEMBRANE OXYGENATION AND THYROID HORMONE LEVELS IN CYSTIC FIBROSIS: A CASE SERIES

Maria Pesantez*¹, CARLOS PEREZ², SILVIA GRA¹

¹UNIVERSITY OF MIAMI, USA,²Rutgers Health/Trinitas Regional Medical Center, USA

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass life support where hemoglobin is fully saturated with oxygen. Critical illness can alter thyroid hormonal axis and metabolism as seen in Non thyroidal Illness(NTI).

While on ECMO, free T3 levels could decrease due to an activation of inflammatory mediators, hypothermia and hemodilution that results in a shorter half‐life of T3.

Given the T3 positive inotropic and vasodilator effects, it could be administered to enhance the cardiac output and overall hemodynamics. However, the impact on overall mortality is unclear.

There are only a handful of publications on the thyroid function test(TFT) variations while on ECMO. Our aim is to discuss the changes observed in patients with Cystic Fibrosis(CF)

Case1

A 37‐year‐old female with CF was admitted for acute respiratory failure requiring ECMO. She was diagnosed with a right 0.3 cm papillary thyroid carcinoma 3 years prior. Pathology reported clear margins but lymph node involvement, stage T1aN1b. Patient underwent total thyroidectomy and radical lymph node dissection followed by radioactive Iodine therapy. She was compliant with levothyroxine and had an excellent biochemical and structural response. Her last Thyroglobulin and TSH were <0.1 and 1.1 respectively. On admission TSH was 87.9 and FT4,0.76. Levothyroxine 120mcg IV was started. Seventeen days after the admission, TSH was 66.630 and FT4:>7.77. Repeated Testing in 24 hours showed: TSH63.550 and ft4:1.12. Levothyroxine was continued at the same dose, unfortunately the patient expired.

Case2

A 28 year‐old female with CF was transferred from another country for acute hypoxic respiratory failure requiring ECMO. Bradycardia on arrival prompted the team to obtain a TFT that showed:TSH0.094,ft4:0.54 and t3:31. No prior TSH was available. Repeated laboratories on day 6 showed:TSH1.390, FT4:1.25, rT3:28. Levothyroxine started on admission was stopped as abnormalities were attributed to NTI.

Discussion: In both cases, thyroid abnormalities were initially attributed to NTI. Management was challenging due to the unpredictable fluctuations in TFT.

A study in neonates showed that only one hour after starting ECMO, TT4 and TSH declined(P < 0.05). However, in the next 12 hours, TSH increased. Therefore, thyroxine supplementation was not recommended as the increase in TSH is expected.

There are other factors that could interfere with TFT in patients with CF including nutrition deficiencies. However, there is limited data on the effect of ECMO on thyroid hormones and LT4/T3 supplementation.

POSTER 278

Thyroid Cancer Case Study Poster

ECTOPIC CUSHING'S SYNDROME SECONDARY TO MEDULLARY THYROID CANCER: A CASE REPORT AND DISCUSSION OF TARGETED THERAPIES

Aria Jazdarehee*¹, Jennifer Jacquier^1,2, Omar Abdel‐Rahman^1,2

¹University of Alberta, Canada,²Cross Cancer Institute, Canada

Introduction: Medullary thyroid cancer (MTC) is a neuroendocrine tumor associated with activating mutations of the rearranged during transfection (RET) proto‐oncogene. In rare cases, these tumors may secrete adrenocorticotropic hormone or corticotropin‐releasing hormone, resulting in a paraneoplastic ectopic Cushing's syndrome (ECS). Paraneoplastic ECS carries a high risk of mortality if it is not promptly recognized and treated, however management has remained difficult due to its lack of response to anti‐adrenal therapies.

Case Description: A 37‐year‐old male was diagnosed with metastatic MTC involving cervical and superior mediastinal lymph nodes, liver, and spleen. On presentation, he reported symptoms of cortisol excess and laboratory testing was in keeping with ECS. Genetic testing was negative for germline RET mutation and somatic testing was positive for somatic RET mutation (RET_ [p.M918T; c.2753T>C], variant allele frequency 15.6%). He began treatment with vandetanib, a multityrosine kinase inhibitor, which resulted in decreased tumor burden as well as clinical and biochemical resolution of ECS. Due to progressive structural disease 10 months later, he was switched to the selective RET inhibitor selpercatinib, which was followed by a rapid reduction of cortisol nearing the threshold of adrenal insufficiency. Tumor markers were also improved, and repeat imaging is pending.

Discussion: In summary, our case highlights the efficacy of tyrosine kinase inhibitors in the management of ECS secondary to MTC. Selective RET inhibitors may emerge as preferred targeted treatment options due to better efficacy and toxicity profiles compared to multikinase inhibitors. Clinicians should monitor for adrenal insufficiency following treatment of paraneoplastic ECS with selective RET inhibitors.

POSTER 279

Thyroid Cancer Case Study Poster

PAPILLARY THYROID CANCERS WITH NTRK FUSION MUTATIONS: BENIGN CYTOLOGIC APPEARANCE AND CLINICALLY AGGRESSIVE DISEASE

Sapir Nachum*, Ana Rivadeneira, Zubair Baloch, D Farwell, Susan Mandel

Perelman School of Medicine, University of Pennsylvania, USA

Introduction: Thyroid nodule sonographic features and fine needle aspiration (FNA) cytology guide our utilization of molecular testing. We present a patient in whom ultrasound and FNA cytology suggested a benign lesion, but further molecular testing showed NTRK fusion mutation raising concern for malignancy.

Case Presentation: 50 year old man who was found to have enlarged thyroid on physical exam. Ultrasound was notable for multiple isoechoic left thyroid nodules (TR2) and soft tissue lesions in the left lateral neck with sonographic characteristics of normal thyroid. FNA cytology of a left lateral neck soft tissue mass showed benign appearing follicular cells potentially consistent with ectopic thyroid. Thyroseq v3 was sent due to clinical concern given the presence of multiple lateral masses and was positive for ETV6/NTRK3 fusion mutation. He proceeded with total thyroidectomy and central and left lateral neck dissection. Surgical pathology showed multifocal papillary thyroid cancer with predominantly macrofollicular variant and focal papillary solid and clear cell patterns with angioinvasion and metastases to central and lateral neck lymph nodes. CT chest notable for fewer than 10 scattered 2‐3 mm pulmonary nodules, thought to be indeterminate. He was treated with 100mCi I‐131 remnant ablation and the post therapy scan demonstrated uptake in the thyroid bed, central neck and left lateral neck. Pulmonary uptake was not present.

Discussion: Thyroid nodules with NTRK fusion mutations may have a benign or indeterminate appearance on cytology due to subtle nuclear features. Despite benign appearing cytology, lesions with these mutations have a probability of papillary thyroid cancer approaching 100%. Although rare, NTRK fusion mutations are now recognized in 5‐6% of adults with PTC. Tumors with this mutation had a high likelihood of multifocality, extrathyroidal extension, vascular invasion, lymph node metastases, and distant metastases.

POSTER 280

Thyroid Cancer Case Study Poster

THYROID ABLATION FOR LARGE BRAF/TERT POSITIVE THYROID CANCER AND IMPROVEMENT FOUR YEARS AFTER THE FIRST TREATMENT

Niketa Kalara*, Crystal Acosta, Agustin Andrade

Mount Sinai Medical Center, USA

Surgery is the standard treatment for thyroid cancer. New approaches, including active surveillance and thyroid ablation, have been described for microscopic thyroid cancer. Herein we describe a 5.9cm thyroid cancer in a patient deemed inoperable due to a cardiovascular condition.

A 92‐year‐old female presented in 2018 with a 5‐year history of a right thyroid nodule with a 4/4 cosmetic score and positive Pemberton's sign. TSH was 1.9 mIU/L (0.5‐5) on Levothyroxine 75 mcg/day, and she had a positive anti‐thyroid peroxidase antibody. Ultrasound detected a solid and heterogeneous nodule that measured 4.8x5.9cm (58mL) with a regular border and no lymphadenopathy. The left lobe had two solid, hypoechoic lesions measuring 1.9cm and 1.2cm. CT scan showed a 6.0 cm right heterogeneous lesion with tracheal deviation and mild tracheal stenosis. FNA (Right) Bethesda III with Positive TERT mutation. Due to significant atherosclerotic heart disease, she was deemed to be a poor surgical candidate and she declined surgery. In March 2019, radiofrequency ablation (RFA) was performed on the right nodule. In June 2019, the right nodule measured 3.8x3.1cm (22mL) showing a 62% reduction. In February 2022, the right nodule measured 3.2x5.3cm (29mL), a 24% increase from the nadir; no lymphadenopathy was present. FNA was repeated and this time it was Bethesda VI, positive for BRAF and TERT. One month later, percutaneous laser ablation (PLA) was performed, and 14503 joules were delivered without any complication. In February 2023, the right nodule measured 2.4x3.2x4.2cm (17.6mL) and CT showed right 2.6cm with mild tracheal deviation and no lymphadenopathy.

To the best of our knowledge, this is the first large thyroid cancer with adverse genetic mutations, BRAF and TERT, that due to co‐morbidity and refusal to surgery was treated with thyroid ablation; first with RFA and three years later with PLA. In the end, the patient is now 97 years old and satisfied with the decrease in the cosmetic score, now 2/4, and asymptomatic. Despite the genetic mutations, she has not developed metastatic lymphadenopathy on imaging. This case may open the door for more patients with thyroid cancer who cannot have surgery due to comorbidities.

POSTER 281

Thyroid Cancer Case Study Poster

ABNORMAL ULTRASOUND FEATURES AND CLINICAL MANIFESTATIONS OF THYROID METASTATIC CARCINOMA: A RARE CASE REPORT

Yuanyuan Li^1,2,3,4, Shuhang Xu*^1,2,3,4, Guofang Chen^1,2,3, Chao Liu^1,2,3, Wenbo Ding⁵, Ziyu Jiang⁶

¹Endocrine and Diabetes Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, China,²Jiangsu Province Academy of Traditional Chinese Medicine, China,³Key Laboratory of TCM Syndrome & Treatment of Yingbing of State Administration of Traditional Chinese Medicine, China,⁴Nanjing University of Chinese Medicine, China,⁵Ultrasound department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, China,⁶Oncology department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, China

Introduction: Metastases from nonthyroid malignancies to the thyroid gland have been reported in 1.4%–3% of patients who have thyroidectomy. Prognosis of thyroid metastatic carcinoma is usually poor. Therefore, we should pay attention to the awareness of thyroid metastatic carcinoma. Early discovery and treatment could prolong survival and improve quality of life.

Description of the Case: A 41‐year‐old woman came to our clinic because of “detected hypothyroidism for 1 day”. The patient reported fatigue and anterior neck pain. Two years ago, she had been diagnosed with squamous cell carcinoma of the cervical stage IVB, with left supraclavicular lymph node metastasis, for which she had received chemotherapy, radiotherapy, molecular targeted therapy and tumor immunotherapy (Camrelizumab, a PD‐1 inhibitor).

At our initial outpatient visit, thyroid function tests showed FT3 2.33pmol/l (3.10‐6.80), FT4 7.22pmol/l (12.00‐22.00), TSH 78.2uIU/ml (0.270‐4.200); US showed diffuse hypoechoic lesions of the thyroid gland. She was treated with levo‐thyroxine. However the symptoms had worsened. Meanwhile, the erythrocyte sedimentation rate and C‐reactive protein increased significantly. Considering that subacute thyroiditis cannot be ruled out, prednisone was tried used for treatment. At early, the symptoms of neck pain relieved, but the pain quickly recurred, and continued use of prednisone did not alleviate it. Subsequently, US‐guided core needle biopsy (CNB) of the right lobe of thyroid was performed. Histopathology results showed infiltrating or metastatic carcinoma and immunohistochemistry confirmed squamous cell carcinoma. Therefore, the patient suffered from thyroid metastases from the original cervical carcinoma. Afterwards, she admitted in the oncology department, received routine expectant and supportive therapies such as maintaining electrolyte balance, parenteral nutrition, anti‐inflammation. Since she was in the end stage of malignant tumor, the disease progressed rapidly and the prognosis was poor.

Discussion: For tumor patients who use immune checkpoint inhibitors (ICI), when experiencing abnormal thyroid function or thyroid ultrasound morphology, endocrine immune‐related adverse events of ICIs are often the first consideration, however it is also necessary to be wary of distant metastasis of tumors to the thyroid gland.

POSTER 282

Thyroid Cancer Case Study Poster

TREATMENT OF LOCALLY AGGRESSIVE V600 E MUTATED DIFFERENTIATED PAPILLARY THYROID CANCER WITH DABRAFENIB AND TRAMETINIB

Layal Esper*¹, Neha Bapat², Arjun Joshi¹, Chelsea Baldwin¹

¹George Washington University, USA,²Greater Baltimore Medical Center, USA

Introduction: Papillary thyroid carcinoma (PTC) is the most common histological type of differentiated cancer of the thyroid gland (1). PTC is typically an indolent tumor with a 10‐year survival of 93% (2). Total or near‐total thyroidectomy‐remains the standard of care for PTC over one centimeter. A subset of aggressive differentiated thyroid tumors exhibits extrathyroidal extension leading to a tumor which may be unresectable due to the morbidity of surgical intervention (3).

Case: 66‐year‐old woman with PMHx of HTN who presented for hoarseness of her voice and was found to have a neck mass complicated by right recurrent laryngeal nerve paralysis and tracheal invasion. The patient was recommended for urgent surgical debulking but preferred to wait six weeks. Prior to surgery date, the patient presented with hemoptysis precipitating acute respiratory failure that required emergent intubation and tracheostomy placement.

The patient was taken to the operating room the following day and bilateral neck dissection was performed followed by attempted thyroidectomy which was aborted due to invasion of the right carotid artery, right trachea, and prevertebral fascia. FDG PET scan obtained after attempted resection, showed 4.2 cm hypermetabolic mass within the left lobe. Molecular analysis of lymph nodes showed BRAF V600E mutation.

Patient was started on Dabrafenib 150mg BID and trametinib 2mg daily neo‐adjuvant therapy for unresectable T4N1b differentiated papillary thyroid cancer with treatment goal of local tumor control and if tumor volume reduction reassessment for possible surgical candidacy without significant morbidity.

After two months of targeted therapy the patient had improvement in her ability to phonate. FDG PET CT scan after 3 months demonstrated complete resolution of FDG avidity and tumor reduction. Thyroglobulin decrease from 1197.2ng/nl pretreatment to 13.4 ng/ml.

Discussion: We present the case of a locally aggressive unresectable differentiated BRAFv600E mutated papillary thyroid cancer that responded to neoadjuvant dabrafenib and trametinib regimen over the course of 3 months as evidenced on FDG PET CT scan and decreasing thyroglobulin levels, now improving her surgical candidacy. Current literature on neoadjuvant therapy in differentiated thyroid cancer is limited to tyrosine kinase inhibitor therapy, however risk of bleeding is concerning in patients with known life‐threatening hemoptysis (4). Wang et al (5) had reported a case series of treatment of 6 patients with BRAFV600E mutated anaplastic thyroid cancer with complete surgical resection. To our knowledge this is the first case of targeted neoadjuvant therapy in a patient with differentiated BRAFV600E mutated papillary thyroid cancer.

POSTER 283

Thyroid Cancer Case Study Poster

ATYPICAL PRESENTATION OF CUTANEOUS METASTASIS IN PAPILLARY THYROID CANCER WITH TERT MUTATION

Panadeekarn Panjawatanan*, Meredith Sorensen, Jason Pettus, Dorothea Barton, Andrew Crawford

Dartmouth Hitchcock Medical Center, USA

Introduction: Regional lymph node metastasis accounts for 40% of papillary thyroid cancer metastatic cases. Distant metastasis to the lung, bone, liver, or brain can be found in up to 4%. However, cutaneous metastasis is rarely seen.

Case Description: A 67‐year‐old male with a history of chronic lymphocytic leukemia (CLL) presented with a right dominant thyroid nodule. A PET‐CT for CLL evaluation showed FDG avidity in the nodule. Ultrasound revealed a multinodular goiter with the largest thyroid nodule measuring 1.5 x 0.9 x 1.3 cm at the right upper pole, classified as TI‐RADS 5. FNA of that nodule showed a follicular neoplasm (Bethesda category IV). ThyGenX molecular testing revealed point mutations in KRAS (Q61R) and TERT promoter (C228T) genes with positive microRNA classifiers. He underwent a total thyroidectomy with limited central neck lymph node sampling. Pathology revealed a capsular invasive follicular variant papillary thyroid cancer with negative margins and no lymphovascular invasion nor lymph node metastases. He declined postoperative radioactive iodine and had an ATA excellent response to therapy at two months. Three years later, the patient noticed a 1 cm firm mobile mid‐anterior neck nodule adjacent to a prior surgical scar. Thyroglobulin was 1.1 ng/ml (<54.9 ng/ml) with an undetectable thyroglobulin antibody (<20 IU/ml). TSH values were all within 0.2 mcIU/ml during this period. FNA of the nodule was positive for papillary thyroid cancer. He underwent a local excision of the mass, and pathology revealed papillary thyroid carcinoma invasive of dermis and skeletal muscle with lymphovascular invasion. He received post‐operative 120 mCi of I‐131 ablation with uptake only in thyroid remnants. His thyroglobulin dropped to 0.6 ng/ml. The patient had negative CT neck and chest postoperatively.

Discussion: Cutaneous metastasis occurs in less than 1% of papillary thyroid cancer patients. The mechanism is still unknown, but possibilities include hematogenous or lymphatic spread, direct extension, or needle implantation during a biopsy. To our knowledge, this is the third case reported. The case we describe emphasizes the importance of considering unusual locations for metastatic disease, especially in patients with evidence of rising thyroglobulin or genomic findings with increased risk for aggressive behavior.

POSTER 284

Thyroid Cancer Case Study Poster

COWDEN SYNDROME; A CASE OF FOLLICULAR THYROID CARCINOMA DIAGNOSED IN THE PRESENCE OF PTEN MUTATION

Ashen Fernando*, Fazeena Shanaz

Geisinger Medical Center, USA

Introduction: Cowden syndrome (CS) is a rare autosomal dominant disorder associated with mutations in the phosphatase and tensin homolog (PTEN) gene. CS is a part of PTEN hamartoma tumor syndromes (PHTS) and is often an overlooked syndrome which predisposes to developing hamartomatous growths and increases risk for breast, thyroid, renal, endometrial and colorectal cancer. We present a case of follicular thyroid carcinoma diagnosed in an elderly patient who was incidentally found to have a PTEN variant.

Case :A 60‐year‐old male was found to have a pathogenic variant of PTEN c.277 C > G via “MyCode” genetic testing (voluntary population genetic screening). He underwent a screening colonoscopy which showed extensive polyp burden throughout the rectum and left colon. He was confirmed to have invasive adenocarcinoma of the colon and underwent a laparoscopic total abdominal colectomy with ileorectal anastomosis. A follow up PET‐CT scan showed incidental thyromegaly. Subsequently, he had a thyroid ultrasound showing multinodular goiter with one calcified nodule measuring 4.1 x 3.0 x 3.9 cm in the right lobe. Fine needle aspiration of this nodule showed benign follicular epithelial cells and colloid. He was monitored with serial neck ultrasounds which showed increasing glandular mass, however the patient remained without any symptoms of airway obstruction. A CT neck showed enlarged thyroid goiter with mass effect on the trachea. He underwent a staged thyroidectomy which showed 2.5 cm follicular carcinoma with transcapsular invasion into surrounding thyroid and 0.6 cm papillary microcarcinoma on the right. Thyrogen stimulated I‐131remnant ablation demonstrated remnant thyroid tissue with no evidence of metastatic disease. He is currently being closely monitored with a goal TSH <0.1.

Discussion: CS confers an up to 35% increased risk of developing follicular and papillary thyroid cancer, and a 75% risk of multinodular goiter, adenomatous nodules and follicular adenomas. Although the exact prevalence of CS is unknown, it is estimated to be around 1 in 200,000. Cancer surveillance is a crucial aspect in early detection of these tumors and has been shown to lead to better outcomes. The age of onset of thyroid cancer is unclear but yearly thyroid ultrasound is recommended as early as 18 years.

POSTER 285

Health Disparities Health Equity Clinical Poster

SOCIAL EXPOSOME AND THE TIP OF THE ICEBERG IN DIAGNOSING THYROID CANCER IN DISPROPORTIONATELY AFFECTED COMMUNITIES: A US POPULATION BASED STUDY

Isabel Riccio*¹, Jonathan Staav¹, Mohamed Hussein¹, Tessa Lavorgna¹, Peter Issa², Eman Toraih¹, Emad Kandil¹

¹Tulane University School of Medicine, USA,²Lousiana State University Health Sciences Center, USA

Objective: Social exposome is the integration of environmental exposures and socioeconomic status associated with cancer‐related health outcomes. Currently, there is no framework accounting for the comprehensive exposomic signature that may predict thyroid cancer (TC) related outcomes. We aim to identify geospatial exposome interactions to assess social and environmental exposures related to TC patients' outcomes.

Methods: Population‐based data from Surveillance, Epidemiology, and End Results (SEER) registries were analyzed to assess the contemporary burden of TC by age, gender, race/ethnicity, and pathological status. Social and environmental risk factors were evaluated across the country in correlation with TC rates.

Results: The age‐adjusted TC incidence rate was 15.5 per 100,000 and was higher in younger adults (27.3/100,000), females (22.8/100,000), and whites (16.9/100,000). Higher TC rates were among groups living in metropolitan counties compared to non‐metropolitan areas (p < 0.001). Individuals with higher incomes showed a 10.9% increase rate than those below $35,000 annual income. Interestingly, American Indian/Alaska Natives had a lower incidence rate (9.6/100,000), however presented more advanced stages at diagnosis (30.6%). Black individuals showed the least incidence rate (9.4/100,00), but the lowest 5‐year survival (88.2%). Further assessing socioeconomic markers, average annual counts of TC cases across counties was directly correlated with crowding (more than one household per room) (r = 0.37, p = 0.007), non‐English language (r = 0.67, p < 0.001), and poor education (less than grade 9) (r = 0.65, p < 0.001). Smoking cessation (r = ‐0.32, p = 0.001), fruit consumption (r = ‐0.36, p = 0.005), and residential UV exposure (r = ‐0.3, p = 0.027) were associated with lower TC rates.

Discussion: Incidence rates increased in higher‐income patients due to early screening. However, advanced disease risk was higher with environmental risk factor exposure and in underserved populations, suggesting greater unreported rates or lower quality healthcare affecting overall patient survival. TC may be linked to individuals' “social‐exposomes”, and early screening in these susceptible communities could provide the framework to implement sustainable preventive cancer control programs.

POSTER 286

Thyroid Cancer Clinical Poster

ELEVATING ADEQUACY: A META‐ANALYSIS OF RAPID ONSITE EVALUATION OF THYROID NODULES

Christina McCarthy*¹, Peter Issa², Aaron Albuck¹, Eslam Hossam³, Mohammad Hussein¹, Eman Toraih⁴, Emad Kandil¹

¹Tulane University School of Medicine, USA,²Louisiana State University School of Medicine, USA,³Surgical Oncology Department, National Cancer Institute, Cairo University, Egypt,⁴Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Egypt

Objective: Fine‐needle aspiration (FNA) is the standard form of pre‐operative evaluation of thyroid nodule cytological status. Still, a significant number FNAs are classified as inadequate for interpretation, requiring a repeat FNA which is potentially avoidable, costly, and delays treatment. To address these concerns, rapid onsite evaluation (ROSE) of FNA specimens was introduced. Our study aims to determine the impact of ROSE on FNA adequacy.

Methods: PubMed, Embase, and Web of Science were searched for primary articles assessing the adequacy of ROSE in thyroid nodules. Two investigators independently screened and extracted the data.

Results: A total of 17 studies were included for a total of 24,661 thyroid nodes. 13,227 (53.6%) thyroid nodules were assessed utilizing ROSE and 11,434 (46.4%) did not. Pooled adequacy increased significantly from 76% without ROSE to 92% with ROSE (p = 0.001). Use of ROSE increased the odds of adequate FNA by 22% (relative risk (RR) = 1.22, 95%CI = 1.12‐1.32, p < 0.001 ). In studies reported from hospitals with <85% effective diagnostic adequacy without ROSE, the relative risk for diagnostic adequacy increased by 28% with ROSE (RR = 1.28, 95%CI = 1.20‐1.37, p < 0.01). In studies reported from hospitals with an effective diagnostic rate ≥85% without ROSE, the diagnostic adequacy only increased by 5% (RR = 1.05, 95%CI = 1.03‐1.06, p = 0.69).

Conclusion: The use of ROSE during first‐time FNA of thyroid nodules can significantly improve adequacy, especially at institutions with high inadequacy rates. Implementation of ROSE can reduce repeat FNAs and its associated consequences. Future studies are warranted, especially cost‐effective analyses, to better expand on the consequences in ROSE implementation.

POSTER 287

Thyroid Cancer Clinical Poster

LYMPH NODE RATIO PREDICTS RECURRENCE IN PAPILLARY THYROID CARCINOMA WITH LOW LYMPH NODE YIELD

solji an*, il Ku Kang, Joonseon Park, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim

Department of Surgery, College of Medicine, The Catholic University of Korea, Korea, Republic of

Objective: The American Thyroid Association (ATA) risk stratifications system suggest that the number of metastatic lymph nodes (LNs) >5 increases the risk for recurrence in papillary thyroid carcinoma (PTC). However, little is known in terms of PTC with five or lesser harvested LNs. The aim of this study was to stratify the patients with low‐lymph‐node‐yield (low‐LNY) PTC according to lymph node ratio (LNR).

Methods: 6,317 patients who underwent thyroidectomy diagnosed with PTC at Seoul St. Mary's Hospital between January 2007 and December 2017 were initially collected. Of those, a total of 909 patients with one to five LNY after total thyroidectomy with central compartment neck dissection were included and retrospectively analyzed. Tumor recurrence were compared according to LNR. Receiver operating characteristic (ROC) curve was used to determine a cutoff.

Results: The mean follow‐up duration was 127.24 ± 33.6 (range, 5‐190) months. 46 patients (5.1%) experienced recurrence. The cutoff to divide the low (n = 675) and the high (n = 234) LNR group was 0.29 (AUC 0.676, 95% CI 0.591‐0.761, p < 0.001). Recurrence rates between the groups showed significant difference (2.5% vs. 12.4%, p < 0.001). In multivariate analysis using cox regression, tumor size and LNR ≥0.29 were independent prognostic factors for recurrence.

Conclusions: LNR can be used to risk‐stratify the patients with low‐LNY PTC.

POSTER 288

Thyroid Cancer Clinical Poster

ALL‐CAUSE AND CAUSE‐SPECIFIC MORTALITY AMONG INDIVIDUALS DIAGNOSED WITH LOW‐RISK DIFFERENTIATED THYROID CANCER

Thi Van Trinh Tran*¹, Sara Schonfeld¹, Elisa Pasqual², Megan Haymart³, Lindsay Morton¹, Cari Kitahara¹

¹Division of Cancer Epidemiology and Genetics National Cancer Institute, USA,²International Agency for Research on Cancer, France,³Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, USA

Objective: Differentiated thyroid cancer (DTC) is associated with excellent disease‐specific survival, particularly cases classified as low risk of recurrence. Individuals diagnosed with DTC might have elevated risks of second cancers and cardiovascular disease (CVD), yet little is known about how diseases other than DTC could contribute to mortality in this population. Therefore, we assessed all‐cause and cause‐specific mortality in individuals diagnosed with low‐risk DTC.

Methods: From the U.S. SEER‐12 cancer registry database (1992‐2019), we identified 51741 individuals (81.8% women) diagnosed with first primary, low‐risk (≤4 cm, localized) DTC. We estimated cause‐specific cumulative mortality by time since diagnosis, accounting for competing risks. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were used to compare observed mortality rates in DTC patients and expected rates in the matched U.S. general population, overall and by time since DTC diagnosis. Among low‐risk DTC patients, we used Cox proportional hazards models to examine the association between radioactive iodine (RAI) and cause‐specific mortality.

Results: During follow‐up (median 8.8 years, range 0–28 years), 3464 (6.7%) deaths were recorded. While thyroid cancer accounted for only 4.3% of deaths (n = 148), the most common causes were non‐thyroid cancer (n = 1030, 29.7%) and CVD (n = 911, 26.3%). The 20‐year cumulative mortality from thyroid cancer, non‐thyroid cancers, and CVD was 0.6%, 4.6%, and 3.9%, respectively. Compared to the general population, DTC patients had a lower‐than‐expected mortality from all causes other than thyroid cancer (SMR = 0.69, 95%CI 0.67‐0.72) and most specific causes, including non‐thyroid cancer (SMR = 0.80, 95%CI 0.75‐0.85), and CVD (SMR = 0.64, 95%CI 0.60‐0.69). However, mortality rates were elevated for cancers of the pancreas (SMR = 1.58, 95%CI 1.18‐2.06), kidney and renal pelvis (SMR = 1.85, 95%CI 1.10‐2.93), brain and other nervous system (SMR = 1.62, 95%CI 0.99‐2.51), myeloma (SMR = 2.35, 95%CI 1.46‐3.60) and leukemia (SMR = 1.62, 95%CI 1.07‐2.36), particularly after ≥10 years of DTC diagnosis. Based on limited number of cases, we found no association between RAI and specific mortality causes in DTC patients.

Conclusion: Overall, our data are reassuring regarding the low overall and cause‐specific mortality rates for individuals diagnosed with low‐risk DTC. For reasons that are unclear, this population experienced higher risks of death from certain cancer types in the long‐term (10+ years after diagnosis).

POSTER 289

Thyroid Cancer Clinical Poster

IMPACT ON TREATMENT RESPONSE OF A HIGHLY SELECTIVE RADIOACTIVE IODINE (RAI) TREATMENT STRATEGY IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA (DTC)

Carlos Garcia‐Regal*, Monica Gutierrez‐Guerrero, Paz Azpeitia‐Hernandez, Teresa Navarro‐Martinez, Hector Pian‐Arias, Ignacio Ruz‐Caracuel, Marta Araujo‐Castro, Alberto Martinez‐Lorca, Pablo Valderrabano

Ramon y Cajal University Hospital, Spain

Objective: To compare outcomes in patients with DTC before and after initiating a selective treatment strategy with RAI, based on recurrence risk and postsurgical response to therapy.

Methods: The medical records of all patients consecutively operated on at our institution for DTC between 01/2018 and 12/2021 were retrospectively evaluated. Only patients with follow‐up data were included. From 2019, RAI was restricted to high‐risk DTC; or intermediate‐risk DTC and biochemical incomplete response to surgery. RAI use, response to therapy at last follow‐up, and recurrence rate were compared between the two periods (2018 versus 2019‐2021).

Results: 234 patients were included (70 in 2018; 164 in 2019‐2021). Histology was: 84% papillary, 14% follicular or oncocytic, and 2% poorly differentiated. At diagnosis, 87% were classified as T1/T2 and 13% as T3/T4; 74% were N0/Nx and 26% N1a/b; 97% were Mx/M0 and 3% M1. According to 8th AJCC edition, 95% were stage I/II and 5% III/IV. The ATA risk of recurrence was low in 169 (72%), intermediate in 32 (14%), and high in 33 (14%). No differences were found in the T, M, stage or ATA risk, between the two period groups. There were more patients with lymph node metastases during the second period (16% vs 30%, p = 0.02). The risk of receiving RAI adjusted for the risk of recurrence was 95% lower during the second period. Among patients treated with RAI, there was no difference in mean dose. However, time to RAI was longer in the second period (121 versus 184 days from surgery date, p = 0.03). No differences were found in treatment response (excellent response 57% vs 60%; indeterminate 36% vs 29%; incomplete biochemical 4% vs 7%; incomplete structural 3% vs 4%, in 2018 and 2019‐2021 respectively, p = 0.61. During follow‐up, cancer recurrence was identified in 5 patients: 4 treated with RAI; and one previously treated by hemithyroidectomy alone. No differences in recurrence rate were observed (3% vs 2%, p = 0.62).

Conclusion: Delaying and‐or sparing RAI treatment in patients with low/intermediate‐risk DTC does not have a significant impact on recurrence rate or response to therapy at last follow‐up visit in the short term.

POSTER 290

Thyroid Cancer Clinical Poster

THE IMPACT OF RADIOACTIVE IODINE ON DISEASE SPECIFIC SURVIVAL BASED ON LYMPH NODE RATIO IN PAPILLARY THYROID CARCINOMA WITH LATERAL CERVICAL LYMPH NODE METASTASIS

Federico Palacardo*, Yeon Lee‐Saxton, Abhinay Tumati, Teagan Marshall, Daniel Hubbs, Rasa Zarnegar, Thomas Fahey III, Brendan Finnerty

Weill Cornell Medicine, USA

Objective: Elevated lymph node ratio (LNR, ratio of positive to excised) is associated with higher risk of recurrence and cancer‐related death in papillary thyroid carcinoma (PTC). Per the American Thyroid Association guidelines, it remains unclear if radioactive iodine (RAI) improves disease‐specific survival (DSS) in low‐to‐intermediate risk T1‐3 PTC with lateral cervical lymph node metastases. Herein, we aimed to evaluate the impact of RAI on DSS at multiple LNR thresholds in these patients.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients ≥18 years with pT1‐3, N1b, M0/Mx classic PTC treated with total thyroidectomy from 2004‐2015. Patient demographics, clinicopathologic characteristics, and outcomes were compared based on RAI administration. Multivariable Cox regression was performed to identify predictors of DSS. Subgroup analyses were conducted based on age and LNR cutoffs.

Results: RAI recipients were younger (43.0 vs. 44.0 years, p = 0.033) with higher rates of minimal extrathyroidal extension (22.9% vs. 19.2%, p < 0.001), rates of pericapsular soft tissue invasion (20.4% vs 16.6%, p < 0.001), and median LNR (0.367 vs. 0.333, p = 0.002). RAI recipients had similar median LNs examined (23 vs. 22, p = 0.301) but higher median positive LNs (7 vs. 6, p < 0.001). Worse DSS was associated with increasing age (adjusted HR = 1.09, CI [1.07‐1.10], p < 0.001), increasing tumor size (adjusted HR = 1.02, CI [1.01‐1.03], p < 0.001), and pericapsular soft tissue invasion (adjusted HR 2.20, CI [1.38‐3.49], p = 0.001). RAI was associated with improved DSS in the entire cohort (adjusted HR = 0.61, CI [0.41‐0.90], p = 0.014) and in patients ≥55 years (adjusted‐HR = 0.46, CI [0.30‐0.72] p = 0.001), but not in patients <55 years (adjusted‐HR = 0.79, CI [0.32‐1.99], p = 0.619). In patients <55 years, RAI was not associated with improved DSS at multiple LNR thresholds. In patients ≥55 years, RAI was associated with improved DSS in those with LNR >0.17 (adjusted‐HR = 0.44, CI [0.27‐0.72], p = 0.001) but not LNR ≤0.17 (adjusted‐HR = 0.60, CI [0.21‐1.72], p = 0.339).

Discussion/Conclusion: RAI administration is associated with improved DSS in older patients (age ≥55), particularly with LNR >0.17. LNR should be considered in future prospective studies examining the efficacy of RAI in patients with lateral cervical lymph node metastases.

POSTER 291

Thyroid Cancer Clinical Poster

SUBCUTANEOUS METASTASIS IN PAPILLARY THYROID CARCINOMA SURVIVORS

Eva Kruger*¹, Eman Toraih¹, Emad Kandil¹, Mohamed Hussein²

¹Tulane University School of Medicine, USA,²Tulane University School of Medicineo, USA

Objective: Papillary thyroid cancer (PTC) is the most common thyroid malignancy, comprising around 80% of all thyroid cancers. Prognosis is generally favorable, with cases of metastasis typically limited to cervical lymph node involvement. On rare occasion, metastasis occurs distally, and cutaneous involvement especially signals an underlying insidious, aggressive malignancy. Patients with cutaneous manifestations of PTC are found to have an average lifespan of a meager eight to 19 months. Literature investigating the pathophysiology of this disease is scarce. Thus, this meta‐analysis seeks to highlight potential clinical patterns to exploit in an effort to improve clinical outcomes of this truculent cancer.

Methods: A systematic literature review was conducted using multiple databases, searching for studies with relevant keywords for thyroid cancer and cutaneous metastasis. Case studies involving cutaneous metastasis of a prior thyroid malignancy were selected, with patients of any age, sex, and cancer subtype included. A total of 34 studies met these criteria for a total of 40 patients.

Results: Mortality findings were grim, with nearly 20% (n = 7) of patients dying in under six months following diagnosis of skin metastasis. Latency period was found to be inversely proportional to risk of mortality (p = 0.025), and metastasis presentation was found to be front‐loaded as a majority of patients died within five years of primary PTC diagnosis. Notably, cases involving the skin of the chest wall exhibited a five‐fold increase in mortality risk (p = 0.038). Of the cases included, 18 were stained for immunohistochemical (IHC) markers, all of which staining for thyroid transcription factor‐1 (TTF‐1). Positive results were found in all but one case. Additionally, 16 studies reporting IHC results stained for thyroglobulin (TG), in which all but one stained positive as well.

Conclusion: This meta‐analysis determined that latency period and chest wall metastasis may be viable predictors of mortality, cutaneous lesions exhibit sex‐dependent variation, and TG and TTF‐1 could be markers useful for hastening the identification of this malignancy, possibly expanding the window of treatment opportunity.

POSTER 292

Pediatrics Clinical Poster

INCIDENTAL PAPILLARY THYROID MICROCARCINOMAS IN PEDIATRIC PATIENTS FOLLOWING DEFINITIVE TREATMENT FOR GRAVES' DISEASE

Julia Baran*¹, Amber Isaza¹, Lindsay Sisko¹, Stephanie Robbins¹, Tricia Bhatti^1,2, Lea Surrey^1,2, N. Adzick^1,2, Ken Kazahaya^1,2, Andrew Bauer^1,2

¹Children's Hospital of Philadelphia, USA,²University of Pennsylvania, USA

Objective: Graves' Disease (GD) is an autoimmune thyroid condition that results in an overproduction of thyroid hormones. Interestingly, studies have suggested an association between GD and the development of thyroid cancer, with miRNA expression levels of GD falling between those euthyroid and those malignant. In the pediatric population, the incidence of clinically unsuspected papillary thyroid microcarcinomas (PTMCs) in patients with GD has not been well described. This study reports our institutional experience with a cohort of pediatric patients who pursued total thyroidectomy (TT) for definitive treatment of GD.

Methods: Medical history, clinicopathologic characteristics, and treatment outcomes were extracted for GD patients who underwent TT at the Children's Hospital of Philadelphia between August 2010‐February 2023. PTMC (<10mm) was characterized as incidental in the absence of thyroid nodule(s) and adenopathy on preoperative examination.

Results: Of 245 GD patients, 5% (12/245) presented with incidental PTMCs. Patients with PTMCs underwent TT at a median age of 17.2 years (IQR = 16.1‐17.7; range = 13.5‐19.4) and had a median tumor size of 2.0 mm (IQR = 1.0‐3.5; range = 1.0‐9.0). Classic variant was the most common histologic subtype (4/12), followed by mixed classic, follicular, and/or oncocytic variants (2/12), and follicular variant (1/12). Histologic subtype was not specified for five patients. Multifocality was observed in three patients, with one patient demonstrating minimal extrathyroidal extension. Half (6/12) of patients had incidental lymph nodes removed from the central neck compartment (median = 2 LNs; IQR = 1‐4; range = 1‐9), and 100% (6/6) demonstrated no evidence of regional metastasis (AJCC N0a). Thyroglobulin (Tg) and Tg Antibodies (TgAb) were followed postoperatively in half (6/12) of patients. None (0/12) presented with clinically evident persistent or recurrent thyroid cancer at last evaluation (median = 3.1 years; IQR = 1.4‐3.9).

Discussion/Conclusion: The prevalence of incidental PTMC in pediatric patients with GD is low and is associated with a low risk of regional and distal metastasis. For the majority of patients, following Tg and TgAb may not be informative and difficult to interpret based on the presence of thyroid remnant and time for resolution of elevated TgAb titer levels.

POSTER 293

Thyroid Cancer Clinical Poster

LOWER THYROID CANCER‐SPECIFIC MORTALITY IN PATIENTS WITH A HISTORY OF BREAST CANCER

Shuhuang Lin*, Mingzhao Xing

School of Medicine, Southern University of Science and Technology, China

Objective: Numerous studies have reported an epidemiological association between thyroid cancer (TC) and breast cancer (BC). Our previous studies have demonstrated a lower BC‐specific mortality in patients with a history of TC compared with those without TC [1]. Our objective here was to investigate whether there is also an impact of the association between the two cancers on the clinical outcomes of TC.

Methods: We utilized the Surveillance, Epidemiology and End Results (SEER) 18 database [2] to analyze TC tumor behaviors and TC‐specific survival in patients with a history of BC (TC‐BC), including those diagnosed with TC before BC (TC‐1st) and those diagnosed with TC after BC (BC‐1st), compared to patients without a history of BC (TCnoBC), using a 1:5 propensity score matching (PSM).

Results: Of 10,450,709 case records in the database, 5,598 patients with papillary thyroid cancer (PTC) and 604 patients with follicular thyroid cancer (FTC) were identified to have a history of BC (TC‐BC) from 1983 to 2016. We found that in both PTC and FTC, TC had less aggressive tumor behaviors and clinical outcomes in TC‐BC patients compared with matched TCnoBC patients, including a lower rate of distant metastasis and TC‐specific mortality. In Cox regression analysis, a history of BC had a stronger protective effect on TC‐specific survival in TC‐1st patients (HR = 0.397, P < 0.001) than in BC‐1st patients (HR = 0.607, P = 0.002), while in FTC, this effect was restricted to TC‐1st (HR = 0.458, P = 0.007). Further analysis revealed that the estrogen receptor (ER) positivity of BC was associated with an additional survival advantage in TC‐1st patients in PTC (HR = 0.326, P = 0.019). These relations remained significant after adjustment for social economic status and clinicalopathological factors.

Discussion/Conclusion: Our results have revealed a clinically distinct entity of TC characterized by less aggressive tumor behaviors and lower patient mortality when the patient also has a history of BC. The role of ER positivity revealed to be involved suggests that this is a biologically unique entity, whose molecular mechanism needs to be further investigated.

POSTER 294

Surgery Clinical Poster

THYROID HORMONE REPLACEMENT AFTER HEMITHYROIDECTOMY – A SINGLE INSTITUTION STUDY

John Sun*, Georgia Morrison, Maisie Shindo, Olga Senashova, James Lim

Oregon Health & Science University, USA

Objective: Hemithyroidectomy can be an appropriate treatment for symptomatic thyroid nodules and low risk cancers (1). Although preserving residual thyroid function, hypothyroidism is still a well‐known risk and thyroid hormone replacement (THR) rates are around 30%‐40%. Recent studies have shown that this risk can be much higher (2,3). Our objective is to evaluate the rate of post‐operative THR after hemithyroidectomy at our institution, as well as delineate risk factors that could predict postoperative THR.

Methods: We conducted an IRB approved retrospective study looking at patients who underwent initial hemithyroidectomy at our institution between 2014‐2017. Basic demographic characteristics, evidence of thyroiditis on pathology, presence of cancer, and thyroid function (TSH, pre/postoperative) of these patients were collected from electronic medical records. We excluded patients with preoperative hypothyroidism, with non‐thyroid tumors and those who underwent completion hemithyroidectomy. Binomial logistical regression was used to evaluate predictive factors for needing postoperative THR.

Results: Our study included 216 patients who underwent initial hemithyroidectomy. The average age of patients at the time of surgery was 47‐years‐old and 82% were female. The average follow‐up post‐hemithyroidectomy was 6 years. Overall, 99 patients (46%) needed post‐operative thyroid hormone replacement. In thyroid cancer patients (n = 74), 62% required THR. In benign thyroid patients, (n = 142), 37% required THR. Risk factors for THR on logistical regression analysis included patients with a cancer diagnosis (OR = 4.28, 95% CI [2.14‐8.54]) and patients with a preoperative TSH level >2μIU/mL (OR = 3.27, 95% CI [1.55‐6.89]). Of cancer patients who were started on THR, 74% had an initial post‐operative TSH level within the normal reference range (0.45μIU/mL–5.33μIU/mL).

Discussion/Conclusion: Our postoperative THR rates in benign thyroid patients was in line with previous studies. In thyroid cancer patients, this rate is much higher. This is likely due to ATA guidelines recommending a postoperative TSH between 0.5‐2.0 μIU/mL for thyroid cancer patients (1). Our study identified two independent risk factors for THR, cancer pathology and preoperative TSH >2μIU/mL. Known cancer or suspected cancer patients should be counseled about this higher risk of THR, even in the setting of a normal postoperative TSH.

ORAL 14

Thyroid Cancer Clinical Oral

ESTIMABL 2 TRIAL: THYROIDECTOMY WITHOUT RADIOIODINE IN PATIENTS WITH LOW‐RISK THYROID CANCER: 5 YEARS OF FOLLOW‐UP

Sophie Leboulleux*^1,2, Claire Bournaud³, Cecile Chougnet⁴, Livia Lamartina¹, Slimane Zerdoud⁵, Christine Do Cao⁶, Bogdan Catargi⁷, Inna Dygai⁸, Antony Kelly⁹, Marie Luce Barge¹⁰, Pierre Vera¹¹, Daniela Rusu¹², Olivier Schneegans¹³, Julie Roux¹⁴, Marc Klein¹⁵, Danielle Benisvy¹⁶, Marie‐Claude Eberle¹⁷, Sophie Bidault¹, Camila Nascimento¹⁸, Delphine Bastie¹⁹, Anne‐Laure Giraudet²⁰, Stéphane Bardet²¹, Nathalie Le Moullec²², Nathalie Roudaut²³, Delphine Drui²⁴, Yann Godbert²⁵, Mohamad Zalzali²⁶, Anne Drutel²⁷, Olivier Morel²⁸, Fritz‐Line Velayoudom²⁹, Abir Al Ghuzlan¹, Martin Schlumberger¹, Camille Buffet³⁰, Isabelle Borget¹

¹Gustave Roussy, France,²Hôpitaux Universitaires de Genève, Switzerland,³Hospices Civils de Lyon, France,⁴Hôpital Saint Louis, France,⁵IUCT Oncopole, France,⁶CHRU de Lille–Hôpital Claude Huriez, France,⁷Hôpital Saint‐André Centre Hospitalier Universitaire de Bordeaux, France,⁸Centre Georges François Leclerc, France,⁹Centre Jean Perrin, France,¹⁰Centre Eugene Marquis, France,¹¹Centre Henri Becquerel, France,¹²Centre René Gauducheau, France,¹³Centre Paul Strauss, France,¹⁴CHU Grenoble–Alpes, France,¹⁵Centre Hospitalier Régional Universitaire (CHRU) de Nancy, France,¹⁶Centre Antoine Lacassagne, France,¹⁷Institut Régional du Cancer Val d'Aurelle, France,¹⁸, Institut Curie Site Saint‐Cloud, France,¹⁹CHU Rangueil, France,²⁰Centre Léon Bérard, France,²¹Centre François Baclesse, France,²²CHU Saint Pierre, France,²³CHU La Cavale Blanche, France,²⁴CHU de Nantes–Hopital Laennec Saint‐Herblain, France,²⁵Institut Bergonié, France,²⁶Institut Jean Godinot, France,²⁷CHU Dupuytren, France,²⁸Institut de Cancérologie de l'Ouest, France,²⁹CHU Guadeloupe, France,³⁰Pitié–Salpétrière Hospital AP–HP, France

Background: ESTIMABL2 is a prospective randomized phase III trial in low‐risk differentiated thyroid cancer (DTC) patients evaluating a follow‐up strategy without 131I administration (no‐radioiodine group) in comparison to post‐operative 131I administration (1.1 GBq‐30 mCi after rhTSH (radioiodine group). The results demonstrated the non‐inferiority of the proportion of patients without event in the no‐radioiodine group as compared to the iodine‐group assessed 3 years after randomization. A longer follow‐up was scheduled and is reported here.

Methods: This multicentric randomized phase III trial included patients with low‐risk DTC (T1am or T1b and N0/Nx) treated with total thyroidectomy +/‐ prophylactic neck lymph node dissection. Two to five months after surgery, in the absence of suspicious neck lymph node on ultrasonography (US), patients were randomized to the no‐radioiodine group or to the radioiodine group. Follow‐up consisted in yearly TSH, thyroglobulin (Tg) and Tg antibodies (Tg‐Ab) determinations on levothyroxine treatment and neck‐US in odd number years.

An event was defined by abnormal foci of 131I uptake on the post‐therapy whole‐body‐scan requiring subsequent treatment and/or abnormal neck‐US and/or by elevated Tg levels and/or rising titres or appearance of Tg‐Ab.

One objective was to assess the non‐inferiority of the proportion of patients without event in the no‐radioiodine group as compared to the radioiodine group at 5 years after randomization. Non‐inferiority was demonstrated if this proportion did not differ by more than ‐5%.

Results: Among 776 low‐risk DTC patients included between 2013 and 2017 in 35 French centers within the TUTHYREF network, 730 were evaluable 3 years after randomization and 698 were evaluable at 5 years.

The proportion of patients without event during these 5 years of follow‐up were 92.1% CI95% = [88.8‐94.7] in the no‐radioiodine group and 94.5% CI95% = [91.5;96.6] in the radioiodine group, leading to a difference of 2.4% CI90% = [‐5.5%; 0.7%], demonstrating that a no radioiodine strategy was non‐inferior to radioiodine. Events consisted of structural/functional abnormalities (n = 13) and biological abnormalities (n = 39). Events were more frequent in patients with post‐operative serum thyroglobulin level on levothyroxine >1ng/mL.

Conclusions: This analysis confirmed that in low‐risk DTC patients the non‐inferiority of a follow‐up strategy compared to post‐operative administration of 131I (PHRC 2012; NCT01837745).

ORAL 15

Thyroid Cancer Translational Oral

MOLECULAR CHARACTERISTICS DISTINGUISH RADIATION‐INDUCED VERSUS SPORADIC PAPILLARY THYROID CARCINOMAS AFTER THE CHORNOBYL NUCLEAR POWER PLANT ACCIDENT

Lindsay Morton*¹, Danielle Karyadi¹, Cato Milder¹, Tetiana Bogdanova², Elizabeth Cahoon¹, Chip Stewart³, Stephen Hartley¹, Sara Schonfeld¹, Vladimir Drozdovitch¹, Sergii Masiuk⁴, Mykola Chepurny⁴, Liudmyla Yu Zurnadzhy², Marko Krznaric⁵, Meredith Yeager¹, Olivia Lee¹, Vibha Vij¹, Cari Kitahara¹, Gayle Woloschak⁶, Kiyohiko Mabuchi¹, Amy Berrington de Gonzalez¹, Gad Getz³, Gerry Thomas⁵, Mykola Tronko², Stephen Chanock¹

¹National Cancer Institute, USA,²V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine, Ukraine,³Broad Institute of MIT and Harvard, USA,⁴National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Ukraine,⁵Imperial College London, Charing Cross Hospital, United Kingdom,⁶Northwestern University, USA

Tumors occurring after radiation exposure have increased frequencies of deletions, structural variants, and fusion drivers. These characteristics reflect DNA double‐strand breaks (DSBs) but are not necessarily unique biomarkers for radiation‐induced cancers because they can be caused by other exogenous exposures and endogenous processes.

We undertook two orthogonal analyses to attempt to distinguish radiation‐induced versus sporadic tumors using high‐quality whole genome sequence data from fresh‐frozen papillary thyroid carcinomas (PTCs) occurring in radioactive iodine (¹³¹I)‐exposed individuals after the Chornobyl nuclear power plant accident (Morton et al., Science 2021). We separately analyzed PTCs with the most common primary oncogenic drivers: fusions (most commonly involving RET or another receptor tyrosine kinase; N = 112) versus BRAF^V600E substitution (N = 132).

We first hypothesized radiation dose would be associated with DNA DSBs in radiation‐induced but not sporadic PTCs. Multivariable regression models adjusting for sex and age at PTC diagnosis demonstrated associations between dose and clonal small deletions for PTC with fusion drivers (deletions/100 mGy, 95% confidence interval [CI_95%]: 1.2 [0.53,1.88], P = 6.1x10⁻⁴) but not BRAF^V600E (0.56 [‐0.21,1.33], P = 0.15). The radiation association with other DNA DSB metrics (ratio of clonal deletions:single nucleotide variants, occurrence of COSMIC insertion‐deletion signature 8 (ID8), and occurrence of simple/balanced structural variants) was similarly restricted to fusion‐driven PTC. We then leveraged mutational signature analysis to identify age‐associated “clock” mutations (COSMIC single base substitution signatures 1 and 5). Because clonal clock mutations in tumor cells represent accumulated clock mutations at tumor initiation, we hypothesized the number of clonal clock mutations would correlate with age at the Chornobyl accident for radiation‐induced (i.e., induced at the time of the accident) but not sporadic tumors. Multivariable regression models adjusting for sex and age at PTC demonstrated that age at the accident was related to clonal clock mutations for PTC with fusion drivers (clonal clock mutations/year of age [CI_95%]: 12.0 [7.2,16.8], P = 3.0x10⁻⁶) but not BRAF^V600E (0.16 [‐3.9,4.2], P = 0.94).

These results support associations between radiation dose from the Chornobyl accident and PTC with fusion but not BRAF^V600E drivers, suggesting radiation differentially induces fusion‐driven over BRAF^V600E ‐driven PTC. Our findings offer further insights into radiation carcinogenesis and could be useful for determining probability of causation.

ORAL 16

Thyroid Cancer Translational Oral

TAKING ADVANTAGE OF THE INTERLEUKIN‐6‐BIOLOGY IN DIFFERENTIATED THYROID CANCER TO STIMULATE SODIUM IODIDE SYMPORTER (NIS)‐MEDIATED IODIDE UPTAKE IN ENGINEERED MESENCHYMAL STEM CELLS

Viktoria Koehler*¹, Leandro Drago¹, Mara Hageneier¹, Carolin Kitzberger², Nathalie Schwenk¹, Khuram Shehzad¹, Peter Nelson¹, Christine Spitzweg^1,3

¹Department of Internal Medicine IV, Germany,²Department of Nuclear Medicine at Klinikum Rechts der Isar and Central Institute for Translational Cancer Research (TranslaTUM), Germany,³Adjunct Academic Appointment, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, USA

Objective: The sodium iodide symporter (NIS) provides the basis for the use of radioiodine (RAI) for diagnostic imaging and therapy of differentiated thyroid cancer (DTC). The delivery of NIS as a transgene into the tumor microenvironment using mesenchymal stem cells (MSCs) represents a therapeutic strategy for RAI‐refractory DTC due to their exceptional tumor‐homing capacity. MSCs engineered to drive NIS transgene expression in response to IL‐6‐promoter activation may offer the possibility of a new tumor‐targeted gene therapy approach of RAI‐refractory DTC. Therefore, MSCs were stably transfected with a NIS‐expressing plasmid controlled by the human IL‐6‐promoter (IL‐6‐NIS‐MSCs) to selectively drive NIS‐transgene expression in the context of DTC.

Methods: IL‐6‐NIS‐MSCs were incubated with cytokines (IL‐1 β, TNF‐α and IFN‐γ) that are well known strong activators of the IL‐6 pathway, as well as with tumor cell conditioned medium (CM) derived from papillary thyroid cancer cell lines K1 and BCPAP, followed by analysis of the resulting functional NIS expression by ¹²⁵I uptake assay in vitro. Chemotactic behavior of IL‐6‐NIS‐MSCs subjected to a gradient of serum free tumor cell‐CM of K1 and BCPAP as well as serum free unconditioned medium was evaluated using 3D live‐cell imaging migration assay over a period of 24 h. For a preliminary in vivo study, IL‐6‐NIS‐MSCs were applied via the tail vein to mice harboring subcutaneous K1 tumors and tumoral iodine uptake was monitored by ¹²³I‐scintigraphy.

Results: IL‐6‐NIS‐MSCs treated with IL‐1 β, TNF‐α and IFN‐γ revealed significantly increased, perchlorate‐sensitive ¹²⁵I uptake. Incubation of IL‐6‐NIS‐MSCs with BCPAP‐CM and K1‐CM containing diverse tumor‐derived factors or directly co‐cultured with these cell lines resulted in significant increase of ¹²⁵I uptake. IL‐6‐NIS‐MSCs subjected to a gradient between serum free tumor cell‐CM and serum free unconditioned medium, showed an increased migration towards tumor cell‐CM. In the in vivo biodistribution study, tumor‐selective iodine uptake was effectively induced in K1 xenografts after systemic injection of IL‐6‐NIS‐MSCs. The images revealed a maximum tumoral iodide accumulation one hour post ¹²³I injection with approximately 5.57 ± 0.92% of the injected dose per tumor in K1 subcutaneous tumors.

Conclusion: In conclusion, the application of MSC‐mediated NIS gene therapy focusing on IL‐6‐biology‐induced NIS transgene expression represents a promising approach for the reestablishment of radioiodine therapy in radioiodine‐refractory DTC.

ORAL 17

Thyroid Cancer Clinical Oral

A PROSPECTIVE, MULTICENTER STUDY OF MOLECULAR‐BASED INITIAL THYROIDECTOMY FOR BETHESDA V/VI CYTOLOGY

Linwah Yip*¹, Tracy Wang², Kelly McCoy¹, Sophie Dream², Kimberly Ramonell¹, Esra French¹, Elena Morariu¹, N Paul Ohori¹, Marina Nikiforova¹, Yuri Nikiforov¹, Sally Carty¹

¹University of Pittsburgh, USA,²Medical College of Wisconsin, USA

Objective: Improvements in preoperative risk stratification are needed to inform extent of initial thyroidectomy for papillary thyroid cancer (PTC) patients. Molecular testing (MT) detects genetic alterations which are associated with risk of disease recurrence. To our knowledge, the use of preoperative MT for directing extent of surgery has not been prospectively tested. We aimed to assess if initial thyroid lobectomy (TL) or total thyroidectomy (TT) can be accurately guided by preoperative MT in Bethesda [B]V and VI nodules.

Methods: We performed a multicenter phase 2 prospective trial of adult patients with nodules 1‐4 cm and BV/VI FNA results who otherwise had no clinical factors which would direct extent of initial surgery. Staging neck ultrasound was used to exclude findings indicating TT such as contralateral nodules ≥1 cm, suspicious lymphadenopathy, or extrathyroidal extension. Study design included preoperative MT with TL for MT low‐risk results (RAS‐like) or TT for MT intermediate (BRAF‐like) and high‐risk alterations. Primary outcome was extent of thyroidectomy according to the American Thyroid Association (ATA) risk stratification system.

Results: Of 89 patients, the mean nodule size was 1.9 ± 0.6 cm, mean age 46.6 ± 15 yrs, 29% were male, and 26 (29%) had BV FNA results. Positive MT occurred in 83 (93%) nodules. Of 16 (18%) patients with MT low‐risk or negative results who had initial TL, 3 had benign nodules, 3 NIFTP, and 10 had ATA Low‐Risk disease. For 68 (76%) MT intermediate‐risk results, TT was performed in all but 1 patient, and ATA Low‐, Intermediate‐ and High‐Risk PTC was histologically present in 42 (62%), 22 (32%) and 4 (6%) patients, respectively. For the 5 (6%) patients with high‐risk alterations (2 BRAF V600E/TERT, 2 BRAF V600E/CNA, and 1 BRAF V600E/TP53), TT was performed and all had ATA Intermediate‐Risk disease.

Conclusions: Based on immediate post‐operative ATA risk stratification by histology, appropriate initial TL and TT occurred for all patients with MT low‐ and high‐risk alterations. However, MT intermediate‐risk results (typically BRAF‐like) were associated with histologies in all 3 ATA risk categories. The patients are being followed to monitor for tumor recurrence while additional clinical factors will be explored in order to continue refining optimal initial extent of surgery.

ORAL 18

Surgery Clinical Oral

DECISION REGRET AFTER CHOOSING SURGERY OR ACTIVE SURVEILLANCE FOR MANAGEMENT OF SMALL, LOW RISK PAPILLARY THYROID CANCER: RESULTS OF A PROSPECTIVE COHORT STUDY

Anna Sawka*^1,2, Sangeet Ghai^3,2, Lorne Rotstein^1,2, Jonathan Irish^1,2, Jesse Pasternak^1,2, Eric Monteiro^4,2, Jie Su⁵, Wei Xu^5,2, Amiram Gafni⁶, Nancy Baxter⁷, David Goldstein^1,2

¹University Health Network, Canada,²University of Toronto, Canada,³Joint Department of Medical Imaging, University Health Network‐Mt Sinai Hospital‐Women's College Hospital, Canada,⁴Mount Sinai Ho, Canada,⁵Princess Margaret Cancer Centre, Canada,⁶McMaster University, Canada,⁷Melbourne School of Population and Global Health, University of Melbourne, Australia

Objective: We examined the level of decision regret in individuals with small, low risk papillary thyroid cancer (PTC) who were offered the choice of surgery or active surveillance (AS).

Methods: We performed a prospective observational cohort study in Toronto, Canada (Clinicaltrials.gov: NCT03271892). One year after offering patients with small, low risk PTC (< 2 cm in maximal diameter), the choice of either surgery or AS, we asked participants to complete a written questionnaire and we reviewed their study follow‐up data as well as relevant medical records. The primary analysis was description of the decision regret scale total score, pertaining to the initial choice of surgery or AS (scored on a scale of 0 to 100, where 100 is the worst). Descriptive statistics were reported and we performed a linear regression analysis exploring the relationship between 1‐year study treatment status and the level of decision regret.

Results: The response rate was 95.5% (191/200). The initial treatment choices of respondents were: AS in 79.1% (151/191) and surgery in 20.9% (40/191). The mean participant age was 53 years (standard deviation, SD 15 years) and 77% (147/191) were women. The mean baseline primary tumor size was 11 mm (SD 4). In the AS group, 6.6% (10/151) of patients crossed over to surgery or ablative treatment (only one of whom had disease progression meeting study criteria prior to surgery). The mean level of decision regret was 22 (SD 14) and this did not differ significantly between those who initially chose AS (mean 22, SD 14) or surgery (mean 21, SD 12) (p = 0.73). In comparison to patients who remained under AS, the risk of worse 1‐year decision regret was not significantly different in patients who initially chose surgery (relative risk [RR] 0.97, 95% confidence intervals [CI] 0.90, 1.05), but it was significantly higher in those who crossed over (RR 1.66, 95% CI 1.48, 1.85).

Discussion/Conclusion: In this prospective study of patients with small, low risk PTC, the level of decision regret pertaining to the initial disease management was generally relatively low and did not differ significantly differ according to the initial choice of AS or surgery.

ORAL 19

Thyroid Cancer Clinical Oral

SURGICAL AND ONCOLOGIC OUTCOMES AFTER CONVERSION SURGERY FOR PATIENTS WITH LOW‐RISK PAPILLARY THYROID CARCINOMA INITIALLY FOLLOWED WITH ACTIVE SURVEILLANCE

Helena Levyn*, Daniel Scholfield, Alana Eagan, Ashok Shaha, Richard Wong, Jatin Shah, Ian Ganly, Luc Morris, Robert Tuttle

Memorial Sloan Kettering Cancer Center, USA

Objective: To assess the safety and oncologic outcomes of patients undergoing conversion surgery (CS) due to concern for disease progression after a period of active surveillance (AS) for low‐risk papillary thyroid cancer (PTC).

Methods: From a prospective registry of 559 patients followed with AS for low‐risk PTC, this analysis of patients undergoing CS evaluated the indication for surgery, intraoperative findings, surgical complications, pathologic characteristics and overall survival (OS) and the cumulative incidence rate (CIR) of recurrence, calculated using the Kaplan‐Meier method.

Results: Of 559 AS patients, 42 patients (7.5%) underwent CS due to suspected disease progression. The median duration of AS in this group was 28 months (IQR 15,67). The primary indication for CS was tumor growth (45%,n = 19), followed by suspected extrathyroidal extension(ETE) (40%), tumor proximity to the thyroid capsule (17%), and detection of metastatic lymph nodes (all in the lateral neck; 9.5%, n = 4). In 28 (67%) patients, CS consisted of lobectomy; and in 14 individuals (33%) total thyroidectomy with or without neck dissection. At the time of surgery, the cancer was found to be adherent to the recurrent nerve in 1 case (2.4%), with normal vocal cord function postoperatively. There was 1 separate case of postoperative vocal cord paresis, unrelated to the index cancer. There were no cases of permanent hypocalcemia, and 2 cases of seroma (4.8%). On final surgical pathology, 95% of tumors were AJCC 8th Edition stage I (n = 40), and 2 (4.9%) were stage II. Histological subtypes were classical PTC (57%, n = 24), tall cell subtype (n = 13, 31%), follicular subtype (n = 4,9.5%), and differentiated high‐grade thyroid carcinoma (n = 1, 2.4%). Of the cases with suspected ETE as the indication for CS (n = 17), ETE was confirmed pathologically in 8 cases (47%). Postoperative radioiodine was administered in 3 patients (7.1%). The median follow‐up time after surgery was 39 months (IQR 18,57.5). The 5‐year OS rate was 100%, 5‐year CIR for recurrence was 13.4% (all nodal recurrences).

Discussion: In our prospective AS cohort, 7.5% of patients have undergone CS due to suspicion of disease progression. These patients underwent curative surgery without evidence of escalated risk of complications, diminished survival or recurrence outcomes.

ORAL 20

Thyroid Cancer Clinical Oral

CAN ULTRASOUND‐GUIDED ETHANOL ABLATION ACHIEVE DURABLE LONG‐TERM CONTROL OF RECURRENT NECK NODAL METASTASES OCCURRING AFTER POTENTIALLY CURATIVE BILATERAL THYROIDECTOMY AND POSTOPERATIVE RADIOIODINE THERAPY IN ADULT PATIENTS WITH NODE‐POSITIVE AJCC PTNM STAGE I PAPILLARY THYROID CARCINOMA

Ian Hay*, Robert Lee, Carl Reading, William Charboneau

Mayo Clinic, USA

Objective. An international expert panel recently approved (Head Neck 2022; 44:633) ethanol ablation (EA) as a “suitable first‐line therapy” for neck nodal metastases (NNM) in adult papillary thyroid carcinoma (APTC) patients. Durability of results beyond 60 months in this setting has rarely been reported (JCEM 2022; 107:e2141). In this study we describe outcome results of EA in successfully controlling 71 recurrent NNM in 41 stage I APTC patients followed on average for 159 months.

Methods. For study inclusion all 41 node‐positive stage I APTC patients were treated with bilateral thyroidectomy (BT), extensive nodal resection and radioactive iodine (RAI) therapy and were followed at our institution with neck ultrasound (US) exams for at least 48 months after EA. Each received a median cumulative RAI dose of 150 mCi (range 30‐550); before EA 28 patients (68%) had 41 additional neck surgeries with resultant postoperative unilateral cord paresis (UCP) in four. The cytologic diagnosis of PTC in 71 NNM (volume range 12‐1404 mm³; median 150) selected for EA was confirmed by US‐guided biopsy. EA technique and follow‐up protocol details were as previously described (JES 2020; 4:bvaa095).

Results. The 41 patients (26 women, 15 men; median age 36 yr) each had 1‐4 NNM (median 1). 67/71 NNM (94%) received 2‐4 (median 2) ethanol injections (total volume ranged 0.2‐3.0 mL; median 0.8). Post‐EA all 71 ablated NNM (46% at levels 6/7) shrank (mean volume reduction of 93%) and nodal hypervascularity was eliminated. 39 NNM (55%) with initial volumes of 12‐1404 mm³ (median 164) disappeared on neck sonography. 32 hypovascular foci from ablated NNM (pre‐EA volume range 31‐636 mm³; median 147) were identifiable with volume reductions of 13‐98% observed (median 81%). There were no complications and no post‐procedure hoarseness. EA was successfully performed in 3 patients with known UCP on 5 NNM (3 central; 2 lateral) situated on the side of the neck associated with intact recurrent laryngeal nerve function; 4/5 (80%) disappeared. Median post‐EA serum thyroglobulin (range <0.1 – 1.4 ng/mL) on TSH‐suppressive treatment in 39 patients was 0.2 ng/mL. Latest follow‐up ranged from 5.2 to 22.4 years (median value of 14.1 years).

Conclusions. EA of NNM in stage I APTC is effective and safe. Our results demonstrate that for patients with AJCC stage I APTC, who do not wish further surgery or RAI and are uncomfortable with active surveillance, EA can achieve durable long‐term control of recurrent NNM.

ORAL 21

Thyroid Hormone Action Metabolism and Regulation Basic Oral

PERTURBATION OF ENDOPLASMIC RETICULUM PROTEOSTASIS TRIGGERS TISSUE INJURY IN THE THYROID GLAND

XIAOHAN ZHANG*¹, Crystal Young^1,2, Xiao‐Hui Liao³, Samuel Refetoff^3,4, Mauricio Torres², Yaron Tomer⁵, Mihaela Stefan‐Lifshitz⁵, Hao Zhang¹, Dennis Larkin¹, Deyu Feng⁶, Ling Qi², Peter Arvan¹

¹1Division of Metabolism, Endocrinology & Diabetes, University of Michigan, USA,²2Department of Molecular & Integrative Physiology, University of Michigan, USA,³3Department of Medicine, The University of Chicago, USA,⁴4Pediatrics and Committee on Genetics, The University of Chicago, USA,⁵5Department of Medicine, Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, USA,⁶6Department of Pathology, Feinberg/Northwestern School of Medicine, USA

Introduction: Misfolded secretory proteins accumulate in the endoplasmic reticulum (ER) when their folding requirements exceed ER protein folding capacity, triggering ER stress. To limit ER stress, maintenance of ER homeostasis requires active mechanisms for the clearance of misfolded secretory proteins, such as ER‐associated degradation (ERAD), and ER macroautophagy. Thyroglobulin (Tg, the precursor protein for thyroid hormone synthesis) is the most highly expressed gene product in the thyroid gland, and one of the largest proteins in the vertebrate secretome. Tg folding represents a major challenge to thyrocyte proteostasis. Misfolding‐inducing TG mutations are common in humans but are said to yield only autosomal‐recessive disease. The fate of misfolded Tg (both mutant and wildtype) remains unclear.

Methods: We studied mice bearing one of three genetic defects: thyrocyte‐specific HRD1 deletion (defective for ERAD), thyrocyte‐specific ATG7 deletion (defective for autophagy), and TG^cog/+ heterozygotes (one allele encoding misfolded mutant Tg) — as well as double mutants of TG^cog/+ in a background of HRD1 or ATG7 deletion.

Results / Discussion: We find that thyrocyte‐specific deficiency of either HRD1 or ATG7 mice have relatively normal thyroid histology, circulating TSH, as well as total T₄ and T₃ levels. In contrast, heterozygous TG^cog/+ mice exhibit subclinical hypothyroidism (increased TSH with normal T₄ and T₃ levels), an enlarged thyroid (typical TSH‐driven compensatory response) and a massive expansion of the thyrocyte ER accompanied by dramatic elevation of ER stress markers (BiP, ERdj6, and CHOP) as well as cleaved PARP (marker of cell death). TUNEL staining revealed numerous dead thyrocytes in the lumen of TG^cog/+ thyroid follicles. These phenotypes are limited in animals treated with levothyroxine. Double mutant TG^cog/+,ATG7^TPO mice show little incremental deficits beyond those seen in TG^cog/+ heterozygotes, with comparable levels of BiP, ERdj6, cleaved PARP and TUNEL‐positive follicles. However, TG^cog/+,HRD1^TPO double mutants exhibit overt hypothyroidism with low serum T₄ and a further increase of TSH. Moreover, thyroid histology of TG^cog/+,HRD1^TPO mice reveals follicle collapse and degeneration (multiply TUNEL‐positive), accompanied by infiltration of bone marrow‐derived macrophages.

Conclusions: Although clinically silent, heterozygous expression of misfolded Tg, so common in the human population, involves ongoing large‐scale ER stress‐mediated cell death. Whole follicle death in heterozygous TG mutations with accompanying ERAD deficiency raises the possibility that thyrocytes may require ERAD for the degradation of mutant Tg protein in order to prevent the development of hypothyroidism.

ORAL 22

Thyroid Hormone Action Metabolism and Regulation Basic Oral

COCHLEAR DEVELOPMENT AND AUDITORY FUNCTION IN A MOUSE MODEL OF ALLEN‐HERNDON‐DUDLEY SYNDROME

Richard Sinn¹, Stephanie Peterson¹, Natalie Moses¹, Emily Gregersen¹, Prathibha Mangedarage¹, Douglas Forrest², Heike Heuer³, David Sharlin*¹

¹Minnesota State University, USA,²NIDDK, NIH, USA,³Clinic for Endocrinology, Diabetes & Metabolism, University Hospital Essen, Germany

Allen‐Herndon‐Dudley Syndrome (AHDS) is a complex X‐linked disorder that results from inactivating mutations in the SLC16A2 gene that encodes the monocarboxylate transporter 8 (Mct8) protein, a relatively selective thyroid hormone (TH) membrane transporter. AHDS is characterized by severe neurological and motor impairments. Additionally, patients have elevated serum T3, normal/low T4, and normal/elevated TSH. The working hypothesis reasons that the neurological impairments in AHDS are the result of decreased TH uptake into the developing brain. Inactivation of Mct8 in mice recapitulates the abnormal TH serum profile seen in AHDS, but results in only minor neurological impairments. Concomitant inactivation of the organic anion transporting polypeptide 1C1 (Oatp1c1) with Mct8 results in a phenotype that mirrors that of AHDS. As such, mice lacking Mct8 and Oatp1c1 (double knockout mice) are seen as a model for the disorder.

In addition to central nervous system development, TH is also required for auditory system development. AHDS patients are reported to respond to sound stimuli, but a characterization of hearing has not been described. Considering this, we investigated cochlear development and auditory function in single Mct8 and Oatp1c1 knockout mice as well as Mct8 and Oatp1c1 double knockout mice to gain insight on auditory function in AHDS patients. Using histological analysis, we quantified the area of the tectorial membrane, greater epithelial ridge, and tunnel of Corti (cochlear targets of TH) at postnatal day 7 and 15. To assesses auditory function, auditory‐evoked brainstem (ABR) responses were analyzed. Histological analysis demonstrated no significant difference in the size of the tectorial membrane, tunnel of Corti, or greater epithelial ridge. ABR data demonstrated that Mct8 and Oatp1c1 double KO mice, as compared to wildtype, had significantly elevated hearing thresholds at 32kHz, but not at 8kHz or 16kHz. Furthermore, analysis of ABR waveforms demonstrated significantly slower latencies at all sound frequencies. Taken together, these results suggest that cochlear anatomy during early postnatal development is largely normal in Mct8 and Oatp1c1 double KO mice, but processing of the auditory signal through the brainstem is altered. Ongoing studies are investigating whether the delayed processing is a result of altered myelination of the auditory pathway.

ORAL 23

Thyroid Hormone Action Metabolism and Regulation Basic Oral

DISRUPTION OF T3‐INDUCED EPIGENETIC REGULATOR MBD3 LEADS TO GROWTH INHIBITION AND DEVELOPMENT RETARDATION IN XENOPUS

Liezhen Fu*, Shouhong Wang, Yun‐Bo Shi

National Institutes of Health, USA

Adult organ‐specific stem cells are critical for organ homeostasis as well as tissue repair and regeneration. However, it has been difficult to study the formation of adult stem cells during vertebrate development. The development of adult intestine during thyroid hormone (T3)‐dependent frog metamorphosis, which involves apoptotic degeneration of the larval epithelium and de novo formation of adult stem cells, offers a unique opportunity to study adult stem cell development. T3 controls frog metamorphosis through T3 receptor (TR)‐mediated regulation of T3 response genes. To identify direct T3 response genes, we previously carried out a ChIP (chromatin immunoprecipitation)‐on‐chip analysis with a polyclonal anti‐TR antibody on the tadpole intestine and identified many putative TR target genes. Among them is the methyl‐CpG binding domain protein 3 (MBD3) gene, which has been implicated to play important roles in epigenetic regulation of cellular processes as a subunit of the Mi‐2/NuRD (Nucleosome Remodeling Deacetylase) complex. We showed that MBD3 is upregulated in the intestine by T3 and its expression peaks at stage 62, the climax of metamorphosis. We further showed that a putative TRE within the first intron of the MBD3 gene binds to TR/RXR in vitro and in vivo, and mediates T3 regulation of the MBD3 promoter in vivo. To investigate how MBD3 functions to regulate cell fate during intestinal metamorphosis, we successfully generated, through CRISPR/Cas9‐mediated genome editing, a germline mutant of 8nt‐deletion within the Xenopus tropicalis MBD3 coding sequence to knockout MBD3 (MBD3‐KO). Preliminary data suggested that homozygous MBD3‐KO significantly impeded tadpole growth and development, and delayed the onset of metamorphic climax, while knockout of only one copy of MBD3 gene (heterozygous MBD3‐KO) didn't significantly impact tadpole growth and development or change the time course of metamorphosis. Further studies are under way to investigate the impact of complete MBD3‐KO on the entire metamorphic process and tissue‐specific metamorphic changes, including intestinal remodeling and adult stem cell formation, and the underline molecular mechanisms.

ORAL 24

Thyroid Hormone Action Metabolism and Regulation Basic Oral

INTO THE UNKNOWN: THE ACTIONS OF THYROID HORMONE IN THE ZONA INCERTA

Julia Maier*¹, Riccardo Dore¹, Mehdi Pedaran¹, Anna Lena Cremer², Heiko Backes², Jens Mittag¹

¹Institute for Endocrinology and Diabetes, Molecular Endocrinology, University of Lübeck, Germany,²Max‐Planck‐Institute for Metabolism Research, Multimodal Imaging of Brain Metabolism, Germany

The ability of thyroid hormones (TH) to regulate body temperature is well established. While the active hormone T3 can act peripherally to induce thermogenesis in fat and muscle, it also acts centrally in the brain to increase body temperature through the sympathetic nervous system. Most remarkably, recent studies show that T3 treatment in mice causes an elevated body temperature even at 10°C, far below thermoneutrality, suggesting that T3 is altering the body temperature set point and causing a state of pyrexia rather than hyperthermia. However, the precise neuroanatomical substrate for this action has remained unknown. To identify candidate brain regions, PET/CT scans of mice have been conducted, and show neuronal activation of the Zona Incerta (ZI), a brain region in the subthalamus, upon treatment with T3. This region has previously been indicated in the control of body temperature and in the modulation of anxiety. The objective of this study is to determine the role of the ZI TH signalling in body temperature control and anxiety. Inhibition of TH signalling in the ZI was achieved by stereotactic injection of an adeno‐associated virus expressing a dominant negative thyroid hormone receptor α1 into the ZI of wildtype mice. While this inhibition did not lower the core body temperature, it resulted in tendentially increased anxiety, as indicated by higher serum corticosterone levels, an increased R amplitude in ECG and differentially expressed glucocorticoid receptor target genes. Furthermore, this also caused diminished body weight gain without changes in food and water intake or energy expenditure, as well as increased body weight loss during fasting, potentially caused by stress. Specifically targeting the dopaminergic neurons in the ZI using Tyrosine Hydroxylase Cre mice did not elicit the same effects, showing that dopaminergic neurons are not responsible for the observed changes. Taken together, this preliminary data indicates that TH signalling in the ZI plays a role in anxiety and stress in mice, while having no effect on the control of body temperature.

POSTER 295

Autoimmunity Basic Poster

AUTOMATING THE TURBO TSI BIOASSAY USING THE INTEGRA ASSIST PLUS PIPETTING ROBOT

Hannah Kim*¹, Lynn Miao², Jeffery Houtz²

¹QuidelOrtho, USA,²QuidelOrtho, USA

Objective: A rapid homogeneous bioassay (Turbo TSI Bioassay) was developed for the quantitative detection of Thyroid Stimulating Immunoglobulins (TSIs) in the serum of AITD patients and results are reported as TSI concentrations in IU/L. This bioassay is performed at room temperature and can be completed within 60 minutes without cell culture, sample dilution and washing steps. The purpose of this study is to demonstrate an automated Turbo TSI Bioassay using the INTEGRA Assist Plus Pipetting Robot.

Methods: Programs are created using VIALAB Pipetting Automation Software and transferred to INTEGRA VOYAGER electronic pipette to perform the Turbo TSI Bioassay. One tube of each Turbo TSI cAMP Reagent, Turbo TSI standard panels, and Turbo TSI controls are thawed and equilibrated to room temperature. One freezer vial of the Turbo TSI cells is thawed, transferred into 5 mL of Turbo TSI cAMP reagent, and placed in a reagent Reservoir on the INTEGRA Pipetting Robot. TSI standards, Controls, and samples are placed in a 1.5‐2 mL tube rack on the INTEGRA Pipetting Robot. Using the developed program, 5 μL of each sample and 50 μL of the cell suspension are added to the plate automatically. The plate is read after incubating 60 minutes at room temperature by GloMax luminometer. Results are reported as IU/L calculated from a standard curve using a Turbo TSI Data Analysis Tool.

Results: The automated Turbo TSI Bioassay has a LoD and LoQ of 0.016 IU/L and 0.030 IU/L, respectively, which is consistent with the manual Turbo TSI Bioassay. By testing seven precision panels covering the dynamic range of the Turbo TSI standard curve, the repeatability of the automated Turbo TSI Bioassay is very consistent across calculated TSI concentrations (IU/L). The overall within‐laboratory precision is ≤15%CV for all samples which demonstrates that the assay can achieve acceptable precision over the assay measuring range. The clinical sensitivity and specificity of the Turbo TSI Bioassay performed using INTEGRA Assist Plus pipetting robot was evaluated by testing 173 clinical serum samples in comparison with the original data generated manually by Quest laboratory. Results show the positive and negative percent agreement between the manual Turbo TSI Bioassay and the automated Turbo TSI Bioassay were 90% and 99%, respectively.

Conclusions: The Turbo TSI Bioassay can be automated using INTEGRA Assist Plus Pipetting Robot to improve productivity, performance and reduce operator labor without affecting LoD, LoQ, sensitivity and repeatability.

POSTER 296

WITHDRAWN

POSTER 297

WITHDRAWN

POSTER 298

Autoimmunity Clinical Poster

A PROSPECTIVE, OBSERVATIONAL STUDY ON THE EFFECT OF AN ABLATIVE VS A CONSERVATIVE APPROACH FOR THE TREATMENT OF GRAVES' HYPERTHYROIDISM IN PATIENTS WITH MODERATE‐TO‐SEVERE, ACTIVE GRAVES' ORBITOPATHY

Giulia Lanzolla*^1,2, Giada Cosentino¹, Simone Comi¹, Francesca Menconi¹, Giovanna Rotondo Dottore¹, Maria Maglionico¹, Chiara Posarelli¹, Michele Figus¹, Rossella Elisei¹, Ferruccio Santini¹, Michele Marinò¹

¹University of Pisa, Italy,²University of Pennsylvania, USA

Objectives: Optimal treatment for Graves' hyperthyroidism (GH) in patients with moderate‐to‐severe, active Graves' orbitopathy (GO) remains to be established. There is debate on whether a conservative (antithyroid drugs, ATDs) or an ablative approach (radioactive iodine, RAI, or surgery, Tx) has to be preferred. The aim of the present study was to investigate whether these different approaches result in a different outcome of GO following intravenous glucocorticoids (ivGCs).

Methods: The study design entailed enrollment of 52 consecutive patients with recent onset (≤18 mo.) GH and moderate‐to‐severe, active GO. Following adequate counseling, patients freely choose between an ablative (RAI for ultrasound thyroid volume ≤30 ml, Tx for volume >30 ml) or a conservative approach, to be then treated with ivGCs (12 weekly infusions of methylprednisolone; cumulative dose: 4.5 g). Primary outcome was the overall outcome of GO at 24 weeks (composite evaluation). Secondary outcomes were: 1) outcome of single eye features: 2) quality of life (GO‐QoL); 3) GO worsening at 24 weeks.

Results: Of 52 patients enrolled, 48 completed the 24‐week evaluation, 23 in ablation group (22 treated with RAI and one with Tx), and 25 in ATDs. The two groups did not differ for baseline parameters (sex, age, smoking habits, BMI, thyroid volume, thyroid function, LDL‐cholesterol, GO features, TSH‐receptor autoantibodies, and GO‐QoL). The proportion of overall GO responders at 24 weeks was greater in ablation group (47.8% vs 16% in ATDs; OR 4.81; 95% CI from 1.25 to 18.5; P = 0.028). There was a trend to a greater proportion of proptosis, clinical activity score (CAS), eye duction, and GO‐QoL responders in ablation group, although the difference did not reach significance. Only one patient (4.3%) worsened in ablation group compared with 3 (12%) in ATDs, with no statistical difference. Forty‐eight mild adverse events (20 in ablation and 28 in ATDs group) in 36 patients (16 in ablation and 20 in ATDs group) were recorded, with no difference between groups.

Conclusions: An ablative approach for GH treatment resulted in a better overall outcome of GO following ivGCs. Further, randomized clinical trials are needed to confirm our observations.

POSTER 299

Autoimmunity Clinical Poster

INTEGRATIVE ANALYSIS OF GUT MICROBIOTA AND FECAL METABOLITES IN EUTHYROID PATIENTS WITH AUTOIMMUNE THYROIDITIS IN THE FIRST TRIMESTER OF PREGNANCY

Kan Chen*, Zhenyu Lin, Jinjia Zhang, Yiyang Gao, Zhongyan Shan, Weiping Teng, Jing Li

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, China

Objective: Autoimmune thyroiditis (AIT) is a common autoimmune endocrine disorder, characterized by increased serum autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb). AIT is frequently found in women of childbearing age and strongly linked to adverse pregnancy outcomes like miscarriage. Our study investigates the differences in gut microbiota and fecal metabolites between euthyroid AIT and healthy pregnant women in the first trimester, and the interconnections between them.

Methods: We examined gut microbiota composition differences in 26 euthyroid AIT patients and 30 healthy pregnant women during the first trimester using 16S rDNA gene amplification and sequencing analysis. We also characterized fecal metabolomics profiles with ultrahigh‐performance liquid chromatography–mass spectrometry. Furthermore, we analyzed the associations between gut microbiota and fecal metabolomics to elucidate meaningful correlations.

Results: We identified significant gut microbiota composition differences between euthyroid AIT patients and healthy pregnant women in the first trimester. LEfSe analysis revealed that the abundance of Rhodospirillales, Rhodospirillaceae, Peptococcus, Peptococcaceae 1, and Clostridiales_Incertae Sedis XI were significantly increased, while Coprobacter abundance was significantly decreased in euthyroid AIT patients compared to healthy pregnant women in the first trimester. Fecal metabolomics analysis revealed unique metabolic characteristics in euthyroid AIT patients compared to healthy pregnant women in the first trimester. KEGG enrichment analysis indicated differential fecal metabolites primarily participated in Arachidonic acid metabolism, Serotonergic synapse, alpha‐Linolenic acid metabolism, and Bile secretion pathways. In addition, there was a correlation between gut microbiota and fecal metabolites in euthyroid AIT patients in the first trimester. Among them, Peptococcus abundance was positively correlated with Sulfoacetic acid and 7‐(3,4‐dihydroxyphenyl)‐5‐hydroxy‐1‐(4‐hydroxyphenyl)heptan‐3‐one levels in the positive ion mode and negatively correlated with 7‐Methylxanthine and 3‐Hydroxypicolinic acid levels in the negative ion mode. Coprobacter abundance was negatively correlated with Cadaverine levels in the positive ion mode and negatively correlated with Caprylic acid and 3‐amino‐1H‐pyrazolo[4,3‐c]pyridine‐4,6‐dio levels in the negative ion mode.

Conclusions: During the first trimester, euthyroid AIT disrupts gut microbiota composition and impacts fecal metabolic balance. Regulation of gut microbiota and fecal metabolites may prevent and treat adverse early pregnancy outcomes or complications, providing new strategies and targets for adverse early pregnancy outcomes and complications associated with AIT.

POSTER 300

Autoimmunity Clinical Poster

UPDATE ON SELENIUM AND AUTOIMMUNE THYROID DISEASES

Hassan Heshmati*¹, Vahab Fatourechi²

¹Endocrinology Metabolism Consulting, LLC, USA,²Mayo Clinic, USA

Objective: Selenium is a trace element essential for life. It is critical for the function of thyroid gland. Studies have suggested that selenium may be involved in the pathogenesis of several thyroid disorders. This review presents an update on the role of selenium in autoimmune thyroid diseases.

Methods: A systematic search of literature was conducted using the search terms selenium, thyroid function, autoimmunity, Hashimoto's thyroiditis, Graves' disease, and Graves' ophthalmopathy.

Results: Selenium is present in specific selenoproteins (e.g., glutathione peroxidase, thioredoxin reductase, and iodothyronine deiodinase) as selenocysteine. Selenoproteins have multiple biological functions including antioxidant activities. They are involved in the regulation of immune system and thyroid hormone metabolism. The thyroid gland is an organ with the highest concentration of selenium. The main environmental and dietary sources of selenium are water, nuts, cereals, eggs, meat, and fish. There is a high variability in the intake of selenium around the world. The recommended daily intake is 55‐75 μg/day. The range of optimal serum levels of selenium is 90‐120 μg/L. It is estimated that at least 15% of the world population has selenium deficiency. Autoimmune thyroid diseases are represented predominantly by Hashimoto's thyroiditis and Graves' disease and affect up to 5% of the world population (mainly female subjects). Studies have reported that serum levels of selenium are lower in patients with Hashimoto's thyroiditis compared to healthy subjects and that selenium supplementation can decrease the levels of thyroid autoantibodies in patients with Hashimoto's thyroiditis. According to some studies, patients with newly diagnosed Graves' disease have lower serum levels of selenium compared to those in long‐term remission and selenium supplementation enhances the effect of antithyroid drugs and lowers the levels of TSH receptor antibodies in patients with Graves' disease. Selenium therapy also improves Graves' ophthalmopathy.

Discussion/Conclusion: Selenium is an essential trace element critical for thyroid function. Selenium deficiency may be a risk factor for the development of Hashimoto's thyroiditis and Graves' disease and selenium supplementation can be beneficial in these autoimmune conditions including Graves' ophthalmopathy. However, more controlled studies are needed before recommending routine selenium supplementation for the management of autoimmune thyroid diseases in guidelines.

POSTER 301

Autoimmunity Clinical Poster

IMPACT OF THYROID EYE DISEASE ON SPECIFIC ACTIVITIES MEASURED BY THE GRAVES' QUALITY OF LIFE QUESTIONNAIRE

Terry Smith¹, Sara Tanweer^2,3, Naina Barretto³, Robert Holt*³

¹Department of Ophthalmology and Visual Sciences and Department of Internal Medicine, Kellogg Eye Center‐Michigan Medicine and University of Michigan, USA,²2. Rosalind Franklin University, USA,³3. Horizon Therapeutics plc, USA

Objective: Connective tissue inflammation in thyroid eye disease (TED) can result in disutility due to proptosis and ocular muscle remodeling affecting vision. The Graves' ophthalmopathy quality of life (GO‐QOL) questionnaire assesses impact of TED on visual function and appearance. We assess how sex, age, and severity of diplopia and proptosis affected specific areas of QOL in untreated TED patients.

Method: GO‐QOL baseline data from two clinical trials of moderate‐severe, active TED patients were examined for the extent of visual and appearance functioning limitations in activities including reading, watching TV, hobby or pastime engagement, driving, ambulation, and appearance and social interactions, on a 3‐point scale: 1 = seriously/2 = a little/3 = not at all limited, or not applicable.

Responses were assessed in subgroups of men/women, <60/≥60 years, mild/severe diplopia (Severe: Gorman score 2/3 [inconstant/constant], Mild: score of 1/0 [intermittent/no diplopia]), and small/no proptosis or large proptosis (<3mm or ≥3mm).

Results: Data from 171 patients were included. For visual functioning, majority had some limitation in reading (74%), watching tv (67%), and driving (64%). High percentages of both men (N = 46) and women (N = 125) were hindered by TED (59% and 66%, respectively) and had limitation in reading and driving. No large differences were observed between patients <60 (N = 129) or ≥60 (N = 42). In mild diplopia (N = 97) vs severe diplopia (N = 74), differences were observed in reading (70% vs 78%) and driving (58% vs 71%).

A greater proportion of patients with large proptosis (N = 104) vs small/no proptosis (N = 67) were hindered by TED (69% vs 55%). Of 171 patients, 95% were affected by changes in appearance; 75% of women were very affected vs 50% of men. A larger proportion of patients <60 vs ≥60 years showed an impact on appearance‐related questions. A greater proportion of patients with large vs small/no proptosis (74% vs 60%) were very affected by appearance change.

Conclusion: A majority of patients with TED had some limitation in activities such as reading or driving, and most were affected by changes in appearance. Specific activities are more impacted in particular subgroups.

POSTER 302

Autoimmunity Clinical Poster

DISRUPTION OF TEPROTUMUMAB TREATMENT IN PATIENTS WITH THYROID EYE DISEASE (TED) IS ASSOCIATED WITH INCREASED RETREATMENT RATE

Raymond Douglas¹, Robert Holt*², Anahita Qashqai², Shoaib Ugradar³

¹1. Cedars–Sinai Medical Center, USA,²Horizon Therapeutics, plc, USA,³Private Practive, USA

Objective: Examine the effect of disrupted teprotumumab treatment course on retreatment with an additional course of teprotumumab.

Methods: Deidentified data (AllCare/IQVIA) of patients prescribed an additional course (retreatment) after receiving an initial full course of teprotumumab (8 infusions) up to 3/2022 were examined for TED‐related claims, number enrolled for retreatment, number of infusions and time between courses. Undisrupted patients and those with disruption (gap of >60 days between any consecutive infusions) were observed for 1 year after the initial full course of teprotumumab to assess retreatment rate. Chi‐square tests were used for significance.

Results: Of patients completing an undisrupted initial course of teprotumumab, significantly fewer [6.5% (279/4,230)] were prescribed an additional course within 1‐year post‐completion of their 8th infusion vs patients with a disruption between infusions [10.5% (122/1,155)], p < 0.0001. 96% (117/122) of patients had COVID‐related supply disruptions.

Similar demographics were observed between the two groups. Among undisrupted patients, 76% were female, mean age 57(13) years. Among the disrupted patients, 71% were female with mean age 57(11) years.

TED claims for undisrupted patients within 1 year before 1st course included proptosis (34%), diplopia (16%), lid retraction (13%), strabismus (7%), optic neuropathy (ON) (4%), and 4 with eye surgeries. Claims 1‐year post‐ 8th infusion included proptosis (15%), diplopia (11%), lid retraction (15%), strabismus (9%) ON (2%), and 7 with eye surgeries.

In the disrupted patients, claims analysis pre‐teprotumumab showed 17% proptosis,15% diplopia, 2% ON, and 1 surgery; claims 1 year after the 8th infusion included proptosis (22%), diplopia (9%), ON (1%), and 1 surgery.

Of patients starting the second course of teprotumumab, mean time between courses was 11(3) months for undisrupted, and 10(3) for disrupted patients.

Conclusion: Higher teprotumumab retreatment rate was observed in disrupted (10.5%) vs undisrupted (6.5%) patients (p < 0.0001). There was a significant difference (p < 0.02) in proptosis claims between the groups before retreatment with a 19% reduction in undisrupted versus a 5% increase in disrupted patients pre‐ to post‐teprotumumab treatment. Disrupting the recommended regimen of teprotumumab resulted in higher retreatment rates and a higher number of claims for proptosis. Additional research is needed.

POSTER 303

Autoimmunity Clinical Poster

EFFICACY OF RITUXIMAB COMBINED WITH ORBITAL RADIOTHERAPY IN INTRACTABLE AND ACTIVE THYROID EYE DISEASE

Yi Wang^1,2,3, Li Gu^1,2,3, Jun Jin^1,2,3, Yining Wei^1,2,3, Xuefei Song^1,2,3, Jing Sun^1,2,3, Yinwei Li^1,2,3, Wenyong Tu⁴, Xiulan Liu⁵, Ziyang Shao⁴, Huifang Zhou*^1,2,3

¹Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China,²Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, China,³Chinese Consortium for Thyroid Eye Disease (CCTED), China,⁴Department of Oral Maxillofacial‐Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China,⁵Department of radiotherapy, Fengcheng hospital, China

Objective: Thyroid eye disease (TED) is an autoimmune disease that is closely related to thyroid dysfunction. Intravenous glucocorticoids pulse therapy remains the first‐line treatment. However, the efficacy of glucocorticoids is only 60% and the proportion of refractory patients is high. This study aims to investigate the efficacy of orbital radiotherapy combined with rituximab in the treatment of TED patients refractory to glucocorticoids.

Methods: This study is designed as a retrospective cohort research, which involved 23 active and intractable TED patients who received orbital radiotherapy combined with rituximab treatment and 14 patients who were treated with orbital radiotherapy alone from August 2020 to October 2022. Clinical data including clinical activity score (CAS), exophthalmos, lid aperture, best corrected visual acuity (BCVA), thyrotropin receptor antibody (TRAb) level and diplopia score were collected before, 3 months after and 6 months after the treatment. The effect of the combinative therapy on the ocular manifestations and TRAb level was analyzed and compared to that of orbital radiotherapy alone.

Results: At 6 months after the combinative therapy, the treatment efficacy was 94.74%. And the proportion of active affected eyes was reduced from 91.30% to 7.89%. The average CAS was significantly reduced from 3.89 ± 1.27 to 1.16 ± 0.86 (P < 0.0001). The average BCVA was significantly improved from 4.61 ± 0.61 to 4.84 ± 0.48 (P = 0.0010). The average TRAb level was significantly reduced from 10.91 ± 10.13 IU/L to 3.83 ± 4.38 IU/L (P = 0.0227). Comparative analysis of clinical data at last visit indicated that the treatment efficacy of the combinative therapy group was 82.61% and higher than that of simple orbital radiotherapy group (57.14%). The average CAS reduction in the combinative therapy group was 2.30 ± 1.50 and significantly higher than that of simple orbital radiotherapy group (1.11 ± 1.57, P = 0.0017).

Conclusion: Orbital radiotherapy combined with rituximab is of excellent efficacy in intractable TED patients. It can lead to significant reduction of CAS and TRAb level, and improvement of visual acuity and diplopia. Compared to orbital radiotherapy alone, the combinative therapy has higher treatment efficacy and works better in reducing disease activity of TED.

POSTER 304

Autoimmunity Clinical Poster

CLINICAL CHARACTERISTICS OF AND RISK FACTORS FOR THYROID IMMUNE‐RELATED EVENTS FOLLOWING IMMUNE CHECKPOINT INHIBITOR TREATMENT

Xiaowen Zhang*, Xinlin Zhang

Affiliated Drum Tower Hospital, Nanjing University School of Medicine, China

Objective: To determine the clinical characteristics of thyroid immune‐related adverse events (Thy‐irAEs) and identify the risk factors for Thy‐irAEs.

Methods: Data of patients with malignant tumors treated with immune checkpoint inhibitors (ICIs) were retrospectively collected from the affiliated Drum Tower Hospital, Medical School of Nanjing University from January 1, 2018 to March 1, 2022. Thyroid function and anti‐thyroid antibodies were tested at baseline and at regular intervals after ICIs treatment.

Results: A total of 886 subjects were included in the study, among which 332 with lung cancer, 154 with gastric cancer, 70 with liver cancer, 60 with esophageal cancer. Thy‐irAEs were documented in 297 patients (33.5%) following a median follow‐up of 52 weeks. 82 (9.2%) had clinical hypothyroidism, 133 (15.0%) had subclinical hypothyroidism, 49 (5.5%) had clinical hyperthyroidism, and 33 (3.7%) had subclinical hyperthyroidism. Compared with patients without Thy‐irAEs, those with Thy‐irAEs were more likely to be female, showed higher baseline titers of TPOAb and TgAb, and higher thyroid stimulating hormone (TSH) levels. Positive baseline TgAb (adjusted odds ratio [OR] 5.02, P < 0.001) and TPOAb (OR 5.94, P < 0.001), increased baseline TSH (OR 1.15, P < 0.001), free triiodothyronine (OR 1.35, P = 0.001), and total cholesterol (OR 1.2, P = 0.016) were independent risk factors for Thy‐irAEs after ICIs treatment. There was no difference before and after treatment for patients with positive baseline TgAb and TPOAb. Compared with baseline, TgAb and TPOAb concentrations significantly increased following ICIs treatment, both among those positive (P = 0.018 and = 0.004 respectively) or negative (P < 0.001 and <0.001 respectively) for baseline antibody. 10% of patients negative for baseline antibody shifted to positive following Thy‐irAEs.

Conclusions: One third of patients receiving ICIs treatment developed Thy‐irAEs. Baseline TgAb/TPOAb, TSH, total cholesterol, and free triiodothyronine were risk factors for Thy‐irAEs after ICIs treatment. TgAb and TPOAb concentrations significantly increased following ICIs treatment, but only 10% of patients negative for baseline antibody shifted to positive.

POSTER 305

Disorders of Thyroid Function Basic Poster

RETROSPECTIVE EVALUATION OF GROWTH PARAMETERS IN CHILDREN DIAGNOSED AND TREATED WITH TRANSIENT AND PERMANENT CONGENITAL HYPOTHYROIDISM

Betul Ersoy*

Manisa Celal Bayar Universitesi, Turkey

Objective: Congenital hypothyroidism (CH) is the most common endocrinological problem in neonates. Since thyroid hormones are also important determinants of postnatal somatic growth, we compared the growth parameters of children with transient and permanent CH who received thyroid hormone replacement in this study.

Subjects and Methods: Between January 2000 and December 2012, 200 patients, 88 girls (44.0%) and 112 boys (56.0%) with a diagnosis of CH, who were referred to the pediatric endocrinology outpatient clinic were included in the study. The patients were given levathyroxine, and it was discontinued at the age of 3 for 3 weeks. Permanent CH (PCH) was diagnosed if the thyroid‐stimulating hormone(TSH) level was above >10.0 μU/ml, and treatment was restarted. If TSH did not increase, transient CH (TCH) was diagnosed. At the time of diagnosis and at the last follow‐up date, growth parameters, growth rates, and the time for TSH values to fall below 10 and 5 μU/ml were recorded. Standard deviation score (SDS) was calculated for anthropometric parameters.

Results: PCH in 51.5% of patients, TCH in 48.5% was diagnosed. PCH was more common in girls than boys (56.8% versus 47.3%). The duration of TSH levels <10 and <5 with treatment was found to be significantly higher in patients with PCH than those with TCH. SH levels <10 μU/ml and <5 μU/ml with treatment was found to be significantly higher in patients with PCH than those with TCH (p = 0.039 and p = 0.016, respectively). The growth parameters at diagnosis and the last follow‐up of the patients did not differ significantly except for weight for height (W/H). W/H in patients PCH was significantly higher than the others (p < 0.001). Although the annual growth rate was significantly lower in patients PCH (p = 0.014), it was not different in SDS.

Conclusion: The growth parameters of children with PCH and TCH were similar both at diagnosis and during treatment, except for W/H and annual growth rate. The low annual growth rate in children with PCH may result in W/H. The earlier normalization of TSH levels with treatment in infants diagnosed with CD suggests that the infant may have TCH.

POSTER 306

Disorders of Thyroid Function Case Study Poster

CARDIAC TAMPONADE: A RARE INITIAL PRESENTATION OF HYPOTHYROIDISM

Kavya Nalluri*, Ceyda Akartuna, Amin Sabet

St Elizabeth's Medical Center, Boston University School of Medicine, USA

Introduction: Hypothyroidism is a very common disorder with an estimated prevalence among adults of up to 10% for subclinical disease and up to 2% for overt hypothyroidism. The principle cardiovascular manifestations of overt hypothyroidism include an increase in peripheral vascular resistance contributing to hypertension, a decrease in cardiac contractility, and bradycardia. Pericardial effusions are another well‐described and relatively common manifestation of severe hypothyroidism that are usually hemodynamically insignificant and do not require intervention other than thyroid hormone replacement. The initial presentation of cardiac tamponade requiring pericardiocentesis is an exceedingly rare occurrence.

Description of Case: We describe a 21‐year‐old male with no known past medical history who presented to the emergency department complaining of severe abdominal pain radiating to his right chest with associated dizziness and was found to have a large pericardial effusion on CT scan of the abdomen and pelvis. Echocardiography confirmed the presence of cardiac tamponade. Left ventricular contractility was noted to be normal. The patient underwent urgent pericardiocentesis. Subsequent investigation revealed severe hypothyroidism with a TSH level >600 milliunits per liter (mU/l) and undetectable free T4. On further questioning, the patient reported a four‐year history of progressive fatigue as well as significant weight gain. The patient had complete resolution of his abdominal and right chest discomfort following the pericardiocentesis. He was treated with levothyroxine and did not have reaccumulation of pericardial fluid on subsequent echocardiography.

Discussion: Our patient presented with an uncommon initial manifestation of hypothyroidism, pericardial effusion causing cardiac tamponade. This case highlights the need to consider hypothyroidism as a potential cause of pericardial effusion with tamponade. It further demonstrates that the development of pericardial effusion with tamponade may precede the development of a dilated cardiomyopathy with reduced cardiac contractility in patients with severe hypothyroidism. Lastly, we note that our patient did not present with tachycardia or hypotension, two common findings in cardiac tamponade, and speculate that these signs may have been masked by the effects of severe hypothyroidism on cardiac chronotropy and systemic vascular resistance.

POSTER 307

Disorders of Thyroid Function Case Study Poster

CHALLENGES IN THE MANAGEMENT OF GRAVES' DISEASE COINCIDING WITH AML

Rehan Razzaq*, Grace Prince, Sarasi Jayaratne

VCU Health System, USA

Introduction: Graves' disease is the most common cause of hyperthyroidism among adults and is traditionally treated with thionamides, radioactive iodine (RAI) or total thyroidectomy. However, literature guiding the treatment of individuals requiring treatment for Graves' disease with concurrent chemotherapy is limited. This case report describes the challenges associated with the treatment of Graves' disease in an individual newly diagnosed with acute myeloid leukemia (AML).

Description of the Case

A 68 y.o. male with PMHx of HS, untreated hyperthyroidism, and new onset atrial fibrillation presented with several weeks of 40 pound weight loss, weakness, shortness of breath, palpitations, and blurred vision. He was subsequently diagnosed with AML and was found to have hyperthyroidism secondary to Graves' disease (undetectable TSH, elevated T3 and FT4, and positive TRAB) complicated by atrial fibrillation. He was started on propanolol and low dose methimazole (5 mg) despite the known risk of agranulocytosis, as RAI and thyroidectomy were felt to carry greater comparative risks in the setting of AML. Shortly thereafter, the patient started induction chemotherapy.

Methimazole was discontinued in the presence of anticipated neutropenia, however it was restarted at a lower dose with the addition of cholestyramine due to worsening hyperthyroidism and in anticipation of count recovery. Unfortunately, methimazole was again discontinued due to worsening, conjugated hyperbilirubinemia presumed secondary to drug‐induced liver injury (DILI). With persistent hyperthyroidism, the patient was transitioned to hydrocortisone with continued use of cholestyramine and propranolol. Repeat labs within 4 days of initiation of steroids showed normal peripheral hormones.

Discussion: Our patient's treatment was ultimately limited by DILI, and case reports have detailed that methimazole may have enhanced hepatotoxicity with underlying conditions such as a malignancy. This complex case illustrates the tremendous importance of assessing the anticipated risks and benefits and understanding the unique limitations of treatment in a patient with Graves' disease requiring cytotoxic chemotherapy for AML. We highlight the importance of strict lab monitoring and consideration of second and third‐line therapies in these cases.

POSTER 308

Disorders of Thyroid Function Case Study Poster

A CASE OF MALIGNANCY‐ASSOCIATED HYPERTHYROIDISM DUE TO A LARGE FACIAL BASAL CELL CARCINOMA

Arya May*, Mouna Gunda, Amy Warriner

University of Alabama Birmingham, USA

Introduction: Based on literature review, the highest rates of metastases to the thyroid from primary malignancies include: renal cell carcinoma 48%, colorectal 10%, lung 8%, and breast cancer 8%. Excluding patients with preexisting thyroid disease, patients with thyroid metastases are usually euthyroid, with only occasional hypothyroidism and, rarely, hyperthyroidism. This case examines a case of hyperthyroidism associated with a large, local, neglected basal cell carcinoma.

Description of the case

A 61‐year‐old female with no prior medical history complains of nausea and generalized weakness with a slow‐growing left facial mass. She reports 50 pounds of weight loss over the last six months. She has been neglecting the ulcerated left‐sided facial mass for ten years. Her exam reveals an 18 cm x 9 cm mass at the left posterior skull, extending to the left cheek with the involution of her left ear. CT head and neck uncover destruction of facial bones and skull base. Thyroid gland is severely enlarged with bilateral masses. Thyroid labs include undetectable TSH and elevated free T4 (fT4) 2.34 ng/dL (0.58‐ 1.64ng/dL). Free T3 4.4 pg/mL (2.8‐ 4.4 pg/mL). She has no history suggestive of thyroid disease. Therefore, no thionamide medications were started. Anti‐TPO, TRAB, and anti‐thyroglobulin antibodies are negative. Biopsy revealed basal cell carcinoma. The mass is inoperable, thus, the focus of her treatment shifted to supportive care. She remains clinically euthyroid, with normalization of fT4 but persistently suppressed TSH.

Discussion: Due to the presentation, symptoms, and notable thyroid masses, our leading diagnosis is destructive thyroiditis. The mechanism of destructive thyroiditis mirrors subacute thyroiditis, with damage to the thyroid tissue resulting in a surge of thyroxine. In both disease states, the duration and extent of injury are limited to the underlying process. In malignancy‐associated hyperthyroidism, thyroid gland recovery may be linked to treatment and control, whereas hypothyroidism is likely if the malignancy progresses. As such, thyroid function changes can be a prognostic indicator. To our knowledge, basal cell carcinoma has not been previously known to metastasize to the thyroid. More research into possible malignancy‐specific causes of destructive thyroiditis is warranted.

POSTER 309

Disorders of Thyroid Function Case Study Poster

WHEN ALL ELSE FAILS – A CASE OF AMIODARONE INDUCED THYROTOXICOSIS TREATED WITH SINGLE PASS ALBUMIN DIALYSIS

Dmitriy Stasishin*¹, Sheetal Bulchandani¹, Farah Kitana², Meeta Sharma³

¹Georgetown/ Washington Hospital Endocrinology Program Medstar, USA,²Washington Hospital Center Internal Medicine Program, USA,³Washington Hospital Center department of Endocrinology, USA

Introduction: Thyroid storm is a potentially fatal condition requiring intensive care and treatment. Single Pass Albumin Dialysis (SPAD) is a highly effective, but underutilized tool in the treatment of severe symptomatic thyrotoxicosis and states such as thyroid storm. The mechanism of action is well defined by thyroid hormone's binding affinity to albumin and was first reported as a treatment for thyroid storm by Kotball et al (1). However, this technique continues to be underutilized for this indication.

We present a case of a patient with new onset refractory Amiodarone Induced Thyrotoxicosis (AIT) precipitating thyroid storm, who was treated with SPAD.

Case: 74‐year‐old male with a past medical history of coronary artery disease, ischemic cardiomyopathy, and chronic kidney disease was brought to the emergency department for shortness of breath and bilateral lower extremity swelling. He had been on amiodarone therapy for months. Labs on presentation demonstrated an undetectable thyroid stimulating hormone level and free thyroxine level of 9.68ng/dl. Further labs demonstrated a total triiodothyronine level of 309.5ng/dl. The patient was treated with maximal medical therapy including oral methimazole (120mg/day), intravenous hydrocortisone (300mg/day), Lugol's Iodine, and Cholestyramine.

Despite this he had poor response to therapy as evidenced by a slow decrease in free thyroxine levels decreasing from 10ngl/dl to 8.5ngl/dl. He developed a non‐fatal cardiac arrest due to ventricular tachycardia.

Given his refractory thyroid storm we performed SPAD daily for 5 days. Free thyroxine levels responded by decreasing over 50% from 8.5 ng/dl to 3.36 ng/dl. The patient had improvement in symptoms as well. However due to the protracted course of his thyroid storm and advanced ischemic cardiac disease eventually developed cardiogenic shock and passed away.

Discussion: Severe thyrotoxicosis and thyroid storm refractory to medical therapy are indications for advanced treatment mechanisms such as SPAD. We would like to express in our opinion that SPAD continues to be a highly effective methodology and that it should be utilized more frequently and earlier to limit and avoid morbidity and mortality subsequent to thyroid storm.

POSTER 310

Disorders of Thyroid Function Clinical Poster

EXPLORING THE ASSOCIATION BETWEEN THYROID FUNCTION AND ORAL MICROBIOME DIVERSITY: AN NHANES ANALYSIS

Liang Zheng*¹, Jiajun Luo²

¹The First Affiliated Hospital of Sun Yat‐sen University, China,²The University of Chicago, USA

Background: Thyroid function is an essential component of human metabolic activities. Oral microbiome is a crucial indicator for oral and general health. However, few studies have investigated the association between thyroid functions and oral microbiome.

Objective: To investigate the association between thyroid functions and oral microbiome diversity.

Method: Data on thyroid functions and the oral microbiome in the US National Health and Nutrition Examination Survey (NHANES; 2009–2012) were analyzed. Thyroid functions were defined using thyroid hormones and related biomarkers. Oral microbiome was measured using the observed number of amplicon sequence variants (ASVs) and the Bray‐Curtis dissimilarity. Linear regression was used to estimate the linear coefficient (β) and 95% confidence interval (CI) for the number of ASVs against thyroid functions, adjusted for sociodemographic variables, health conditions, and periodontitis. Non‐metric multidimensional scaling (NMDS) was used to analyze the Bray‐Curtis dissimilarity.

Results: A total of 2943 participants were analyzed. The observed number of ASVs has a weighted mean of 128.9. Self‐reported thyroid disease was associated with reduced number of ASVs (β = ‐9.5, 95% CI: ‐17.4, ‐1.6), if not adjusted for periodontitis. In the fully adjusted model, compared to normal thyroid function, both subclinical and clinical hyperthyroidisms were associated with reduced number of ASVs (β = ‐62.1, 95% CI: ‐76.2, ‐48.2; β = ‐29.4, 95% CI: ‐54.6, ‐4.3), respectively). Thyroid peroxidase antibodies higher than the reference range was associated with higher ASV number (β = 8.9, 95% CI: 1.1, 16.7). NMDS analysis suggested significant difference in oral microbiome composition between free triiodothyronine groups (p = 0.002), between free thyroxine groups (p = 0.015), and between thyroglobulin groups (p = 0.035).

Conclusion: Hyperthyroidism was associated with reduced oral microbiome diversity. Free triiodothyronine, free thyroxine, and thyroglobulin levels may alter the oral microbiome composition.

POSTER 311

Disorders of Thyroid Function Clinical Poster

WEIGHT GAIN AFTER RADIOIODINE TREATMENT FOR GRAVES ´DISEASE

Marcus Souza¹, Nicolau Lima¹, Tomoco Watanabe², Suemi marui*¹

¹Thyroid Unit, Endocrinology and Metabolism Divison, Hospital das Clinicas ‐ Faculdade de Medicina ‐ Universidade de Sao Paulo, Brazil,²Nuclear Medicine Divison, Hospital das Clinicas ‐ Faculdade de Medicina ‐ Universidade de Sao PauloHospital das Clinicas, Brazil

Introduction: Radioiodine therapy (RIT) is a safe and effective treatment for hyperthyroidism, especially in patients with Graves' disease (GD). However, it can cause weight gain often attributed to poorly controlled hypothyroidism.

Objective: To evaluate clinical and laboratory data associated with weight gain in patients undergoing RIT for hyperthyroidism.

Methods: Patients with hyperthyroidism due to GD were prospectively evaluated in a tertiary hospital from 2019 to 2022, before and 12 months after RIT. Thyroid function and autoimmunity were assessed using commercial assays immediately before, 3 and 12 months after RIT. Thyroid ultrasound and scintigraphy were performed by the Radiology Service with calculation of the dose of ¹³¹I administered.

Results: Weight and body mass index (BMI, kg/m²) were assessed in 115 patients with GD. The mean age at RIT was 47.9 ± 12.6 years, the majority being female (78%) and self‐declared caucasian (67%). Mean RIT absorbed dose was 542 ± 382 Gy. Successful was attained in 89% of cases, with the majority developed hypothyroidism. Before RIT, 4.4% of the cases were underweight, 32.2% with normal BMI, 39.1% overweight and 24.3% obese. Twelve months after the RIT, there was an increment in weight (kg) and percentage of weght gain of 5.6 ± 6.8 kg and 8.8 ± 11.3%, respectively, with a significant increase in cases classified as obese (40%) and overweight (36.5%). Increase in BMI occurred in 83%, achieving more than 10% of increment compared to pre‐treatment in 52% of treated cases. Patients with an increase in BMI one year after RIT (n = 95) compared to patients who maintained or reduced their BMI (n = 20) had higher pre‐RIT T3 concentrations (331 ± 188 and 222 ± 129 ng/mL, p = 0.018, respectively, normal range 80‐200 ng/dL) and lower concentrations of free T4 at 3 months after RIT (0.76 ± 0.68 and 1.49 ± 1.70 ng/dL, p = 0.003, respectively, normal range 0.93‐1.70 ng/dL). Weight gain and BMI were not associated with patients who presented with hypothyroidism even on levothyroxine or patients with euthyroid status (p > 0.05) after 1 year of RIT.

Discussion/Conclusion: Weight gain and higher BMI were frequent in patients with GD who underwent RIT. Higher previous hyperthyroidism and hypothyroidism at 3 months after RIT were associated with excessive weight gain at long term. Therefore, earlier attention on thyroid function must be taken to avoid weight gain, independently of thyroid status later after RIT success.

POSTER 312

Disorders of Thyroid Function Clinical Poster

IS COVID‐19 IMMUNIZATION OR INFECTION ASSOCIATED WITH THYROIDITIS? A LARGE POPULATION‐BASED STUDY

Hadar Duskin‐Bitan¹, Alon Peretz², Alex Gorshtein³, Tanya Beckenstein⁴, Doron Netzer⁴, Arnon D Cohen⁵, Walid Saliba⁶, Ilan Shimon³, Eyal Robenshtok*³

¹Rabin Medical Center and Clalit Health Services, Israel,²Clalit Health Services, Israel,³Endocrinology, Rabin Medical Center, Israel,⁴Community Medical Services Division, Israel,⁵Clalit Health Services, Israel,⁶Department of Community Medicine and Epidemiology, Technion‐Israel Institute of Technology, Israel

Introduction: COVID‐19 infection and immunizations have been implicated in the development of a range of autoimmune diseases, including thyroiditis. However, published data is limited, and based mostly on case reports.

Objective: To evaluate the association between COVID‐19 infection and/or BNT162b2 mRNA Pfizer COVID 19 vaccination with thyroiditis.

Material and methods: A population of 3,075,646 adults from the Clalit Health Services (CHS) were evaluated from March 2020 to September 2022. Patients with a new diagnosis of thyroiditis were identified, and matched (by age, sex and index date) in a 1:10 ratio to a control group. Exclusion criteria included prior treatment with levothyroxine, anti‐thyroid drugs, amiodarone, anti‐neoplastic drugs, and pregnancy. Multivariable conditional logistic regression models were used to evaluate the association between COVID‐19 infection, vaccines and thyroiditis.

Results: Three thousand eight‐hundred and ninety two new cases of thyroiditis were identified; of them 671 were excluded. The remaining 3,221 thyroiditis cases were matched with 32,210 controls. Rates of BNT162b2 mRNA vaccination (first, second or third dose) and COVID‐10 infection were evaluated prior to thyroiditis date (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days time points (p = 0.880/0.335/0. 174 respectively). No difference was found between groups in relation to COVID‐19 infection at these time points (p = 0.735/0.362/0.956 respectively). There was higher use of medications for the treatment of thyroiditis, including NSAIDS (28.6% vs. 7.9%, p < 0.01), steroids (10.3% vs. 1.8%, p < 0.01), and beta‐blockers (18.3% vs. 5.4%, p < 0.01).

Conclusion: Based on this large population study, no association was found between COVID‐19 infection and/or the BNT162b2 mRNA vaccine and thyroiditis.

POSTER 313

Disorders of Thyroid Function Clinical Poster

WHO PRESCRIBES LIOTHYRONINE AND THYROID EXTRACT? AN ANALYSIS OF THE MEPS DATABASE FROM 2013‐2020

Gustavo Penna*^1,2, Antonio Bianco¹, Matthew Ettleson¹

¹University of Chicago, USA,²Universidade Federal de Minas Gerais, USA

Introduction: A significant minority of patients with hypothyroidism remain dissatisfied with treatment with levothyroxine (LT4). This may lead patients and clinicians to explore alternative therapies, including liothyronine (LT3) and desiccated thyroid extract (DTE). Our study aimed to determine the specialties and providers who prescribe these medications and the context in which prescriptions are made.

Objective: To determine differences in provider type, provider specialty, and reason for visits between those outpatient encounters during which LT4, LT3, or DTE were prescribed.

Materials and Methods: This cross‐sectional study included 4,589 prescriptions for LT4, LT3, or DTE made for US residents aged over 18 years (excluding one patient under 18 years old) between 2013 ‐ 2020. Data was collected from the Medical Expenditure Panel Survey (MEPS). There were two group analyzed: 1)participants with at least one thyroid hormone prescription that was associated with an outpatient visit during the study period, 2) a subset of group 1 of those who reported having hypothyroidism or thyroid cancer in the survey. Outcomes included provider type associated with the visit, the specialty of the provider (if MD provider), and the reason for visit. As these are categorical outcomes, Chi square tests of association were utilized to compare differences.

Results: In the first group of 4,589 prescriptions analyzed, 93% were for LT4, 92 were for LT3, and 5% were for DTE. Significant associations (p < 0.001) were observed between the type of medication prescribed and the specialty, provider, and context of the visit in which the prescription was made. DTE and LT3 were commonly prescribed by non‐MD providers vs LT4. LT3 prescriptions were more commonly associated with psychiatry visits (8.7%). DTE prescriptions were more likely to be prescribed by alternative medicine providers (9.2%), nurse practitioners (7%), and other providers (7%). When group 2 was analyzed, the total number of prescriptions decreased from 4,589 to 3,563 (77%), with a loss of 82% of DTE prescriptions, 45% of LT3 prescriptions, and 19% of LT4 prescriptions. Significant associations (p < 0.001) were maintained between the type of medication prescribed and the specialty and context of the visit, but not for the provider (p < 0.061).

Conclusion: Prescriptions for LT3 and DTE for the treatment of hypothyroidism in the US are not uncommon, and non‐MD providers are more likely to prescribe them. DTE prescriptions were associated with alternative medicine visits, and further studies are necessary to investigate the differences in the number of prescriptions between the two analyzed groups.

POSTER 314

Disorders of Thyroid Function Clinical Poster

EFFECTS OF IODINE NUTRITIONAL STATUS CHANGE ON THYROID FUNCTION IN THE ELDERLY IN EXCESSIVE IODINE AREA OF JIANGSU PROVINCE: A SERIAL CROSS‐SECTIONAL STUDY OF SURVEYS

Mengjie Zhang¹, Yu Sun², Shuhang Xu*¹, Chao Liu¹

¹Nanjing University of Chinese Medicine, China,²XuZhou Medical University, China

Objective: To investigate the changes of iodine nutritional status and its effect on thyroid function in the elderly aged ≥65 years after water improvement in areas with high iodine concentration in drinking water.

Method: Data from the national epidemiological survey of thyroid disease, iodine nutrition, and diabetes (TIDE) in 31 provinces and municipalities of China from 2015 to 2017 were obtained from the Yaojing town of Xuzhou, Jiangsu (a water‐borne high iodine area). From May to August 2021, cluster sampling was used to select the elderly aged ≥65 years in Shunhe town, Suqian, Jiangsu province (the area with more than adequate iodine nutrition) and Yaoji town, Xuzhou (areas with high iodine concentration in drinking water). A total of 2717 subjects aged ≥65 years were included, including group 1, 258 subjects in TIDE study; Group 2, 1313 subjects in Xuzhou area; Group 3, 1146 subjects in Suqian area. To investigate the changes of iodine nutritional status and its effect on thyroid function in the elderly aged ≥65 years after water improvement in areas with high iodine concentration in drinking water.

Results: The urinary iodine concentration (UIC) in group 2 was significantly lower than that in group 1, and the difference was obvious (491.58 ± 384.93μg/L vs. 235.16 ± 67.09μg/L, P = 0.000), but there was no significant difference with group 3 (235.16 ± 67.09μg/L vs. 231.62 ± 66.11μg/L, P > 0.050). The serum TSH level in group 2 was significantly lower than that in group 1 (4.15 ± 9.19mU/L vs. 2.92 ± 5.14mU/L, P = 0.000). Compared with groups 2 and 3, the prevalence of subclinical hypothyroidism (Shypo) in the elderly in group 1 was the highest (22.48% vs. 10.13% vs. 8.12%, P = 0.000). TSH levels were linearly correlated with age in both excessive iodine and adequate iodine areas. TSH levels gradually increase with age. Among the younger old people (65‐74 years old), the prevalence rates of hypothyroidism in group 1, group 2 and group 3 were 18.68%, 11.02% and 6.71%, respectively, with significant statistical differences. Among the elderly (≥75 years old), only a statistically significant difference was found in the prevalence of hypothyroidism between group 1 and group 2, which were 36.84% and 12.29%, respectively.

Conclusion: Aging and iodine status are significantly related to the change of TSH level in the elderly. The prevalence of Shypo in the elderly can be significantly reduced after the iodine nutrition status of the elderly is restored to normal.

POSTER 315

Disorders of Thyroid Function Clinical Poster

TRENDS IN PREVALENCE OF THYROID DYSFUNCTION AND ITS ASSOCIATION WITH TOTAL AND CARDIOVASCULAR MORTALITY AMONG US PARTICIPANTS, 1988‐2012

Xiaowen Zhang, Xinlin Zhang*

Affiliated Drum Tower Hospital, Nanjing University School of Medicine, China

Objective: To provide national estimates and temporal trends in prevalence of thyroid dysfunctions over the past three decades in US, and determine the impact of thyroid dysfunction on all‐cause and cause‐specific mortality in US adults.

Methods: We conducted a cross‐sectional analysis of data from 33,140 participants aged 12 years or older with thyroid function data in the National Health and Nutrition Examination Surveys (NHANES) III (1988‐1994), NHANES 1999‐2002, and NHANES 2007‐2012. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2019. The associations between thyroid dysfunctions and mortality were investigated by weighted Cox proportional hazards regression models.

Results: In 2007‐2012, the prevalence of subclinical and overt hypothyroidism, subclinical and overt hyperthyroidism was 4.3% (95% CI, 3.5% to 5.2%), 0.33% (95% CI, 0.23% to 0.48%), 3.2% (95% CI, 2.8% to 3.8%) and 0.2% (95% CI, 0.12% to 0.33%) respectively. In 2007‐2012, 3.7% participants had undiagnosed hypothyroidism (0.16% overt and 3.5% subclinical), and 2.4% had undiagnosed hyperthyroidism (0.07% overt and 2.3% subclinical). The prevalence of subclinical hypothyroidism (4.3% vs. 4.3%) and subclinical hyperthyroidism (3.1% vs. 3.2%) was similar between 1988‐1994 and 2007‐2012, while that of overt hypothyroidism (0.54% vs. 0.33%) and overt hyperthyroidism (0.8% vs. 0.2%) was lower in 2007‐2012 than 1988‐1994. In 2007‐2012, the prevalence of TPOAb and TGAb positive was 11.1% (95% CI, 10.0% to 12.2%) and 15.8% (95% CI, 14.8% to 16.9%) respectively. Older age, White Americans, obesity, TPOAb and TGAb positive were risk factors for hypothyroidism, while older age, women, and Black American were risk factors for hyperthyroidism. TSH levels did not change significantly over time among all populations, while total T4 levels decreased from 1988‐1994 to 2007‐2012. Over a median follow‐up of 17.2 (interquartile range, 10.5 to 26.8) years, all types of thyroid dysfunctions were not associated with risk of all‐cause and cardiovascular mortality, but among individuals aged 65 years or older, subclinical hypothyroidism was associated with a significantly higher risk of total mortality (HR 1.17, 95% CI 1.00‐1.37, p = 0.05) and cardiovascular mortality (HR 1.29, 95% CI 1.04‐1.62, p = 0.02).

Conclusion: The prevalence of subclinical thyroid dysfunction was similar while that of overt thyroid dysfunction decreased in 2007‐2012 than 1988‐1994. Thyroid dysfunctions were not associated with risk of mortality overall, but subclinical hypothyroidism was associated with a higher mortality among individuals aged 65 years or older.

POSTER 316

WITHDRAWN

POSTER 317

History of Thyroid Case Study Poster

DREAMING HIGH: THE JOURNEY OF THREE YOUNG AND VISIONARY PHYSICIANS IN IMPLEMENTING NEONATAL THYROID SCREENING IN BRAZIL

Rui Maciel¹, Luiza Matsumura¹, José Gilberto Vieira¹, Carolina Janovsky*^1,2

¹UNIFESP, Brazil,²USP ‐ CPCE, Brazil

It was 1980 when Brazilian Drs. Luiza Matsumura and Dr. Rui Maciel, both in their early 30s, went to the 8th International Thyroid Congress in Sydney, Australia. At that time, the hottest topic of the meeting was neonatal thyroid screening, that has started to be discussed in Canada, Europe and other developed countries. The main debate laid in which was the best method to perform this test: TSH or T4. However, in Brazil, by that time, this subject was far from being discussed nor thought about. Those young physicians were fascinated by the possibility of avoiding congenital hypothyroidism routinely but the methodology was not currently available at their hometown.

Back to Brazil, the idea of implementing such test was still in their minds but there was no assay to perform it there and it was too difficult to import these assays from abroad. Even the filter paper had to be imported. All those hindrances did not stop those determined researchers from working on a way to gather tools to implement that new and revolutionary screening test in their country.

At this time, they got united to dr. José Gilberto Vieira, another young and innovative endocrinologist, who developed an “in‐house” method to evaluate TSH and T4 in filter paper through radioimmunoassay (RIA). With a grant from Banco do Brasil (FITEC), they have established a new laboratory to perform neonatal thyroid screening in Sao Paulo. The objective of this project was to reduce costs and become independent of imported reagents. That included a special filter paper with the same characteristics, but much lower cost, of the German paper used worldwide.

From 1985 to 1987, more than 20,000 infants have been tested in their laboratory and many publications derived from these results. Drs Matsumura, Maciel and Vieira were also responsible for disseminating the method all over Brazil. Since 1985, thanks to these brave endocrinologists, the neonatal thyroid screening test has turned compulsory in every state of Brazil.

POSTER 318

Iodine Uptake and Metabolism Basic Poster

EFFECTS OF IODINE INTAKE ON GUT MICROBIOTA COMMUNITY AND METABOLITES: INTERACTIONS BETWEEN GUT DYSBIOSIS AND HASHIMOTO THYROIDITIS

Boshen Gong*, Xichang Wang, Yutong Han, Chuyuan Wang, Zhongyan Shan

Institute of Endocrinology, NHC key Laboratory of Diagnosis and Treatment of Thyroid Diseases. The First Affiliated Hospital of China Medical University, China

Objective: Hashimoto thyroiditis (HT) is an organ‐specific autoimmune disease which is associated with iodine intake. It has been increasingly evidence that gut microbiota plays an important role between the gut and the thyroid in HT pathogenesis, which known as the microbiota‐gut‐thyroid axis. However, the mechanism of how iodine intake changes microbiota and causes HT remains exclusive. To investigate the mechanism of iodine intake influences gut dysbiosis and HT.

Methods: We recruited 23 HT patients and 25 healthy individuals in the study to investigate the alterations of gut microbiota composition and metabolic characteristics in HT patients by using 16SrRNA gene sequencing, targeted and untargeted metabolomics. Furthermore, we established a spontaneously develop thyroiditis mouse model with NOD.H‐2h4 mouse by giving 5mg/L, 50mg/L, 500mg/L sodium iodine (NaI) in their drinking water for 10 weeks to explore the underlying mechanisms of different iodine intake influences HT progress. The butyrate group was added sodium butyrate (120mM) in their drinking water during the experiment.

Results: According to the enrichment results, the butanoate metabolism significantly changed in the HT. Clostridium, a potential butyrate producing bacteria was found significantly decreased in the HT patients and the HT mice model, compared with the control group. The relative abundance of Desulfovibrionales was significantly decreased in HT patients, compared with the healthy controls (p < 0.05). Notably, the Desulfovibrionales was enriched in the butyrate mice group. Excessive iodine intake altered the composition and metabolism of gut microbiota, particularly the significantly reduced butyrate acid‐producing bacteria in HT mice. Gut dysbiosis contributes to TH17/Treg imbalanced through the pathway regulated by the reducing butyrate acid. Feeding iodine‐induced HT mice with 120 Mm sodium butyrate (SB) regulated Th17/Treg imbalances through GPR41, and GPR43 and alleviated the lymphocyte infiltration of HT mice in thyroid glands and the level of thyroglobulin antibody (TgAb) in serum by increasing the relative abundance of protective butyrate‐producing bacteria including Firmicutes, Bacilli, and Bifidobacterium.

Conclusions: Excessive iodine intake significantly altered intestinal flora composition, which lead to gut dysbiosis and metabolism changed. Furter, We provided valuable insights for microbiota‐gut‐thyroid axis in HT patients and provided evidence for the national normalization for iodine intake standard.

POSTER 319

Iodine Uptake and Metabolism Clinical Poster

BREAST MILK IODINE CONCENTRATION AND URINARY IODINE CONCENTRATION AS BIOMARKERS FOR THE ASSESSMENT OF IODINE NUTRITIONAL STATUS OF LACTATING WOMEN IN NORTHERN TAIWAN

Jia‐Zhen Li¹, Chang‐Ching Yeh², Chen‐Chang Yang³, Fan‐Fen Wang⁴, Chun‐Jui Huang*⁵

¹Department of Food Safety and Health Risk Assessment Institute, National Yang Ming Chiao Tung University, Taiwan,²Department of Obstetrics & Gynecology, Taipei Veterans General Hospital, Taiwan,³Department of Occupational Medicine and Clinical Toxicology, Taipei Veterans General Hospital, Taiwan,⁴Division of Endocrinology and Metabolism, Department of Internal Medicine, Yangming Branch, Taipei City Hospital, Taiwan,⁵Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taiwan

Objective: Adequate iodine nutritional status in lactating women has been defined by a median urinary iodine concentration (UIC) ≥100 μg/L but breast median iodine concentration (BMIC) can be completely different in women with similar median UIC. Whether BMIC or UIC serves as an accurate biomarker in lactating women in Taiwan, an area with borderline iodine adequacy, is unknown.

Methods: This cross‐sectional hospital‐based study enrolled lactating women who visited Taipei Veterans General Hospital for post‐partum checkups from August 2021 to February 2023. Each participant provided a random spot urine sample for measurement of UIC and two random breast milk samples (one sample from each breast) for determination of BMIC. A blood sample was taken for measurement of thyroid function and a food frequency questionnaire was completed. Iodine measurements were performed using inductively coupled plasma mass spectrometry.

Results: The median UIC of the studied 75 women (mean age: 34.0 ± 4.1 years old) was 87.7 μg/L (IQR: 42.6 ‐ 125.9 μg/L), suggesting insufficient iodine status. However, the overall median BMIC was 168.4 μg/L, indicating the amount of iodine delivered to the infants is sufficient (recommended median BMIC ≥100 μg/L). The positive predictive value for detecting iodine insufficiency by UIC level was 22.0% because 42.7% (n = 32) of the studied women would be misclassified. There was a positive correlation between UIC and BMIC (Pearson correlation coefficient: 0.608); the correlation between thyroid function and UIC or BMIC was weak. Dairy products were the most commonly consumed iodine‐containing food. Women either took multivitamin frequently every day or never took multivitamin (everyday: 29.3%, never: 52.0%). Women not taking multivitamin had a higher likelihood of having BMIC <100 μg/L (adjusted OR: 13.65, 95% CI:1.48 ‐125.92, p = 0.02).

Conclusions: The result of the current study suggests that BMIC is an important biomarker to determine iodine nutritional status in lactating women. Multivitamin intake is an independent predictor for low BMIC.

POSTER 320

Pediatrics Clinical Poster

Maximizing Specimen Adequacy and Reducing Indeterminate Diagnoses in Pediatric Thyroid Nodule Fine Needle Aspiration Biopsy

Matthew Plunk^1,2, David Moe^1,2, Nghia Vo^1,2, Samuel Engle^1,2, Pallavi Iyer^1,2, Kerri Becktell^1,2, Robert Chun^1,2, Cecille Sulman^1,2, Amanda Hopp^1,2, Lauren Parsons*^1,2

¹Children's Wisconsin, USA,²Medical College of Wisconsin, USA

Objective: Fine needle aspiration biopsy (FNA) and use of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) are increasingly utilized in the evaluation and management of pediatric thyroid nodules. Nondiagnostic rates as high as 15‐26% have been reported in this population, and recent literature estimates that indeterminate diagnoses (BSRTC III + IV) comprise approximately 18% of all pediatric FNA interpretations^1‐3. To avoid repeated procedures and reduce indeterminate interpretations, our institution utilizes pediatric‐trained specialists and rapid on‐site adequacy assessment (ROSE); herein, we report our pediatric thyroid FNA data since implementation of this program.

Methods: Between 07/2016 and 12/2022, 163 FNA were performed on thyroid nodules from 119 patients between the ages of 0‐22 years. All FNAs were performed by board‐certified pediatric interventional radiologists, with ROSE and final interpretation by board‐certified pediatric cytopathologists. Quality data collected included BSRTC classification (I‐VI), ROSE findings, number of FNA passes to specimen adequacy, and final diagnosis based on clinical or surgical follow up.

Results: Specimen adequacy rate was 96.9%. Frequency of indeterminate cytologic diagnosis was 14/163 (8.59%); 42.9% of these cases were ultimately found to harbor malignancy. Malignant FNA (BSRTC VI) diagnoses comprised 17/163 (10.4%) of interpretations. All patients who received BSRTC V or VI interpretation were confirmed to have a malignancy (20/20). Overall malignancy rate in our population was 19.3%.

Discussion: FNA performance by pediatric interventional radiology specialists with pediatric pathologist‐performed ROSE resulted in an extremely high rate of specimen adequacy ‐ nearly 97%. Furthermore, our frequency of indeterminate cytologic diagnoses was significantly less than has been reported. These findings reinforce the value of expertise in pediatric interventional radiology and in pediatric cytopathology in the accurate assessment of pediatric thyroid nodules.

POSTER 321

Pregnancy and Development Case Study Poster

MOLAR PREGNANCY INDUCED HYPERTHYROIDISM: ROLE FOR TELEMEDICINE IMPLEMENTATION

Abdulhameed Alhazmi*^1,2, Ibrahim Ajwah¹, Sameerah Alshehri^1,3,4

¹Department of Medicine, Ministry of the National Guard‐Health Affairs, Saudi Arabia,²Jazan University, Saudi Arabia,³College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia,⁴King Abdullah International Medical Research Center, Saudi Arabia

Introduction: Gestational trophoblastic disease (GTD) may be complicated by hyperthyroidism. In the literature, telemedicine showed safety and efficacy in managing hyperthyroidism. We present a case of trophoblastic hyperthyroidism with a suspicious adrenal nodule with the implementation of synchronous telemedicine management.

Description of the case: A 51‐year‐old female with a history of hypertension presented with vaginal bleeding, abdominal pain, anxiety, and palpitations. On examination, she was tachycardic and hypertensive but afebrile with a distended abdomen. Thyroid examination was unremarkable, with no sign of Graves' orbitopathy. Laboratory studies showed a picture of primary hyperthyroidism and elevated β‐HCG more than 800000 IU/L. Abdomen and pelvis imaging revealed two findings: an endometrial hypervascular mass suggestive of GTD and a left hypervascular adrenal nodule suggestive of pheochromocytoma. Adrenal incidentaloma biochemical work came back negative except for plasma metanephrines results which were pending. We started the patient on methimazole to control the hyperthyroid status and atenolol with prazosin to control the heart rate and blood pressure before the suction and curettage. The patient had an uneventful suction evacuation for a complete molar pregnancy, proven by histology. Because the patient is from outside Riyadh, we offered the choice of TM follow‐up for her hyperthyroid status and prazosin adjustments until the results of the metanephrines are released. The patient measured her vital signs at home and visited an affiliated laboratory weekly for thyroid functions and β‐HCG. We called her twice weekly, reviewed her symptoms, vitals, and laboratory results, and adjusted methimazole and the antihypertensive medications accordingly. After two weeks of follow‐up, she achieved clinical and biochemical euthyroid status, and the pheochromocytoma screening came negative. We discontinued methimazole, atenolol, and prazosin after tapering them down and provided a six months appointment for the adrenal nodule follow‐up.

Discussion: Telemedicine can be a proper method to manage patients with hyperthyroidism and as preoperative care for pheochromocytoma. It reduces the travel burden for the patients and exhibits successful outcomes. Further studies are required to consolidate these findings, and guidelines on patients' selection and protocols of adequate telemedicine care for patients with hyperthyroidism are needed.

POSTER 322

Pregnancy and Development Clinical

DOES TARGETING A TSH ≤2.5 MMOL/L IMPROVE FERTILITY IN EUTHYROID WOMEN?

Ismail Nasri*

liberal doctor, Algeria

Introduction: hypothyroidism is among the most frequent causes of infertility, our objective is to analyze this population in order to evaluate the effectiveness of treatment with levothyroxine. Patients and methods: this is a retrospective interventional study from September 2017 to September 2022. Inclusion criteria: infertility, TSH >2.5 mmol/L Exclusion criteria: infertility for less than 1 year, age ≥45 years, other cause of infertility for the woman, spermogram abnormality. Results: our work brought together 82 patients, 41% of whom presented with primary infertility, with an average age of 33 years. 32% have positive Anti TPO Abs, and 40% have a family history of thyroid disease. 33% of patients have a TSH (2.51‐4.5), 51% TSH (4.51‐10), 16% a TSH >10. Targeting a TSH ≤2.5 mmol/L improves the fertility rate by 56% with an average duration of 7 months under levothyroxine. There were 3 cases of abortion or stillbirth, this improvement in fertility is 48% in patients with TSH (2.51‐4.5), 62% for TSH (4.51‐10), 62% for TSH >10.56% in patients with positive Anti TPO Ac, and 67% in patients with negative Anti TPO Ac. Conclusion: our work shows that the use of levothyroxine in patients who consult for infertility with a TSH >2.5 mmol/l clearly improves fertility independently of the level of TSH and Anti‐TPO Ac.

POSTER 323

Surgery Translational Poster

AUTO‐TRANSPLANTATION OF RAT THYROID INTO A PRE‐VASCULARIZED RETRIEVABLE CELL POUCH™ DEVICE FOR THE TREATMENT OF POST‐OPERATIVE HYPOTHYROIDISM

Arash Memarnejadian*¹, Pardis Pakshir¹, Ben Muirhead², Jonathan Mofford², Frank Shannon¹, Philip Toleikis¹

¹Sernova Corp, Canada,²McMaster University, Canada

Objective: Thyroid auto‐transplantation (TATx) to circumvent the need for life‐long exogenous thyroid hormone replacement after total thyroidectomy would significantly advance the field. This study investigated the functional capacity of the Sernova Cell Pouch™ (CP), a retrievable subcutaneous vascularized device, as a potential site for TATx in a thyroidectomized rat model.

Methods: Twenty male Lewis rats were implanted with CP on the ventral surface of the abdominal wall and left for five weeks to allow the formation of a vascularized tissue chamber within the device scaffold. After total thyroidectomy and re‐implanting of parathyroid glands, 19 rats survived, out of which 15 each received a TATx of dissected thyroid lobes into the CP, and 4 rats served as non‐transplant controls. Animals were monitored weekly for weight and blood levels of TSH, FT4 and T3 until week 22 post‐thyroidectomy/TATx. CPs were explanted in survival surgery at week 9 (three rats) and week 20 (ten rats) for histology assessment. Two animals with engrafted devices underwent MicroSPEC/CT imaging for 99m‐Tc pertechnetate radioisotope biodistribution at week 25.

Results: All thyroidectomized animals had an immediate increase in TSH and a decline in T3/FT4 levels. Non‐transplanted controls did not recover hormone levels before euthanasia after four weeks due to humane endpoint weight loss. Their average fold change of hormone level to the baseline was 26 (TSH), 0.05 (FT4) and 0.2 (T3). Transplanted rats restored FT4 and T3 to the baseline level at 4‐ and 7‐weeks post‐TATx, respectively. TSH peaked with a 28‐fold change at week 5, declining gradually to a plateau of 5X baseline from week 11 until week 20 post‐TATx. Upon device explantation, animals returned to overt hypothyroidism. Scintigraphy imaging of two representative animals revealed a total thyroidectomy in one rat and thyroid remnants in the other, with good uptakes at the transplant sites. Immunofluorescence staining of explanted devices showed localized Thyroglobulin and Thyroperoxidase in viable thyroid follicles.

Conclusion: The Cell Pouch‐thyroid transplant strategy demonstrated the potential to restore euthyroidism after total thyroidectomy by preserving the internal control mechanism of thyroid regulation without needing thyroid hormone replacement therapy. This proof‐of‐concept study warrants further evaluation in clinical trials.

POSTER 324

Surgery Clinical Poster

OUTCOMES AND PROGNOSIS OF 34 PATIENTS WITH MINIMALLY INVASIVE FOLLICULAR THYROID CARCINOMA: SINGLE INSTITUTE EXPERIENCE

Dohoon Koo*¹, Phillip Pirgousis²

¹Haeundae‐paik hospital, College of Medicine, Inje University, Korea, Republic of,²Mayo Clinic Florida, USA

(Background) Follicular thyroid carcinoma (FTC) is the second most common thyroid malignant tumor and minimally invasive (MI)‐FTC refers to microscopic focal or limited capsular invasion and/or vascular invasion. Meanwhile, the management of MI‐FTC is still a matter to be debated regarding the appropriate surgical extent and patient‐tailored treatment strategies.

(Objective) we aimed to investigate the clinicopathological characteristics of MI‐FTC patients and to identify related prognostic factors.

(Methods) This is a retrospective cohort study of consecutive patients who underwent surgery due to MI‐FTC at Mayo Hospital Florida. A total of 34 MIFTC patients were identified, and all of them underwent total or completion thyroidectomy, and RAI was additionally performed in about 80%.

(Results) 14 (41.2%) were female and 20 (58.8%) were male, with a mean age at diagnosis of 59 years (range 28–84 years) and a median tumor size of 37 mm (range 6–85 mm). Initial total or near total thyroidectomy was performed in 14 cases (42.4%). In all 19 patients (57.6%) who underwent lobectomy, completion thyroidectomy was performed. When stratified by angio‐invasion, the male ratio was higher (82.1%, p = 0.017), and the median tumor size was statistically significantly larger (5.2cm, p = 0.012) in the angio‐invasion group. In 22 patients who were successfully followed up with the median period of 123 months, the recurrence rate was 18.2% (4/22) and the disease‐related mortality rate was 4.5% (1/22). In addition, the 10‐year disease‐free survival rate was 79%, and although there was no statistical significance, the hazard ratio was higher in the group with size of 40 mm or more [2.88 (0.29, 28.6), p = 0.37] and angio‐invasion [2.42 (0.38, 15.28), p = 0.35].

(Conclusions) Although the number of patients in this study is small, considering the surgical extent performed for MIFTC and the resulting disease‐free survival, MIFTC treatment strategy with poor prognostic factors (>40 mm, vascular invasion) seems to require a more aggressive direction. In the future, a more detailed analysis of the prognosis of MIFTC should be needed through a large‐scale study with an increased number of patients.

POSTER 325

Surgery Clinical Poster

EVALUATION OF SWALLOWING RELATED QUALITY OF LIFE IN PATIENTS UNDERGOING ENDOSCOPIC THYROID SURGERY VERSUS OPEN THYROID SURGERY

Sanjay Yadav*, Parth Deshmukh, Dhananajaya Sharma

NSCB Medical College, India

Introduction: Surgical indication of thyroid surgery in small benign nodules is cosmesis. To improve the cosmesis, transoral endoscopic thyroid surgery (TOETVA) is considered one of the best modalities as it gives no visible scar. However, swallowing related quality of life (SWAL QoL) after TOETVA has not been compared with open thyroid surgery (OTS). The aim of this study is to compare the two modes of surgical therapy on swallowing related quality of life.

Methods: This case control study was conducted prospectively between Sept 2020 and Dec

2022. Patient operated for benign euthyroid nodules undergoing either OTS or TOETVA were included in the study. Swallowing related quality of life was evaluated before and after the surgery and compared for the two groups.

Results: Sixty patients underwent TOETVA and 196 had OTS. Out of 196 OTS patients, 80 age and sex matched cohort was selected as control. Pre‐surgery scores were comparable between the two groups. Postoperatively, short term (1 month) SWAL‐QoL was significantly better in TOETVA group as compared to OTS. However, long‐term (3 months) SWOL‐QoL was comparable in both groups.

Conclusion: TOETVA results in significant improvement in short‐term swallowing related QoL. However, long term SWAL‐QoL is same as open thyroid surgery.

POSTER 326

Surgery Clinical Poster

VOICE CHANGES REPORTED BY OLDER ADULTS AFTER THYROID AND PARATHYROID SURGERY

Jennine Weller*¹, Philip Crepeau¹, Whitney Sutton¹, Zeyad Sahli², Tatiana Fedorova¹, Karen Bandeen‐Roche³, Jeremy Walston¹, Jonathon Russell¹, Lilah Morris‐Wiseman¹, Aarti Mathur¹

¹Johns Hopkins University School of Medicine, USA,²University of Virginia Health System, USA,³Johns Hopkins Bloomberg School of Public Health, USA

Objective: After uncomplicated thyroid and parathyroid surgery, voice changes in the absence of recurrent laryngeal nerve injury occur commonly in younger adults. We aimed to determine the prevalence of pre‐ and postoperative dysphonia in older adults (aged ≥65 years) and evaluate risk factors for these voice changes.

Methods: We queried a longitudinal prospective cohort of 315 older adults (aged ≥65) who underwent thyroidectomy or parathyroidectomy. Fried frailty phenotype was measured at enrollment. Patients completed the Voice Handicap Index (VHI) preoperatively and postoperatively at 1‐,3‐, and 6‐months. Patients with preoperative vocal cord dysfunction, recurrent laryngeal nerve injury, or lack of follow up were excluded. Paired t‐tests compared mean differences in VHI scores. Logistic regression examined risk factors for worsened postoperative dysphonia.

Results: Of 244 older adults, 187 (76.6%) were women, 193 (79.1%) white, and 114 (46.7%) frail/pre‐frail, with a median age of 71 years (range 65‐94). The average preoperative VHI score was 6.6 points (range 0‐56), with 140 (57.4%) patients reporting mild and 13 (5.3%) moderate voice changes at baseline. Postoperatively, 131 (53.7%) patients had a worse voice at 1 month, with a significant increase in mean VHI score by 3 points (p = 0.001). The most commonly reported patient issues postoperatively were difficulty being understood in a noisy room (20.1%) and voice sounds varying throughout the day (21.3%). Female sex (OR 2.15, 95% CI 1.15‐4.01) and minority race (OR 1.93, 95% CI 1.05‐3.55) were associated with worse VHI score at 1 month postoperatively. There was no association between worsened VHI score and age, frailty phenotype, or extent of surgery. By 3 and 6 months postoperatively, there were no significant differences in mean VHI score when compared to preoperative score (p = 0.703 and p = 0.875, respectively). However, at 6 months after surgery, 121 (49.6%) patients still reported worse voice compared to preoperatively.

Discussion/Conclusion: Older adults have a high prevalence of dysphonia at baseline and almost half of patients report worse voice 6 months after surgery despite normal recurrent laryngeal nerve function. These findings should be incorporated in preoperative counseling of older adults undergoing thyroid and parathyroid operations.

POSTER 327

Surgery Clinical Poster

AUTOMATED PARATHYROID GLANDS DETECTION SYSTEM IN SURGICAL VIDEOS DURING ROBOTIC THYROIDECTOMY USING DEEP LEARNING AND EXPLAINABLE ARTIFICIAL INTELLIGENCE

Kyungsu Lee^1,2, Jong‐hyuk Ahn*^3,4, Hyeong Won Yu⁵, Jae Youn Hwang¹, Hyoun‐Joong Kong^2,6, Kyu Eun Lee^7,2,8

¹Daegu Gyeongbuk Institute of Science and Technology, Korea, Republic of,²Seoul National University Hospital, Korea, Republic of,³Chungbuk National University Hospital, Korea, Republic of,⁴lnha University College of Medicine, Korea, Republic of,⁵Seoul National University Bundang Hospital, Korea, Republic of,⁶Seoul National University College of Medicine, Korea, Republic of,⁷Seoul National University College of Medicin, Korea, Republic of,⁸Seoul National University Graduate School, Korea, Republic of

Objective: Preservation of the parathyroid glands during thyroidectomy is important to prevent postoperative hypoparathyroidism. Development of deep‐learning (DL) algorithm to detect parathyroid glands in surgical videos can help preserve parathyroid glands and improve patients' safety. We aimed to develop a DL algorithm to detect parathyroid glands in surgical videos, and to develop an explainable artificial intelligence (XAI) that provides evidence of DL algorithm detection.

Methods: ‘PexNet’ for parathyroid detection was developed and trained. Comparison analysis of performance was performed between ‘PexNet’ and other state‐of‐the‐art algorithms. For internal dataset, 22,584 images were obtained from 47 patients who underwent bilateral axillo‐breast approach robotic thyroidectomy (BABA RT) from 2018 to 2019 using Xi version of robotic system. External validation data (25,364 images) were acquired from the following three groups; 1) BABA RT using previous version of robotic surgical system (Si); 2) transoral robotic thyroidectomy using Xi version system (TORT); and 3) open method (Open).

The primary outcomes; 1) mean Intersection over Union (mIoU); 2) Dice coefficient; and 3) mean Average Precision (mAP).

The secondary outcomes; 1) performance of the XAI model; and 2) decision supporting role (reader test).

Results: mIoU, dice coefficient, and mAP of ‘PexNet’ showed 75.09%, 84.44%, and 0.677, respectively (vs. Yolo v4, 64.11%, 76.27%, and 0.554, respectively). External validation results were as follows; 1) Si, mIoU of 71.3%, Dice coefficient of 81.7%, and mAP of 0.625; and 2) TORT, mIoU of 72.6%, Dice coefficient of 82.7%, and mAP 0,641. The XAI model analyzed the detecting basis of ‘PexNet’ into 4 clusters; 1) color and/or shape of parathyroid (31.7%); 2) light reflection of parathyroid (26.4%); 3) action of robotic instruments (23.4%); and 4) location of robot arms (18.5%). In reader test, ‘PexNet’ improved parathyroid detection by doctors (2.87 improvement in IoU, 4.61% improvement in positive predictive value, and 0.65% reduction in center distance difference).

Discussion/Conclusion: The proposed DL and XAI models showed excellent performance, and can provide decision making for accuracy and safety during BABA RT.

POSTER 328

Surgery Clinical Poster

ENDOSCOPIC THYROIDECTOMY BASED ON ALAR FASCIA ANATOMY, SHOULD THE LYMPH NODE POSTERIOR TO THE RIGHT RECURRENT LARYNGEAL NERVE BE RENAMED AS THE LYMPH NODE POSTERIOR TO THE RIGHT ALAR FASCIA

Bo Wang*, Si‐Ying Lin

Fujian Medical University Union Hospital, China

BACKGROUND: This video demonstrates a method for endoscopic thyroid surgery based on the anatomy of the pterygium fascia.

METHODS: A 32‐year‐old woman with thyroid cancer underwent endoscopic thyroid surgery via a bilateral areola approach. The operation was performed according to the method of fascial anatomy. Using the tension of the alar fascia, a bloodless plane was separated, and the right thyroid lobe, the right central area, and the lymph nodes behind the right recurrent laryngeal nerve were resected. During the intraoperative period, recurrent laryngeal nerve monitoring was used to evaluate the function of the recurrent laryngeal nerve, and the parathyroid gland blood condition was evaluated by ICG angiography.

RESULTS: During the operation, the structure of the alar fascia on the right side of the neck was fully anatomical, and the relationship with the recurrent laryngeal nerve and parathyroid glands was completely displayed. After dissection of the lymph nodes posterior to the right recurrent laryngeal nerve, the prevertebral fascia and cervical pleura were demonstrated.

DISCUSSION: Endoscopic thyroid surgery based on the anatomy of the alar is feasible; it can reduce bleeding during surgery and protect the recurrent laryngeal nerve and parathyroid glands. Given the congenital layer of the alar fascia, it is suggested that the lymph node posterior to the right recurrent laryngeal nerve be renamed the lymph node posterior to the alar fascia.

POSTER 329

Surgery Clinical

SURGICAL MANAGEMENT OF LARGE GOITERS IN THE ENDEMIC ZONES

Demongawi R*¹, Moningo D¹, Pangodi J¹, Mvula ², Kogana F², Longina L², Ngeda G³, Biambi M³

¹University of Kinshasa; ²District Hospital of Gbadolite; ³District Hospital of Gemena, D.R.Congo.

Objective: Large goiters are frequent in the endemic zones and their management is specific. The objective of this study was to report our experience in the surgical management of large goiters.

Methods: This is a prospective study of thyroidectomy including 25 patients in June 2022. the thyroid gland was weighed after surgery. All the patients with goiter were classified according to the WHO Classification. We used Kocher's anterior approach.

Results: The prevalence of large goiter was 53% (25/47). The sex ratio was 0.041 (24 women and 1 man). The mean age of the patients was 40 years with the extremes raging from 25 to 75 years. Thyroid hypertrophy was bilateral in 87%. Most of goiters (80%) were classified stage 4 according to the WHO Classification. Dyspnea was the main symptom of consultation (83%) and 12% were related to esthetical concern. The duration of goiter was on average 15 years with extrems of 5 to 40 years. Patients had euthyroid goiters in 35% and hyperthyroid goiters in 65%. Preoperative preparation for hyperthyroidism was performed in 65% by ATDs. Goiter volume was related to its duration in 89% with a p value = 0.025. Thyroid ultrasound reveled multinodular goiters in 83%. The average weight of the thyroid gland after thyroidectomy was 130 g with the extremes ranging from 60 to 270 g. Total thyroidectomy was performed in 84%; the laryngeal nerve was discovered in 94 of cases. The average operative time was 1 hour 50 minutes. Hemorrhage was the mos perioperative complication in 6%. Postoperative complication was dysphonia (bitonal voice) in 3%.

Conclusion: Large goiters are frequent in the endemic zones of D.R.Congo; the duration of consultation is the favoring factor with mecanical compression. Perioperative preparation by ATDs reduces hemorrhage. Total thyroidectomy by Kocher's anterior approach remains the treatment of choice and offers a satisfactory result when it is well performed.

POSTER 330

Surgery Clinical Poster

CLINICAL APPLICATION OF PECTORALIS NERVE BLOCK II FOR FLAP DISSECTION‐RELATED PAIN CONTROL AFTER ROBOTIC TRANSAXILLARY THYROIDECTOMY: PRELIMINARY RESULTS OF A RANDOMIZED CONTROLLED TRIAL

JA SUNG BAE*, Kwangsoon Kim

Seoul St Mary's Hospital, Korea, Republic of

Objective : Few studies have examined the clinical utility of ultrasonography‐guided pectoralis nerve block II (PECS II) during wide flap dissection of SP robot‐assisted transaxillary thyroidectomy (SP‐RATT). This study presents preliminary results of a randomized controlled trial.

Methods : A total of 48 adult patients (aged ≥20 years) who underwent elective SP‐RATT (including lobectomy) or total thyroidectomy from November 2022 to February 2023 at Seoul St. Mary's Hospital (Seoul, Korea). The patients were divided into a block group (n = 22) and no‐block group (n = 26). Pain was measured using a visual analog scale (VAS) at 4, 24, and discharge day after surgery, and the requirements for rescue painkillers in the post‐anesthesia care unit and ward were recorded. The Korean version of quality of recovery‐15 questionnaire (QoR‐15) was used to assess quality of recovery after surgery.

Results : The demographic variables were comparable between the two groups. The block group had significantly lower VAS scores at 4 h postoperatively (3.0 ± 2.2 vs. 4.5 ± 2.3, p = 0.024). However, no significant group difference was observed after 24 h and at discharge day. The block group had lower VAS scores within 1 day of surgery than the no‐block group, which experienced significant pain relief only after postoperative day 1. The block group required fewer painkillers in the post‐anesthesia care unit than the no‐block group. There was no statistically significant differences between the two groups in all items of the QoR‐15K. However, the block group showed relatively higher scores in the pain item.

Conclusion : PECS II may serve as a new pain relief modality and valuable addition to the current multimodal analgesic strategy for patients undergoing SP‐RATT.

POSTER 331

WITHDRAWN

POSTER 332

Thyroid Cancer Basic Poster

POTENTIATED SUPPRESSION OF CANCER STEM CELL ACTIVITY OF BRAF INHIBITORS BY MEK INHIBITORS IN ANAPLASTIC THYROID CANCER

Takahito Kimura*¹, Woo Kyung Lee¹, Michael Kruhlak², Yuelin Zhu², Li Zhao¹, Karen Wolcott², Sheue‐yann Cheng¹

¹Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, USA,²Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, USA

Background: Anaplastic thyroid cancer (ATC) is very aggressive with limited treatment options. Increasing lines of evidence suggest that cancer stem cell (CSC) activity could underly the recurrence and resistance to treatment in ATC. The recent approval of the combined treatment of BRAF and MEK inhibitors has shown efficacy in patients harboring the BRAFV600E mutation. It is unknown whether these inhibitors could affect CSCs in ATC.

Objective: To evaluate the effects of dabrafenib (BRAF inhibitor), trametinib (MEK inhibitor), and combined treatment on the CSC activity in ATC cells.

Methods: Three human ATC cell lines, 11T, 16T, and 8505C cells, were used in the studies. The effects of these inhibitors, singly or combined, on the expression of CSC markers and CSC activity were analyzed by tumorsphere formation and ALDEFLUOR assays. Additionally, confocal imaging was used to visualize CSC cells expressing a SORE6‐mCherry reporter directly. The effect of inhibitors on xenograft tumor growth was evaluated using flow cytometry (FACS) and immunohistochemistry.

Results: The combined treatment most effectively reduced CSC activity and the expression of CSC markers such as OCT4, cMYC, ALDH1/2, and CD44. Direct visualization of CSC cells by confocal imaging of mCherry‐positive cells revealed that dabrafenib was weak in reducing mCherry‐positive cells in three ATC cell lines (10‐15%). Trametinib reduced mCherry‐positive cells by 50‐60% in these ATC cells. The combined treatment further augmented the reduction to 80 – 90 %. The effect of the inhibitors was further analyzed in vivo xenograft models. FACS analysis of tumors induced by SORE6‐mCherry expressing 8505C cells revealed that treatment with dabrafenib, trametinib, or their combination results in reductions of 33%, 42 %, and 65% mCherry enriched cells. The data indicate that trametinib potentiated the effectiveness of dabrafenib in reducing CSC activity.

Conclusions: Data indicated that trametinib potentiated the effect of dabrafenib in reducing CSC activity. These findings could partially account for the efficacy of the combined treatment shown in ATC patients. That not all CSC activity was totally abolished may account for the recurrence in ATC patients. Our findings have provided new insights into the molecular basis of efficacy and limitations of these drugs in ATC patients.

POSTER 333

Thyroid Cancer Basic Poster

ANK2, THE KEY GENE FOR THYROID CANCER SCREENED OUT BY BIOLOGICAL INFORMATICS

Meng Jia*¹, Qianqian Li¹, Jiawen Liang¹, Ye Qin¹, Xiubo Lu¹, Jianwei Wang²

¹The First Affiliated Hospital of Zhengzhou University, China,²Zhengzhou University, China

Objective: Thyroid cancer is one of the most common endocrine tumors which has a quickly increasing incidence around the world. In the context of the continuing increase in morbidity, the mortality of thyroid cancer is steady or declining due to early diagnoses. But the 5‐year survival rate in advanced patients are only 59%. So it is critical to find new biomarkers and therapeutic targets of thyroid cancer, and that is why we start this study.

Methods: Based on TCGA data, we conducted this study. We used R (version 4.1.3) to analyze the expression level of the ANK family in tumor and paracancerous tissues in human cancers, cBioPortal was used to analyze the gene mutation of ANK family in thyroid cancer. We finished the PPI network through the STRING database (version 11.5; the parameters were default) and it was visualized and beautified by Cytoscape (version 3.7.2).

Results: We found ANK2 showed outstanding results in terns survival and prediction efficiency. The GO and KEGG path way enrichment analysis revealed that ANK2 was significantly enriched in many cancer‐related function. Besides, ANK2 also had an exceptional performance in the survival prognostic prediction. The results above prove that ANK2 is a potential biomarker and a therapeutic target of thyroid cancer.

Conclusion: ANK2 may change the ending of thyroid cancer through affecting the tumor progression, so it is a potential biomarker and a therapeutic target of thyroid cancer.

POSTER 334

Thyroid Cancer Basic Poster

THYROID CANCER PREVALENCE BEFORE AND AFTER THE COVID‐19 PANDEMIC: A CROSS‐SECTIONAL STUDY IN A DOMINICAN REPUBLIC HOSPITAL FROM 2018‐MARCH 15, 2022

Jesus Pichardo*¹, Jose Michel¹, Sebastien Strachan¹, Kelsey Lluberes², Aldo Crespo¹, Sylvia Batista¹, Vicente San Martin¹

¹CEDIMAT, Dominican Republic,²NYU, USA

Background: Thyroid cancer is the most common endocrine cancer in the world and has been attracting attention in recent years due to its increasing incidence. The COVID‐19 pandemic has created a major public health crisis with far‐reaching implications. The data indicates that the number and size of tumors has risen to a large extent in all age groups. The objective of this research paper is to evaluate the prevalence rates of thyroid cancer from 2018 to March 15th, 2022 and to highlight the effect that the COVID‐19 pandemic had on the number of cases of thyroid cancer. Methods: A cross‐sectional study was conducted with data from 2018 to March 15th, 2022 a total of 524 thyroidectomies were performed and data was obtained from a hospital record of one endocrine surgeon. The period denoted as before COVID‐19 pandemic was from January, 2018 to March 15th, 2020 and the after period was from March 16th, 2020 to March 15th, 2022. Results: The results showed a 9.77% increase in thyroid cancer from the before the pandemic period to the after the pandemic period (p < 0.019). The female to male ratio was (4.83:1) which was similar to other studies. The age group with the highest rate of diagnosis was 41‐56 years of age. Our results also suggest that despite the disruptions caused by the pandemic, prognosis predictors such as capsular invasion, vascular invasion, and lymph node metastasis have remained relatively stable before and after the pandemic. Conclusions: This result is consistent with The World Health Organization (WHO) Global Cancer Observatory (GLOBOCAN) database that reported an average annual percentage change of approximately 10.1% in a similar population. It has been argued that this pattern could be attributed to an increase in overdiagnosis by many reasons such as the increase of cancer screening, including ultrasound examination and the usage of highly sensitive imaging modalities. Further research is needed to better understand the underlying causes and to develop effective strategies and guidelines for prevention and control of thyroid cancer while avoiding overtreatment.

POSTER 335

Thyroid Cancer Basic Poster

THE EFFECT OF MIRNA‐SPONGE IN TARGETING MIR‐146B‐5P IN THYROID CANCER

Cesar Fuziwara*, Edna Kimura

Institute of Biomedical Sciences, University of São Paulo, Brazil

The microRNA (miRNA) miR‐146b is a hallmark of thyroid cancer, and its overexpression correlates with BRAF and TERT mutations, and poor prognosis. miRNAs regulate target genes by imperfect pairing to mRNA 3’‐untranslated region, which regulates the protein expression of targets. miR‐146b‐5p shows more than 300 potential targets in TargetScan and the functionally validated targets are involved in cell migration, invasion and in thyroid cell biology. Thus, developing strategies to block miR‐146b‐5p could help understand its function and lead to new translational approaches in cancer. In this context, this study investigates the feasibility of an antisense sponge to block the effects of miR‐146b‐5p in thyroid cancer.

Methods: To construct the sponge plasmids, a fragment that contains SanDI restriction site in XhoI+EcoRI digested pMSCV‐Puro plasmid were prepared and followed by the insertion of antisense sequence to miR‐146b‐5p in the SanDI site to create multiple tandem repetitions. Thus, generated two different sponges containing 6 or 12 repetitions (6X and 12X, respectively). As control, the scramble miR‐146b plasmid was created. The sponge plasmids were transfected into anaplastic thyroid cancer cell line KTC2. For luciferase reporter assays, the plasmids of CBF, NFKB and M50 were used to evaluate the activation of Notch, NFkB and beta‐catenin signaling in a dual‐luciferase assay normalized with Renilla luciferase.

Results: We established the stable cell lines KTC2‐6x and KTC2‐12x that overexpress the 6 and 12 repetitions of miR‐146b‐5p sponge, respectively. To validate the sponge effectiveness, we detected the protein expression of SMAD4, a validated target of miR‐146b‐5p. We observed that both, 6x and 12x sponge increased the levels of SMAD4 in KTC2 cells. Next, we used luciferase reporter assays to evaluate of three oncogenic pathways in thyroid cancer: Notch, NFkB and beta‐catenin signaling. We observed that both miR‐146b‐5p sponges decreased the activation of the luciferase reporters CBF, NFKB and M50 in KTC2 cell lines. In gene expression assays, we evaluated the mRNA levels for thyroid differentiation genes NIS and TPO and we observed a 1.6 and 2.9‐fold increase for NIS, and a 3.1 and 1.7‐fold increase for TPO in KTC2‐6x and 12x, respectively.

Conclusion: this study shows that miR146 sponge is efficient to attenuate the oncogenic pathway and in enhancing the thyroid differentian markers in KTC2 cell line. Therefore, it reveals the potential tool of miR‐sponge to reverse the undifferentiated phenotype of anaplastic thyroid cancer.

POSTER 336

Thyroid Cancer Basic Poster

INTEGRATED ANALYSIS REVEALS A THREE‐GENE SIGNATURE PREDICTION MODEL FOR LYMPHATIC INVASION IN PAPILLARY THYROID CANCER

Ziwei Huang*, Wenjie Xu, Pengfei Yi

Union Hospital, China

Background: Thyroid cancer is one of the most prevalent endocrine cancers with a rising incidence rate over the past decades. Papillary thyroid cancer (PTC) is the dominant historical type. Early lymphatic invasion happens frequently in PTC. However, many of the early lymphatic invasion may be troublesome for detecting due to limited imaging manifestation. Herein, we tried to develop a prediction model for early lymphatic invasion in PTC through transcriptomic analysis.

Methods: RRA afforded us the shared differential expression genes among multiple datasets. GO analysis was performed to identify potential functions. WGCNA was used to analysis the correlations between gene expression patterns and clinical characteristic. Independent prediction factors were verified through the LASSO and Logistic regression. The risk score system was confirmed in two independent cohorts and tissue microarrays. Also, Transwell and wound‐healing assay were verified in PTC cell. GSEA and Immune infiltration analysis revealed the immune factors of lymph node metastasis in PTC.

Results: After quality control, we collected 8 microarray datasets from GEO database and an RNA sequencing dataset from TCGA database. We found the transcriptome profiles were correlated with lymph node metastasis and 3 genes were verified to be independent prediction factors towards statistic approaches. Afterwards, we designed a three‐gene predicable risk score system and effectively confirmed the model in two independent cohorts and tissue microarrays. In vitro assays verified MET and ITPR1 improve migration and invasion while BCL2 attenuated those manners in PTC cell. GSEA and Immune infiltration analysis provided that regulatory T cells might facilitate lymphatic invasion in PTC.

Conclusions: We obtained a predicable model of early lymphatic invasion in PTC patients with moderate accuracy. The three lymphatic invasion related genes were perfectly examined in both bioinformatics methods and in vitro assays.

POSTER 337

Thyroid Cancer Basic Poster

A NEW TYROSINE KINASE INHIBITOR IMPROVES REDIFFERENTIATION‐FACILITATED RADIOACTIVE‐IODINE AVIDITY IN THYROID CANCERS

Ji Min Oh*¹, Prakash Gangadaran^1,2, Ramya Lakshmi Rajendran¹, Chae Moon Hong¹, Byeong‐Cheol Ahn^1,2

¹Kyungpook National University, Korea, Republic of,²BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University School of Medicine, Korea, Republic of

Objectives: Radioactive‐iodine (RAI) therapy is one of mainstay for recurrent and metastatic thyroid cancer patients. However, substantial portion of the cancer exhibits dedifferentiation characteristics along with lack of sodium iodide symporter (NIS) functionality, low expression of thyroid‐specific proteins for iodine‐metabolizing machinery, leading to poor response to the RAI therapy. Therefore, reverting to RAI avidity is crucial strategy to give a new chance of applying RAI therapy to RAI‐refractory cancer. In the current study, we excavated a new tyrosine kinase inhibitor (TKI) and investigated its pharmacological efficiency for enhancing redifferentiation‐faciliated RAI therapy in thyroid cancers.

Methods: The kinase library used in this study was a gift given by the Korea Chemical Bank (http://chembank.org/) of the Korea Research Institute of Chemical Technology. Among the tyrosine kinase inhibitor (TKI) candidates, 3‐cyclohexyl‐1‐[4‐(1,1‐dioxo‐1lambda6,2‐thiazolidin‐2‐yl)phenyl]urea selected as a hit‐compound for subsequent experiments. Four human thyroid cancer cell lines (8505C, HTh7, SW1736 and TPC‐1) with different mutations were exposed to 50 μM TKI for 72 hours. Next, change of biological characteristics, including thyroid‐specific proteins, were assessed. RAI uptake and ¹³¹I‐mediated cell cytotoxicity effects caused by TKI pre‐treatment were also evaluated. In addition, alteration of signaling pathways related to redifferentiation of thyroid cancer by TKI treatment was investigated by western blot analysis.

Results: Application of TKI induced upregulation of thyroid‐specific proteins, including NIS (8505C: 1.26 ± 0.13, HTh7: 2.11 ± 0.69, SW1736: 2.03 ± 0.49, TPC‐1: 1.59 ± 0.48) and restoration of RAI avidity (8505C: 1.71 ± 0.06, HTh7: 1.62 ± 0.33, SW1736: 1.90 ± 0.39, TPC‐1: 2.35 ± 0.79), leading to improved cytotoxicity effect of ¹³¹I in thyroid cancer cells. Moreover, TKI promoted to inhibit phosphorylation AKT and phosphorylation of ERK which are downstream of each PI3K‐AKT and MAPK signaling pathways.

Conclusion: A new TKI have an effect on restoration of thyroid specific proteins expression and RAI‐mediated therapeutic effects via controlling PI3K‐AKT, MAPK pathways. Therefore, it might be applied to convert RAI‐refractory thyroid cancer into a RAI‐sensitive thyroid cancer for enhancing therapeutic effects.

POSTER 338

Thyroid Cancer Basic Poster

ELUCIDATING THE MECHANISMS VIA WHICH THE PROTO‐ONCOGENE PBF STIMULATES CELL MOTILITY IN THYROID TUMOR PROGRESSION

Selvambigai Manivannan*, Merve Kocbiyik, Mohammed Alshahrani, Mohammed El‐Asrag, Ling Zha, Katie Brookes, Hannah Nieto, Martin Read, Andrew Beggs, Chris McCabe, Vicki Smith

University of Birmingham, United Kingdom

Objective: The proto‐oncogene pituitary tumor‐transforming gene binding factor (PBF/PTTG1IP) is overexpressed in multiple tumors, including thyroid cancer, and is associated with tumor progression. In vitro, PBF potently induces cancer cell motility, and both Src‐mediated phosphorylation at tyrosine 174 (Y174) and endocytosis of PBF are required for induction of thyroid and breast cancer cell migration and invasion. This study aimed to further elucidate the mechanisms by which PBF induces cancer cell motility.

Methods: To elucidate molecular events downstream of PBF overexpression, phosphoproteomic and RNA‐Seq analyses of thyroid cells stably overexpressing PBF were performed. We then utilized a novel Pbf knockout (Pbf‐/‐) mouse model with CRISPR/Cas9‐mediated deletion of Pbf exon 4 in C57BL/6N mice. Mouse embryonic fibroblasts (MEFs) were isolated at embryonic day 13.5 and used as primary cultures.

Results: Phosphoproteomic and RNA‐Seq analyses revealed enrichment for molecules involved in cell adhesion and cytoskeleton organization in response to PBF overexpression, prompting further investigation into a physiological role for PBF in cell motility. Pbf‐/‐ MEFs showed a significant reduction in migration and invasion compared with wild‐type (Pbf+/+) MEFs. Interestingly, heterozygote MEFs (Pbf+/‐) showed an intermediate decrease in motility suggesting a gene‐dosage effect. Additionally, the migration of Pbf‐/‐ MEFs transfected with PBF was comparable with Pbf+/+ MEFs in rescue experiments. Initial immunofluorescent studies of Pbf‐/‐ MEFs suggest alterations in focal adhesion (FA) structure and distribution. Importantly, Pbf‐/‐ MEFs demonstrated a marked reduction in focal adhesion kinase (FAK) and paxillin staining with smaller, punctate and more radially distributed FAs compared with Pbf+/+ MEFs.

Conclusions: These findings further confirm a role for PBF in cell motility, through regulating cell adhesion and cytoskeleton organization. Overall, these studies demonstrate a physiological role for PBF in cell motility and further elucidate the mechanisms by which PBF induces cell motility in thyroid tumor progression.

POSTER 339

Thyroid Cancer Basic Poster

PHOSPHORYLATED TERT CONTRIBUTES TO THE PROGRESSION OF PAPILLARY THYROID CARCINOMAS

Kohki Shio*, Yukie Yamaya, Shinichi Suzuki, Yoshiko Matsumoto, Satoshi Suzuki, Fumihiko Furuya

Hikarigaoka, Japan

Objective: Somatic mutations within the promoter of telomerase reverse transcriptase (TERT) occur at high frequency in over 50 distinct cancer types and associated with tumor malignancy and prognosis. These promoter mutations thought to be correlate with higher levels of TERT mRNA, TERT protein, and telomerase enzymatic activity. However, there is little evidence to suggest the association of the status of TERT protein and clinicopathological features of thyroid cancers.

Methods: One hundred twenty participants of papillary thyroid carcinomas (PTCs) were included in this retrospective cohort study. The TERT or Phosphorylated‐TERT (P‐TERT) expression in PTCs were analyzed by immunohistochemistry. Analysis of TERT promoter mutation was using digital PCR system. Based on the prevalence of TERT and P‐TERT expression, we defined a positive patient with staining in more than 15 % of the nucleus in PTC tissues and categorized into 3 groups: TERT+/P‐TERT+, TERT+/P‐TERT‐, and TERT‐/P‐TERT‐.

Results: TERT and P‐TERT protein expression was observed in the nucleus of PTCs. Tumor size of TERT+/P‐TERT+ patient was significantly larger, compared with the that of TERT‐/P‐TERT‐ and TERT+/P‐TERT‐ patients. During the observational period, the recurrence was observed in the 9 of patients. The Kaplan‐Meier curve of TERT+/P‐TERT+ group showed a significant difference and other 2 groups (log‐rank tend, p < 0.001). P‐TERT expression was Univariate analyses showed that the recurrence of PTC was correlated with tumor size, TERT expression, and P‐TERT expression. Multivariate analyses indicated that P‐TERT expression was independent risk factor for the recurrence of PTC.

Discussion/Conclusion

P‐TERT expression is correlated with malignant clinicopathological features of PTC and independent risk factor of the recurrence of PTC. Evaluation of P‐TERT expression might be clinically useful as a prognostic biomarker for PTC patients.

POSTER 340

WITHDRAWN

POSTER 341

Thyroid Cancer Translational Poster

GENOME‐WIDE TRANSCRIPTOME ANALYSIS REVEALS KEY GENES AND PATHWAYS ASSOCIATED WITH THYROID CANCER METASTASIS

Minjing Zou, Amal Qattan, Naif Binjumah, Monther Al‐Alwan, Hazem Ghebeh, Latifa Al‐Haj, Abdulmohsen Altaweel, Khalid Abu Khabar, Falah Almohanna, Abdullah Assiri, Abdelilah Aboussekhra, Ali Alzahrani, Yufei Shi*

King Faisal Specialist Hospital and Research Centre, Saudi Arabia

Metastasis is the major cause of thyroid cancer mortality. However, the mechanisms are still poorly understood. The present study intends to identify genes and pathways in thyroid cancer metastasis. Four murine thyroid cancer cell lines derived from genetically engineered thyroid cancer models were used to generate pulmonary metastasis in nude mice: papillary thyroid cancer (PTC) with BrafV600E mutation (BVE), anaplastic thyroid cancer (ATC) with both BrafV600E and Trp53null mutations (BVE^Trp53null), follicular thyroid cancer (FTC) with KrasG12D mutation (KGD), and poorly differentiated thyroid cancer (PDTC) with both KrasG12D and Cdkn2a‐null mutations (KGD^Cdkn2anull). The metastatic cell lines were established from pulmonary metastatic tumors: BVE‐Met, BVE^Trp53null‐Met, KGD‐Met, and KGD^Cdkn2anull‐Met. Transcriptome analysis showed 88 up‐regulated and 22 down‐regulated genes (log2 fold‐change >2) that were present in all of the Met cell lines. These genes may be considered as hub genes in thyroid cancer metastasis. Gene ontology and pathway analysis identified significantly enriched ontology clusters involved in tumor microenvironment (TME), inflammatory and immune response, and cytokine‐ or receptor‐mediated pathways. Notably, CD274 (PD‐L1) expression was elevated in all Met cells, which likely played an important role in evading host immune surveillance. Mertk, a member of the TAM (Tyro, Axl, Mertk) family of RTKs, was also over‐expressed. MERTK is known to activate multiple signaling pathways (JAK/STAT, MAPK, PI3K/AKT, and PD1/PDL1) in cancer cells to promote tumor cell migration and invasion. Tbxas, a thromboxane A synthase 1 gene which catalyzes the conversion of prostglandin H2 to thromboxane A2 (TXA2), was over‐expressed as well. TXA2 is a potent inducer of platelet aggregation and has been shown to promote metastasis by generating a permissive intravascular metastatic niche. Furthermore, Met cells secreted more pro‐inflammatory cytokines such as CCL2, CCL11, IL5, IL6, and CXCL5, which are known pro‐metastatic mediators in TME. Interestingly, increased expression of CD44 and decreased expression of CD24 were demonstrated in Met cells, which is a characteristic feature of cancer stem cells and epithelial‐mesenchymal transition. BVE‐Met cells developed resistance to BRAFV600E inhibitor PLX4720, but remained sensitive to β‐catenin/KDM4A inhibitor PKF118‐310. In summary, we have identified several targetable genes/pathways in thyroid cancer metastasis. Given the complexity of metastatic cells in evasion of host immune response, simultaneously targeting more than one of these pathways (PDL1, Mertk, IL6, COX‐1/Tbxas1‐TXA2) may be warranted to achieve better therapeutic effect.

POSTER 342

Thyroid Cancer Translational Poster

ENVIRONMENTAL CHEMICALS ASSOCIATED WITH METABOLIC DYSREGULATION IN DIFFERENTIATED THYROID CANCERS

Matthew Smith*^1,2, Xin Hu¹, Yongliang Liang¹, Susan Safley¹, Jennifer Robertson¹, ViLinh Ly¹, Collin Weber¹, Jyotirmay Sharma¹, Neil Saunders¹, Dean Jones¹

¹Emory University, USA,²VA HealthCare System of Atlanta, USA

Background: Incidence of differentiated thyroid cancers, particularly, papillary carcinomas, has increased significantly over the last several decades. The underlying mechanisms responsible for the increased incidence remain unclear. Increased awareness of the association of environmental chemicals in the pathogenesis of human disease has generated new avenues of scientific research. Information regarding the identity of exposures in thyroid cancer remain sparse, and few bio‐surveillance studies have been performed.

Objective: This pilot bio‐surveillance study sought to identify environmental chemicals within three variants of differentiated thyroid carcinomas, and whether any of these chemicals were also associated with metabolic perturbation.

Methods: With IRB approval, we analyzed de‐identified cryopreserved papillary (n = 20), follicular (n = 20), and papillary follicular variant (n = 20) carcinomas from human subjects, which were homogenized and processed for both environmental chemical (GC/MS/MS) and metabolomic (LC/MS/MS) profiling using previously established methods by our team. Five normal thyroid samples, harvested from organ donors served as controls. To identify whether any of these chemicals were associated with metabolic dysregulation, a metabolome‐wide association study of N‐nitrosomorpholine was performed. The R package xmsPANDA was used for bioinformatic and biostatical analysis of both datasets.

Results: Within the carcinoma samples, we identified 257 chemical signatures which were comprised of multiple chemical classes including flame retardants, plasticizers, personal use products, and pesticides. Of those, 50 chemicals were enriched compared to control thyroid tissue. Two of these, the solvent N‐nitrosomorpholine and the fungicide 1,2‐Dibromo‐3‐chloropropane are classified as probable carcinogens. Bisphenol F also was found to be enriched more in the papillary carcinomas compared to follicular or the papillary follicular variant. The metabolome association study revealed 18 metabolic pathways affected including fatty acids, purine, and energy related pathways.

Conclusion: To our knowledge, this is the first study of environmental chemicals in human thyroid carcinoma to date. We identified several chemicals in differentiated thyroid carcinomas which were elevated across all three variants as well as the plasticizer Bisphenol F, which has known endocrine disruption activity, which differed between the cancer types. These results also showed that these chemicals are associated with metabolic dysregulation, suggesting a critical role of persistent organic chemicals in the carcinogenesis of thyroid tumors.

POSTER 343

Thyroid Cancer Translational Poster

CIRCULATING MICRORNAS IN THE FOLLOW‐UP OF PAPILLARY THYROID CARCINOMA PATIENTS

Nathalia Sousa¹, Cesar Fuziwara², Fatima Pasini³, Edna Kimura², Suemi Marui¹, Ana Hoff⁴, Debora Danilovic*^4,1

¹Laboratorio de Endocrinologia Celular e Molecular (LIM 25), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Brazil,²Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Brazil,³Centro de Investigacao Translacional em Oncologia (CTO), Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Brazil,⁴Endocrinology, Instituto do Cancer do Estado de Sao Paulo, Faculdade de Medicina, Universidade de Sao Paulo, Brazil

Objective: Clinical follow‐up of papillary thyroid carcinoma (PTC) patients includes serum thyroglobulin (Tg) dosage and neck ultrasound. Patients treated with lobectomy or without radioiodine (RAI) ablation may have persistent Tg despite no tumor recurrence. Furthermore, the presence of anti‐Tg may interfere in Tg dosage in immunometric assays. In this context, the detection of circulating microRNAs (miRNAs) could be an alternative method in the follow‐up of PTC patients as miRNAs are small stable cell‐type specific RNA molecules differently expressed in tumors compared to normal tissues. The present study aimed to determine differentially expressed circulating miRNAs in patients with metastatic PTC.

Methods: RNA was extracted from plasma samples of 18 PTC patients submitted to total thyroidectomy and RAI therapy: 9 metastatic PTCs (3 exclusive lymph node metastases (LNM), 3 RAI‐responsive distant metastases (DM) and 3 RAI‐refractory DM) and 9 controls (PTCs with excellent response to therapy for >5 years). Circulating miRNAs expression profile was determined by TaqMan^® Low Density Array (TLDA) containing 754 miRNAs and spike‐in control. The miRNAs expression values were used as 2^(‐ΔCt), normalized to miR‐16‐5p. The MultiExperiment Viewer (MeV version 4.5.0) was used for the analysis and to obtain the heatmaps.

Results: Unsupervised hierarchical cluster analysis identified 4 miRNAs differently expressed in metastatic PTCs compared to controls (p < 0.05, FDR <0.05), in which the miR‐17‐5p was significantly overexpressed in metastatic PTCs (fold‐change (FC) +6.86). Similarly, clusters analysis identified dysregulated miRNAs in subgroups comparisons. Three miRNAs were differently expressed in DM compared to controls (p < 0.05, FDR <0.05), among which let‐7c‐5p (FC +6.50) and miR‐484 (FC +2.19) were overexpressed in DM. The cluster analysis revealed three differently expressed miRNAs in DM compared to LNM (p < 0.05, FDR <0.05) and the miRNA‐485‐5p was overexpressed in LNM (FC +3.13). Finally, six miRNAs were overexpressed in LNM compared to controls and the highest dysregulated was miR‐146‐5p (FC +10.24).

Conclusion: Circulating miRNAs are differently expressed in metastatic PTCs and differ according to metastases extension. Apart from circulating miR‐146b‐5p previously associated with PTC recurrence, other miRNAs may not only identify metastatic disease, but also differentiate LNM from DM. Therefore, miRNAs levels represent important circulating biomarkers to diagnose recurrence and predict PTC prognosis.

POSTER 344

Thyroid Cancer Translational Poster

EPS15 HOMOLOGY DOMAIN 1 PROTEIN: A NOVEL BIOMARKER FOR DIFFERENTIATED THYROID CANCER

Anupam Kotwal*, Bhopal Mohapatra, Sukanya Chakraborty, Maddie Fitch, Matthew Storck, Nicholas Whiteman, Joshua Nguyen, Cheng Zheng, Ana Yuil‐Valdes, Benjamin Swanson, Oleg Shats, Robert Bennett, Hamid Band, Whitney Goldner

University of Nebraska Medical Center, USA

Objective: Differentiated thyroid cancer (DTC) generally has a favorable prognosis, however, 30% have progression, highlighting the need to identify additional prognostic biomarkers. Mammalian Eps15 homology domain 1 protein (EHD1) regulates endocytic transport, macrophage proliferation, and T‐cell function (1). EHD1 expression was higher in papillary DTC compared to surrounding tissue in a study of 72 samples (2). Our objective was to identify EHD1 as a biomarker for DTC amongst a larger sample and correlate with clinically meaningful outcomes.

Methods: We performed a retrospective case‐control study of 180 adults with DTC without distant metastatic disease (cases) and 185 adults with benign thyroid disease (controls). Tissue microarray (TMA) of thyroid tissue obtained at surgery was created and analyzed via immunohistochemistry for EHD1 expression. Laboratory investigators were blinded to clinical data to reduce bias. EHD1 staining intensity was categorized as 0 (none), 1 (weak), 2 (moderate) and 3 (strong). EHD1 histoscore was calculated as “staining intensity x % cells stained” and taking an average of 2 cores per sample (or 1 core if the other was insufficient). Mean EHD1 histoscore was compared between cases and controls; a two‐sided p‐value <0.05 was considered statistically significant.

Results: The distribution of histology of cases was 73.5% classic papillary, 17.7% follicular‐variant papillary, 5.5% follicular, and 3.3% oncocytic; lymph node status was 65.2% N0, 19.3% N1a, 15.5% N1b; ATA risk category was 50.3% low, 38.7% intermediate, 11% high‐risk. Cases demonstrated higher EHD1 histoscore compared to benign thyroid tissue (mean 23.8; 95% CI 7.3, 40.3; p = 0.005), even after adjusting for age (linear) and sex (mean 27.7; 95% CI 10.8, 44.5; p = 0.001). The difference was more significant after excluding n = 51 thyroiditis samples from the control group and adjusting for age and sex (41.8; 95% CI 18.0, 65.6; p = 0.0007). EHD1 histoscore was not significantly associated with stage, lymph node status, or ATA risk of cases.

Conclusions: Our pilot study concluded that thyroidal EHD1 expression is a biomarker for DTC in adults. EHD1 expression was not associated with DTC aggressiveness in cases without metastatic disease – this needs further investigation in metastatic DTC to identify a prognostic role of EHD1.

POSTER 345

Thyroid Cancer Translational Poster

KEAP1 DRIVES PEDIATRIC THYROID TUMORS

Nicholas Bambach*, Julio Ricarte‐Filho, Aime Franco

Children's Hospital of Philadelphia, USA

The KEAP1‐NRF2 system is the major regulatory pathway of cytoprotective gene expression in response to oxidative and xenobiotic stress. In unstressed conditions, NRF2 is constitutively suppressed through ubiquitination via the KEAP1‐CUL3 complex and subsequent degradation by the proteasome. Under oxidative stress, NRF2 escapes the inhibitory complex, accumulates in the nucleus, and promotes transcription of cytoprotective genes. The KEAP1‐NRF2 pathway has been found to act as a tumor suppressor and is commonly mutated in many cancers. Here, we aim to search for KEAP1 mutations and identify their effect in thyroid cancer. Mutational analysis was performed using the CHOP Comprehensive Solid Tumor Panel, which tests for 243 cancer associated mutations. HTG EdgeSeq Oncology Biomarker Panel was used to evaluate mRNA expression of samples in our cohort. Mutational analysis and mRNA expression data from TCGA was also analyzed. KEAP1 mutations were found in seven pediatric thyroid tumors from our cohort and two adult thyroid tumors from the Thyroid Cancer TCGA data. In the tumors from our cohort and TCGA, we found significant upregulation of cytoprotective genes including AKR1C3, NQO1, GCLC, and TXNRD1. We validated these targets through knockout experiments. CRISPR/Cas9 was used to knockout KEAP1, and mRNA expression was analyzed via RT‐qPCR. Loss of KEAP1 led to significant upregulation of NQO1, AKR1C3, TXNRD1, GCLC, and EGF. Mutations of KEAP1 dysregulate the degradation of NRF2 and result in its constitutive activation. This accumulation of NRF2 confers increased cryoprotection through activation of NRF2 target genes. The increased resistance to stress is advantageous for cancer cell proliferation and chemoresistance, indicating the importance of this mutation in thyroid cancer. We are currently employing CRISPR/Cas9 to create KEAP1 knockout thyroid cancer cell lines to better understand this tumor suppressor gene on thyroid cancer.

POSTER 346

Thyroid Cancer Case Study Poster

ANAPLASTIC THYROID CANCER IN A FIREFIGHTER: A CASE REPORT AND DISCUSSION OF OCCUPATIONAL RISK

Samantha Diamond‐Rossi*, Ingrid Schneider, Enoch Sanders Jr, Sara Mustafa, Rita Stanislawski, Amin Benyounes

Inova Schar Cancer Institute, USA

Background: Anaplastic thyroid cancer (ATC) is a rare and aggressive undifferentiated carcinoma of the thyroid that is almost uniformly fatal. About 20% of patients have coexisting or a history of differentiated thyroid cancer (DTC) at the time of diagnosis. Firefighters have a higher incidence of thyroid cancer compared to the general population. Here we describe a case of a firefighter who presented with papillary thyroid cancer (PTC) with subsequent transformation to ATC.

Case Presentation: A 64‐year‐old male firefighter was found to have a calcified neck mass on x‐ray. Ultrasound revealed a 4.7 cm right thyroid mass and FNA was consistent with PTC. Lymph node mapping did not reveal suspicious lymphadenopathy and he underwent a total thyroidectomy. Intraoperatively, his thyroid was noted to be adherent to surrounding structures and his post‐operative course was complicated by prolonged intubation secondary to edema. Pathology revealed a 4 cm PTC with extrathyroidal extension and angioinvasion. Two perithyroidal lymph nodes were positive for metastases. While preparing for adjuvant radioactive iodine therapy, he developed a rapidly growing 6 cm thyroid bed mass. CTs of the neck and chest revealed an infiltrative mass extending into the mediastinum with suspected tracheal and esophageal invasion. Due to worsening respiratory symptoms and dysphagia, the patient received a tracheostomy and PEG tube. Repeat FNA showed poorly differentiated thyroid cancer (PDTC) with foci of anaplastic transformation. Molecular testing revealed a BRAF V600E mutation and he was started on combination dabrafenib and trametinib therapy.

Discussion: Firefighters have a higher incidence of thyroid cancer, commonly PTC, than the general population. Toxicity exists from exposure to both protective gear and combustion products such as dioxins and polychlorinated biphenyls. The occupational exposure associated with firefighting is now considered a Group 1 carcinogen by the International Agency for Research on Cancer. While this indicates sufficient evidence of carcinogenicity in humans, there is still inadequate evidence to link firefighting directly to thyroid cancer. One explanation for the increased incidence of thyroid cancer amongst firefighters is surveillance bias due to screening programs aimed at early detection of cancer. Our patient was incidentally found to have a large thyroid mass on x‐ray. His course is significant for rapid de‐differentiation as evidenced by his initial diagnosis of PTC and subsequent transformation to PDTC with foci of ATC. More research is needed to explain the higher incidence of thyroid cancer amongst firefighters and whether their disease course differs from non‐firefighters.

POSTER 347

Thyroid Cancer Case Study Poster

WHAT A PAIN IN THE NECK! ‐ AN UNFORTUNATE CASE OF ANAPLASTIC THYROID CARCINOMA

Nikita Mohan*¹, Ahmed Ahmed², Sami Tahhan¹

¹Eastern Virginia Medical School, USA,²Endocrinology Consultants, Bayview Physicians Group, USA

Introduction: Anaplastic Thyroid Carcinoma (ATC) is a rare type of undifferentiated cancer seen in one to two people per million persons. It is usually seen in women who are 65 or older. Risk factors in developing ATC include prior differentiated thyroid carcinomas, multinodular goiter, and radiation exposure to the neck or chest. We report a case of an elderly female with poorly differentiated ATC.

Description of the Case: A 69‐year‐old female with a past medical history of hypertension, hypothyroidism, hyperlipidemia, and stroke presented from a nursing home with a sore throat, right side neck swelling, neck pain, hoarseness, and shortness of breath for one week, associated with dysphagia to solid foods and odynophagia. Vitals were stable and the physical exam was positive for a large, painless, fixed hard swelling with positive Pemberton sign. Labs showed normal thyroid function. CT Neck demonstrated a 6x4 cm heterogenous right thyroid gland enlargement concerning for a neoplasm with enlarged necrotic right cervical and right submental lymph nodes, along with a 6mm right upper lobe nodule concerning for metastasis. She underwent a flexible fiber‐optic laryngoscopy which demonstrated pooling of secretions and hypomobility of the right true vocal cord. Fine needle aspiration biopsy revealed polymorphic neoplastic cells embedded in a dirty necrotic background with multinucleated giant cells highly suggestive of poorly differentiated ATC.

The patient was started on radiotherapy, levothyroxine, and symptomatic treatment. Despite receiving several cycles of radiotherapy and steroids, her symptoms continued to worsen over a span of two weeks. Due to progressive airway compromise and a lack of clinical response, the patient declined further interventions and pursued comfort care.

Discussion: ATC is an aggressive malignancy with a grave prognosis that tends to metastasize early, with local invasion to the cervical lymph nodes, surrounding structures, and distally to the lungs. In a few patients whose tumors are small and who are treated very aggressively, prognosis is improved. However, ATC has almost a 100% mortality rate with a median survival rate of 5 months when diagnosed at a later stage. Rapid diagnosis is paramount to allow patients to transition to comfort measures soon after diagnosis.

POSTER 348

Disorders of Thyroid Function Case Study Poster

RIDING THE STORM‐ A CASE OF THYROTOXICOSIS ENCEPHALOPATHY SECONDARY TO SOLITARY TOXIC ADENOMA

Nikita Mohan*, Manasi Shah

Eastern Virginia Medical School, USA

Introduction: Thyroid storm is an uncommon, life‐threatening condition with a high mortality rate. Risk factors include untreated Graves' disease, toxic multinodular goiter, or solitary toxic adenoma. However, a patient with subclinical hyperthyroidism secondary to a solitary toxic adenoma causing a thyroid storm is rare. We discuss a patient with a history of subclinical hyperthyroidism presenting with thyrotoxicosis encephalopathy.

Case Study: In January 2023, a 76 yo female presented to the emergency room with a 30lb weight loss over 1.5 months, breathing difficulty, slurred speech, confusion, and weakness for three days. Her past medical history included CKD stage 4, hypertension, MGUS, and subclinical hyperthyroidism. Patient was being followed by an endocrinologist in 2015 for the evaluation of subclinical hyperthyroidism. Imaging and uptake scan demonstrated 19% uptake over 24 hours and imaging showed a hyperfunctioning solitary adenoma of mid left gland with incomplete suppression of the remaining gland. Patient had TSH of 0.04 mcU/mL, T4 1.2 ng/mL, with normal Anti‐TPO and thyroglobulin Ab; therefore, no treatment was initiated. Patient was lost to follow‐up since 2017.

On admission, her physical exam revealed slurred speech and tachycardia. Pertinent labs were: TSH <0.001 mcU/mL, T4 > 7.7 ng/mL, T3 16.3 pg/mL, TSI negative, Hb 8.6 mg/dL, and Na 154 mmol/L. Imaging was unremarkable for any acute process. Burch‐Wartosky score of 35‐45 was indicative of impending thyroid storm. She progressively became encephalopathic with severe agitation, restlessness, and airway compromise. Endocrine was consulted and she was started on hydrocortisone, propylthiouracil, beta‐blockers, and Lugol's solution leading to significant improvement. Sputum cultures returned positive for MSSA, which was likely the triggering event. Cholestyramine was added and PTU was switched to methimazole at discharge.

Discussion: The incidence of thyroid storm ranges from 0.56 to 0.76/100,000 persons per year and is lower when associated with subclinical hyperthyroidism secondary to a solitary toxic adenoma. Our patient's differential diagnosis included stroke, meningitis, metabolic encephalopathy, and delirium. However, all evidence pointed towards solitary toxic adenoma as causative. This case highlights the necessity of close follow‐up of subclinical hyperthyroidism and early management with thionamides, radioactive iodine or surgery.

POSTER 349

Thyroid Cancer Case Study Poster

A CASE OF METASTATIC FOLLICULAR THYROID CARCINOMA ARISING FROM STRUMA OVARII

Aisha Saand*, Samarth Virmani, Elizabeth Jacobi, Richard Robbins, Trisha Cubb

Houston Methodist Hospital, USA

Introduction: Struma ovarii (SO) is a monodermal ovarian teratoma composed of >50% thyroid tissue. Rarely, thyroid carcinoma can arise in SO but metastases are uncommon. We present a case of metastatic malignant struma ovarii (MSO).

Case Description: A 30yo female presented with 2 months of bloating. CT revealed a cystic solid right ovarian mass with ascites. She underwent right oophorectomy and omentectomy. Pathology revealed a 13cm ovarian SO with follicular thyroid carcinoma (FTC) and multiple metastases in the omentum (FIGO Stage IIIB, pT3b NX cMO). In preparation for radioactive iodine (RAI), she underwent thyroidectomy with benign pathology. Following thyroid hormone withdrawal (TSH = 100 mIU/ml; thyroglobulin [Tg] = 19.2 ng/ml; TgAb = negative), she received 100 mCi of I‐131. The post‐treatment whole body scan (WBS) showed uptake in the thyroid bed and throughout the abdomen consistent with peritoneal metastases. One month later, on thyroxine, the Tg was 5.9 ng/ml. She was followed with an unsuppressed TSH and intermittent diagnostic I‐131 WBS that did not demonstrate uptake. However, Tg trended up to 18.6ng/mL. She was lost to follow up for ≈18 months and during this time had an uncomplicated full‐term pregnancy. We first met her ≈4 years since initial diagnosis (6 months post‐partum) with complaints of increasing pelvic pain. Imaging revealed a cystic solid pelvic mass. She underwent surgical resection and pathology showed metastatic FTC involving a 13cm left cystic ovary, omentum, and peritoneum. Molecular testing (50 gene NGS) did not show genetic alterations. Post operatively her non suppressed Tg was 15.4ng/mL. CT showed minimal peritoneal thickening without discrete mass and no evidence of metastatic disease outside the abdomen. I‐131 WBS showed diffuse peritoneal uptake. PET did not demonstrate FDG‐avid disease. TSH is being suppressed with plans for further RAI administration.

Discussion: This case demonstrates a rare presentation of MSO and emphasizes the importance of ongoing surveillance to enable early detection of recurrence. Due to the rarity of this condition, there are no established guidelines on MSO management, highlighting the importance of documenting these cases to better understand and treat this rare condition.

POSTER 350

Thyroid Cancer Case Study Poster

VANISHING PAPILLARY THYROID CARCINOMA IN A PATIENT WITH LYMPHOCYTIC THYROIDITIS AFTER FINE NEEDLE ASPIRATION: A CASE REPORT

Mahreen Hussain*, Justin Koceja, Orly Coblens, Ranjana Nawgiri, Suimin Qiu, Cecilia Clement

University Of Texas Medical Branch, USA

Introduction: Fine‐needle aspiration (FNA) is the most accurate and cost‐effective method for diagnosing papillary thyroid carcinoma (PTC). The Bethesda system reports a positive predictive value of FNA for malignancy of 86.4%. Therefore, in patients with cytology diagnosis PTC, a negative histological diagnosis is rare. We present the case of a patient with PTC and lymphocytic thyroiditis (LT) on FNA with no evidence of malignancy on histology.

Description of the Case

A 69‐year‐old female with hypothyroidism presents with 3 thyroid nodules identified by ultrasound: right lobe (1.9 cm), isthmus (1.7 cm), and left lobe (1.0 cm). Ultrasound‐guided FNA was performed on all 3. Nodule from isthmus showed sheets of follicular cells with enlarged nuclei, pale chromatin, nuclear grooves, and intranuclear pseudoinclusions, classic findings of PTC. The right lobe nodule showed follicular cells in a background of numerous lymphoid cells, consistent with LT. The left lobe nodule showed few follicular cells with cytologic atypia. Two months after FNA patient underwent total thyroidectomy without lymph node dissection. Gross examination revealed a small, atrophic gland with a homogenous pale‐tan tissue and scant red‐brown thyroid limited to the left lobe. Microscopic examination showed the entire thyroid engulfed by an extensive chronic inflammatory infiltrate with lymphoid follicles formation. Close examination of the isthmus biopsy site revealed fibrosis with distorted follicles; some mild nuclear atypia was also noted. However, after thorough review by several pathologists, no PTC was identified. BRAF immunostaining and molecular studies (KRAS, BRAF, NRAS mutations) performed on the isthmus were negative. The original cytological material was reviewed by three cytopathologists and the cytologic diagnosis of PTC remained unchanged. The histological report was signed out as LT, no malignancy identified.

Discussion: We have reported the case of a patient with positive cytology findings and negative histologic diagnosis of PTC. These rare “vanishing tumors” have been described associated with histologic alterations (e.g., fibrosis, hemorrhage, infarction) after FNA due to needle passage. We believe our case is an example of “resolution” of PTC lead by FNA‐induced fibrosis. Pathologists, clinicians, and surgeons should be aware of this unusual but challenging event.

POSTER 351

Thyroid Cancer Case Study Poster

MAMMARY ANALOG SECRETORY CARCINOMA: A CASE REPORT OF A RARE THYROID CANCER

Marnie Aguasvivas Bello*¹, Timothy Kearny², Lyn Jones¹, Paul Fowler¹, Mahsa Mohebtash¹, Deepty Bhansali¹, Jean Park¹, Rebekah Campbell¹

¹MedStar Medical Group, USA,²MedStar Medical Group, USA

Introduction: Mammary analog secretory carcinoma (MASC) of the thyroid is a rare disease that was first discovered in salivary glands and breast tissue. MASC results from an ETV6 gene fusion with NTRK3. MASC in salivary glands is usually indolent, but thyroid‐derived MASC is thought to be more aggressive. It is usually more advanced on presentation compared with papillary thyroid cancer (PTC), presenting with a higher T stage. Local recurrence of thyroid MASC has been described in several cases. This recurrence may be attributable in part to misdiagnosis of the original tumor as PTC followed by inappropriate treatment.

Description of the Case: A 66‐year‐old female presented with a left superior 4.2 cm nodule which was Bethesda Category V on fine needle aspirate. A preoperative laryngoscopy demonstrated left vocal cord paralysis. During total thyroidectomy, the left thyroid mass was found to involve the recurrent laryngeal nerve, the sternothyroid muscle, the muscularis of the anterior esophagus, and a segment of the internal jugular vein. En bloc resection was pursued.

Final pathology revealed a 6 cm MASC of the thyroid with extrathyroidal extension and lymphatic, vascular, and perineural invasion. The diagnosis of MASC was confirmed with gene fusion of ETV6‐NTRK3. The patient underwent positron‐emission test (PET), which showed a left level 3 lymph node that was hypermetabolic. After discussion of the case in tumor board, larotrectinib and external beam radiation therapy were initiated. PET scan after treatment showed that the level 3 lymph node was no longer FDG‐avid.

Discussion: Twelve cases of MASC of the thyroid have been reported previously. Most of these cases were diagnosed after being identified by pathology during repeat operations following original misdiagnosis and treatment for PTC. MASC of the thyroid appears to be more locally advanced than PTC and does not respond to radioactive iodine. Successful treatments involve immunotherapy and radiation. It is critical to be aware of this pathology, and to identify it expediently so as to avoid inappropriate treatment in these patients.

POSTER 352

Thyroid Cancer Case Study Poster

A RARE CASE OF MULTIFOCAL CRIBRIFORM‐MORULAR THYROID CARCINOMA

William Kuenstner*¹, Leila Shobab²

¹MedStar Georgetown University Hospital, USA,²MedStar Washington Hospital Center, USA

Introduction: Cribriform‐morular thyroid carcinoma (CMTC) was considered a rare variant of papillary thyroid carcinoma (PTC), but is now defined as a separate entity in the 2022 WHO classification of thyroid tumors. CMTC has an association with familial adenomatous polyposis (FAP). It shares characteristic nuclear features of PTC but with a cribriform and morular pattern of carcinoma cells. CMTC has a favorable clinical prognosis.

Case Description: 15 year‐old female with no past medical history presented with goiter and dysphagia. She was clinically and biochemically euthyroid. Ultrasound revealed a 6.2 cm left upper to lower pole solid heterogeneous nodule, three additional smaller left sided nodules, and no cervical lymphadenopathy. Ultrasound‐guided FNAB was consistent with papillary thyroid carcinoma. The patient underwent a total thyroidectomy with removal of a large white, firm mass replacing the entirety of the left thyroid lobe. Two additional right lobe nodules were discovered. There was no extrathyroidal extension, lymphatic or angioinvasion, and surgical margins were negative for malignancy. No lymph nodes were assessed. Immunohistochemical stains were positive for beta‐catenin, thyroglobulin, ER, PR, with variable staining for TTF‐1 and PAX8. Scattered small morular structures were positive for CK5/6 and CD5. Molecular analysis was negative for mutations in BRAF. Post‐operatively, she was started on levothyroxine 125 mcg daily, with labs revealing a suppressed TSH, serum thyroglobulin 0.1 ng/mL and thyroglobulin antibody <1.0. She subsequently underwent a I‐123 scan, which had residual activity in the left inferior thyroid bed and a right‐sided focus of activity superior to the thyroid cartilage, representing a lymph node or a thyroid bed remnant. Given the residual thyroid bed remnants, she underwent radioactive iodine therapy with 124.5 mCi. Post ablation therapy scan revealed thyroid remnants in the thyroid bed; she is awaiting further management. The patient was referred to genetic counseling for screening for FAP.

Discussion: we report a rare case of CMTC, which has characteristic clinical, microscopic, immunohistochemical, and molecular features. The course is generally favorable, with low rates of metastasis, recurrence, and mortality. CMTC patients need referral for genetic screening for FAP.

POSTER 353

Thyroid Cancer Case Study Poster

TIME IS OF THE ESSENCE: MEDULLARY THYROID CANCER WITH ECTOPIC CUSHING'S SYNDROME: A CASE REPORT

Hamdan AlAwadhi*, Mahra AlMheiri, Rema ElJabour, Adnan Ajmal, Hammad Hussain

Cleveland Clinic Abu Dhabi, UAE

Ectopic Cushing's Syndrome (EAS) is a rare disease defined by excess synthesis of adrenocorticotropic hormone (ACTH) by a non‐pituitary tumor which is considered an endocrine emergency. Medullary thyroid cancer (MTC) is an uncommon source of ectopic ACTH release. The involvement of MTC and EAS accounts for <1% of all EAS tumors(1). We report a case of a young male who presented with cushingoid features and cervical lymphadenopathy proven to be MTC on biopsy, raising high suspicion of ectopic ACTH. He emergently underwent thyroidectomy and lymph node dissection.

A 20‐year‐old male with history of hypertension and hypokalemia presented to our facility with 3‐month history of lethargy, striae, skin atrophy, truncal obesity with dorsal cervical fat pad along with muscle wasting. Examination revealed moon facies, facial plethora, supraclavicular and dorsal cervical fat pads, and reduced power bilaterally in upper and lower extremities he also had right upper cervical lymphadenopathy. Initial labs showed normal electrolytes and kidney function. ACTH was elevated 29.9pmol/L (1.6‐13.6). There was loss of normal diurnal rhythm of the plasma cortisol concentration. 24‐hour urine free cortisol >7173 nmol/d (14‐177). 1 mg dexamethasone suppression test revealed morning cortisol of 810nmol/L. He had significantly elevated calcitonin level 4,906npg/mL (0.0‐8.4). Plasma metanephrine and catecholamine were normal. MRI of the pituitary was normal. MRI of the chest, abdomen and pelvis revealed a 11mm area of hyperintensity in the right lobe of the thyroid gland and enlarged right cervical lymph nodes. DOTATE PET reported right level 2‐4 cervical lymph node uptake and no distant metastasis. Subsequently he had FNA of right cervical lymph node which revealed metastatic medullary thyroid carcinoma with no evidence of lymphoid tissue. Following a multidisciplinary team discussion, the decision was to start the patient on etomidate infusion seven days prior to his planned total thyroidectomy under close observation in the ICU. Postoperative course was uneventful, labs showed a significant drop in calcitonin level to 36.3pg/ml and ACTH 41.7pmol/L. He received stress dose of steroids in OR and was placed on maintenance hydrocortisone therapy following his surgery which resulted a significant improvement in his symptoms.

Time is of the essence in the management of ectopic ACTH syndrome with overt hypercortisolism. Due to the rarity of this disease, and lack of established guidelines, one should maintain high index of suspicion to ensure timely diagnosis and involvement of experienced multidisciplinary team to adapt the best therapeutic approach and prevent complications(1).

POSTER 354

Thyroid Cancer Case Study Poster

POORLY DIFFERENTIATED THYROID CARCINOMA IN A YOUNG FEMALE WITH A SOMATIC DICER1 MUTATION

Samantha Sovich*, Reema Patel, Stephanie Smooke Praw

UCLA Medical Center, USA

Introduction: The DICER1 gene is involved in RNA interference including processing of microRNAs and has a major impact on gene expression. DICER1 Syndrome caused by a germline mutation is a rare autosomal‐dominant disorder that predisposes to a variety of malignant and noncancerous tumors. With regard to thyroid manifestations, it is well‐studied that patients with DICER1 mutations may develop multinodular goiter (13%) and have a 20 fold increased risk of well‐differentiated thyroid cancer. Here we present a case of poorly differentiated thyroid carcinoma (PDTC) with a DICER1 mutation.

Case Description: A 22‐year‐old woman with history of obesity presented with neck enlargement and was found to have a 5.3 cm right thyroid nodule on ultrasound. She was biochemically euthyroid. She had no family history of thyroid cancer or nodules. She underwent fine needle aspiration demonstrating follicular neoplasm and Afirma testing with a DICER1:p.D1709N c5125G>A mutation that was suspicious for malignancy (∼50%). Subsequently, she underwent right thyroidectomy, followed by completion thyroidectomy with one lymph node sampled. Pathology was significant for multifocal disease with a 6.3 cm poorly differentiated thyroid carcinoma on the right. The tumor was encapsulated, with no extrathyroidal extension, no involvement of surgical margins but notable for capsular invasion, extensive angioinvasion (≥ 4 vessels), and one metastatic perithyroidal lymph node (2 mm without extranodal extension). Post‐operative diagnostic PET/CT did not show evidence of metastatic disease. The patient underwent adjuvant RAI therapy (161.3 mCi). Stimulated thyroglobulin was elevated 34.3 ng/ml and whole body scan showed uptake only in the neck and no evidence of distant disease.

Discussion: While patients with DICER1 mutations are typically found to have benign multinodular thyroid disease with a low risk of well‐differentiated thyroid cancer, our patient presented with a DICER 1 mutation, independent of DICER1 Syndrome and PDTC. On review of the available literature, there is a case series describing six pediatric patients with DICER1 mutations and PDTC. The mutation noted on our patient's cytopathology has been associated with PDTC. The case highlights the importance of awareness of the potential for certain DICER1 mutations to be associated with more aggressive thyroid cancers.

POSTER 355

Thyroid Cancer Case Study Poster

PULMONARY METASTATIC FOLLICULAR THYROID CARCINOMA WITHOUT INTRATHYROIDAL PRIMARY THYROID CANCER

Sima Saberi, Nazanene Esfandiari*

University of Michigan, USA

Introduction: Follicular thyroid cancer is the second most common differentiated thyroid cancer. Metastases occur hematogenously with the most common sites being lung and bone. Metastic disease without an intrathyroidal primary cancer is rare. We hereby present a case of a patient presenting with multifocal pulmonary metastatic follicular thyroid cancer with no primary source within the thyroid gland.

A 44‐year‐old woman with a history of hysterectomy with bilateral oophorectomy, and gastric bypass surgery with stomach pouch tightening presents with abdominal pain. Abdominal CT showed no acute intra‐abdominal finding, but incidental bilateral lung base nodules were seen. A follow up chest CT demonstrated 4 left lung nodules and 1 right lung nodule with the largest measuring 15 mm. She underwent biopsy of the largest nodule with pathology read as benign thyroid tissue. Her serum TSH was 1.63 mIU/L (0.3‐5.5), serum thyroglobulin 40.9 ng/ml with no thyroglobulin antibodies. She was referred to a tertiary care center where a follow up chest CT 6 months from her original chest CT showed stable lung nodules. Review of her lung nodule pathology slides demonstrated well‐ differentiated metastatic follicular thyroid carcinoma. Immunohistochemical stains were positive for TTF‐1 and thyroglobulin, negative BRAF. Due to the discrepancy in pathology reports the patient requested a second lung biopsy at the tertiary center. This core biopsy showed thyroid tissue with microfollicular architecture, favoring metastatic follicular carcinoma. Next generation sequencing of this tissue revealed NRAS (Q61K) mutation. Thyroid ultrasound revealed cystic nodules. PET/CT scan only showed FDG‐avid lung lesions. Surgical pathology slides from her hysterectomy with bilateral oophorectomy showed no evidence of malignant struma ovarii. She underwent a total thyroidectomy with pathology showing no evidence of thyroid cancer. Post‐operatively a thyroid hormone withdrawal radioiodine scan showed multifocal bilateral iodine avid pulmonary metastases with thyroglobulin of 179.8 ng/ml (TSH 151.3 mIU/L), and undetectable thyroglobulin antibody. 261 mCi of radioactive iodine was given. Chest CT 2 months later demonstrated a nearly 50% decrease in the lung nodules size and thyroglobulin was 2 ng/ml (TSH <0.01) without thyroid antibodies.

Conclusion: Pulmonary thyroid tissue is uncommon. The presence of this should raise suspicion for thyroid cancer.

POSTER 356

Thyroid Cancer Clinical Poster

EXTENT OF SURGERY FOR UNILATERAL PAPILLARY THYROID CANCER WITH NONSUSPICIOUS CONTRALATERAL NODULES BY ULTRASOUND IS ASSOCIATED WITH RECURRENCE: AN ANALYSIS OF 1293 PATIENTS

siyuan xu*, hui huang, shaoyan liu, jie liu

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China

Objective: The discussion about surgical treatment of patients with papillary thyroid cancer (PTC) has been an ongoing issue, which is mainly focused on the characteristics of tumor, but rarely on nonsuspicious contralateral nodules. We aimed to compared recurrence‐free survival (RFS)/progression‐free survival (PFS) for unilateral PTC patients with nonsuspicious contralateral nodules by ultrasound after different extent of surgery.

Methods: This retrospective cohort study included a review of PTC patients treated from 2015 to 2017. Adult patients with unilateral PTC and nonsuspicious contralateral nodules by ultrasound were enrolled. Primary tumor size >4cm, gross extrathyroidal extension, tumor confined in the isthmus, clinical lymph node metastasis or pathological lateral neck metastasis and distant metastasis were exclusion criteria. The association between extent of surgery and RFS/PFS were analyzed by Kaplan‐Meier method and Cox proportional hazards model. Data analysis was performed from September 1 to 30, 2022.

Results: A total of 1293 PTC patients (mean [SD] age, 47.0 [10.5] years; 1042[80.6%] women; 595[46.0%] total thyroidectomy (TT), 523[40.4%] lobectomy+nodule enucleation, 175[13.5%] lobectomy,) were analyzed. With extend of surgery extended, patients were more likely to be older, more multifocality for tumor and contralateral nodules, have larger contralateral nodules and primary tumors, and more mETE (all P < 0.05). After a median follow‐up of 45 months, significant growth (>3mm) was identified in 24(4.6%) and 19(10.9%) patients in the lobectomy+nodule enucleation group and lobectomy group, 7(1.2%), 14 (2.7%) and 11(6.3%) structural recurrences, and 7 (1.2%), 11 (2.1%) and 7 (4.0%) progression in disease were identified in the TT, lobectomy+nodule enucleation and lobectomy group, respectively. Unadjusted and adjusted RFS/PFS were significantly worse for patients treated with lobectomy than those who underwent lobectomy+nodule enucleation or TT (3 year‐RFS, 95.5%, 98.2% vs. 99.0%; 3 year‐PFS, 97.9%, 98.9% vs. 99.0%) (all P < 0.05), but difference lost statistical significance with regard to PFS between lobectomy+nodule enucleation and TT (unadjusted P = 0.226, adjusted P = 0.150).

Conclusions: Due to the subtle change of nodules and acceptable prognosis, lobectomy is a considerable option for unilateral PTC patients with nonsuspicious nodules, and lobectomy+nodule enucleation may be an effective alternative to optimize quality of life, when expected similar prognosis of TT.

POSTER 357

Thyroid Cancer Clinical Poster

SURGICAL MANAGEMENT OF PAPILLARY THYROID CARCINOMA IN A THYROGLOSSAL DUCT CYST

Robin Hilder*¹, Stephanie Praw²

¹Olive View, USA,²UCLA, USA

Introduction: Thyroglossal duct cysts (TDC) are the most common congenital anomaly in the neck. The standard surgical treatment is the Sistrunk technique which involves excision of the cyst, the thyroglossal duct and the central hyoid bone. 2 Up to 62% of these cysts contain thyroid follicular cells which can predispose to malignancy. 3 Carcinomas within TDCs are reported in less than 1% of all cysts, and 80% of these are papillary thyroid carcinomas (PTC). 4 5 Compared to PTCs originating in the thyroid gland, these PTCs can grow larger, involve distant lymph nodes and present earlier. 2 In this report, we present a case of PTC in a thyroglossal duct who underwent two surgical procedures for definitive management.

Case Description: A 33‐year‐old female presented with a palpable mass in the anterior neck for 6 months. Ultrasound demonstrated a normal thyroid and 1.6cm x 1.9cm x 0.9 lesion superior to the isthmus with calcifications and peripheral vascularity. The mass was resected, and pathology reported as PTC with involved inked margin. The patient was followed up in Endocrinology, she was clinically euthyroid, with no palpable recurrence. MRI neck demonstrated lingual tonsillar tissue, no thyroid lesions and a signal in the midline subcutaneous tissue. The patient was diagnosed with PTC in a TDC. Given involvement of the inked margins and BRAF V600E mutation on pathology, she underwent Sistrunk procedure with completion thyroidectomy. Final pathology reported normal thyroid parenchyma and a TDC, both negative for malignancy. As such, the patient did not undergo radioactive iodine ablative therapy.

Discussion: This patient underwent TDC cyst resection followed by completion Sistrunk and thyroidectomy, which ideally would have been performed as the initial procedure. 6 This case highlights the need for comprehensive pre‐operative evaluation. The extent of thyroid surgery for a patient with TDC PTC is debated but a Sistrunk procedure is considered standard. Despite favorable five‐year survival rates for PTC, the high rate of local metastases to the thyroid makes the addition of a total thyroidectomy an appropriate approach. Pre‐operative evaluation of radiographic features, lymph node metastases, and mutation analysis, help risk stratify the patient for surgical approach. 4,7

POSTER 358

Thyroid Cancer Clinical Poster

A PILOT TRIAL OF CAMRELIZUMAB PLUS APATINIB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC, RADIOACTIVE IODINE‐REFRACTORY DIFFERENTIATED THYROID CANCER

Xin Zhang^1,2, Di Sun^1,2, Zhuan‐Zhuan Mu^1,2, Yu‐Qing Sun^1,2, Cong Shi^1,2, Ying‐Qiang Zhang^1,2, Yan‐Song Lin*^1,2

¹Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & PUMC, China,²Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, China

Objective: Although encouraging efficacy of tyrosine kinase inhibitors (TKI) has been observed in patient with locally advanced or metastatic, radioactive iodine‐refractory differentiated thyroid cancer (RAIR‐DTC), disease progression will finally occur and limited salvage options can be further chosen. This pilot study (NCT04560127) explored camrelizumab (anti‐programmed cell death‐1 antibody) plus apatinib (mainly targeting VEGFR2) in patients with locally advanced or metastatic RAIR‐DTC.

Methods: Patients received camrelizumab 200 mg once every 2 weeks and apatinib 250 mg once daily until disease progression, intolerable toxicity, or withdrawal of consent. Prior use of TKIs (including apatinib) was permitted, while prior use of ICIs was not allowed. Efficacy and safety were preliminarily reported.

Results: Between September 2020 and December 2021, a total of 10 patients were enrolled (median age, 55 years [range, 37‐68]). All patients had lung metastases and 2 (20%) patients had brain metastases at baseline. Six (60%) patients had TKI‐treated disease, and 3 of them had received at least two different TKIs. The objective response rate was 50% (5/10) and the disease control rate was 100%. By the data cutoff date on March 13, 2023, the median follow‐up duration was 18.2 months (95% CI, 4.6‐28.2). Median progression‐free survival was 19.4 months (95% CI, 3.7‐not reached). Median duration of response and time to progression were not reached and 19.4 months (95% CI, 3.7‐not reached), respectively. Median overall survival was not reached. The most common grade ≥3 treatment‐related adverse events were increased alanine aminotransferase (30%), increased gamma‐glutamyltransferase (30%), and increased aspartate aminotransferase (20%). No treatment‐related deaths occurred.

Conclusion: Camrelizumab plus apatinib shows preliminary antitumor activity and acceptable safety profile in patients with RAIR‐DTC, including those with TKI‐treated disease.

POSTER 359

Thyroid Cancer Clinical Poster

AMERICAN THYROID ASSOCIATION RISK STRATIFICATION AND LONG‐TERM OUTCOMES OF DIFFERENTIATED THYROID CANCER: A TWENTY‐YEAR FOLLOW UP OF PATIENTS IN SAUDI ARABIA

Anwar Jammah*¹, Ibrahim AlSadhan¹, Ebtihal Alyusuf², Mubarak Alajmi³, Abdullah Alhamoudi⁴, Mohammed Al‐Sofiani^1,5

¹King Saud University, Saudi Arabia,²Medical Complex, Government Hospitals,, Bahrain,³, Prince Mohammed bin Abdulaziz Hospital, Ministry of Health,, Saudi Arabia,⁴King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia,⁵The Johns Hopkins University, USA

Objective: Studies have reported differing factors associated with poor outcomes in patients with differentiated thyroid cancer (DTC). We aimed to describe our 20 years' experience on the management of DTC and identify predictors of treatment outcomes.

Methods: We conducted a retrospective review of medical records of patients with DTC seen in the Thyroid Center at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia between the years 2000 and 2020. Demographic and clinical data including pathological characteristics were collected. The American Thyroid Association (ATA) risk stratification was determined for all patients at post‐operative period as well as the response to the therapy at the final follow up visit.

Results: A total of 674 patients (mean age: 47.21 years) with DTC, of whom 571 (84.7%) women were included with mean follow up of 74 months. There were 404 (60.0%) patients with ATA low risk, 127 (18.8%) with intermediate risk, and 143 (21.2%) with high risk. Overall, 461 patients (68.4%) had an excellent response to treatment and 65 (9.6%) indeterminate response 83 (12.3%) with biochemical incomplete and 65 (9.6%) with structural incomplete response. Patients who had an excellent response were mostly ATA low risk (n = 318 of 431, 68.1%), whereas 40 of 65 patients (61.5%) of those with ATA high risk had structural incomplete response to treatment. There were significantly more women who had an excellent response compared to men. Obesity, lymphovascular invasion, and size of tumor were significant predictors of worse outcome to therapy.

Conclusion: The tumor size, lymphovascular invasion, and obesity are strong predictors of a worse response to therapy. Patients with obesity should be carefully followed up regardless of their risk stratification. ATA risk stratification is well correlated with patient long‐term outcomes.

POSTER 360

Thyroid Cancer Clinical Poster

SURVIVAL BENEFIT OF POSTOPERATIVE RADIOIODINE THERAPY AMONG PATIENTS WITH INTERMEDIATE‐RISK DIFFERENTIATED THYROID CARCINOMA

Jinwen Wang*¹, Yaqian Mao², Wei Lin¹, Gang Chen¹, Junping Wen¹

¹Department of Endocrinology, Key Laboratory of Endocrinology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, China,²Department of Internal Medicine, Fujian Provincial Hospital South Branch, Shengli Clinical Medical College of Fujian Medical University, China

Abstract

Objective: The 2015 American Thyroid Association (ATA) guidelines proposed the ATA Risk Stratification System and American Joint Committee on Cancer Tumor‐Node‐Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision‐making. However, the management of patients with intermediate‐risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate‐risk DTC after surgery.

Methods: This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2000‐2019). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan‐Meier method and log‐rank test to analyze overall survival (OS) and cancer‐specific survival (CSS).

Results: Kaplan‐Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log‐rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan–Meier curves of CSS in age cutoff of 55 years showed a significant association (log‐rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44–0.80]), however age (≥55) years associated with worse CSS ([HR] 8.91, 95% confidence interval [95% CI 6.19–12.84]).

Conclusions: RAIT improves OS and CSS in patients with intermediate‐risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision‐making. Therefore, we need individualized treatment plans.

POSTER 361

Thyroid Cancer Clinical Poster

RISK FACTORS FOR STRUCTURAL RECURRENCE IN MEDULLARY THYROID CANCER

Shin Jeong Pak, Yu‐mi Lee, Douk Kwon*, Byung‐Chang Kim, Jae Won Cho, Won Woong Kim, Tae‐Yon Sung, Ki‐Wook Chung

Asan medical center, Korea, Republic of

Objective: Medullary thyroid cancer (MTC) has higher rates of recurrence and worse prognosis than differentiated thyroid cancer (DTC). The aim of the study was to identify the risk factors to predict structural recurrence in patients with MTC.

Methods: We retrospectively reviewed patients who underwent thyroidectomy and neck lymph node dissection for MTC at Asan Medical Center between 1995 and 2018 in Korea. The independent risk factors of structural recurrence were evaluated using univariate and multivariate logistic regression analyses.

Results: A total of 126 patients were included in the study, with a median follow‐up period of 9.98 ± 4.89 (range; 1.25 ∼ 24.42) years. 5 patients (4.0%) died from disease‐specific causes during the follow‐up period. Of the 126 patients, 23 (18.3%) experienced structural recurrence. In univariate analysis, multiple factors (tumor size ≥2cm, pN1, metastatic LN ≥10, lymphovascular invasion, preoperative calcitonin level ≥500, postoperative calcitonin level at 3 months after surgery ≥10 [pg/mL] and calcitonin ratio (CR)) are expected to be risk factors for recurrence. Postoperative calcitonin level at 3 months after surgery ≥10 [pg/mL] (HR 15.561, 95% CI 3.219 ∼ 75.224, P = 0.001), CR ≥0.125 (HR 2.973, 95% CI 1.209 ∼ 7.310, P = 0.018) and pN1 (HR 31.385, 95% CI 2.144 ∼ 459.360, P = 0.012) were significant risk factors for structural recurrence in both univariate and multivariate analyses.

Conclusions: Postoperative calcitonin level, calcitonin ratio and pN1 are important predictors of structural recurrence in patients with MTC, which may help determine effective treatment strategies and follow‐up plans for these patients.

POSTER 362

Thyroid Cancer Clinical Poster

SURVIVAL TRENDS OF DIFFERENTIATED THYROID CARCINOMA IN THE PEDIATRIC POPULATION AFTER RADIOACTIVE IODINE TREATMENT

Emily Persons*, Mohammad Hussein, Marcela Herrera, Eman Toraih, Emad Kandil

Tulane University School of Medicine, USA

Objective: Radioactive iodine (RAI) therapy is a widely accepted treatment for differentiated thyroid carcinoma. This study aims to compare the outcomes of radioiodine (RAI) therapy to other surgical interventions without RAI in pediatric patients with differentiated thyroid carcinoma.

Methods: This study investigated survival trends in patients under the age of 22 who were diagnosed with single follicular or papillary thyroid carcinoma. Data from the Surveillance, Epidemiology, and End Results (SEER) registries 17 and 22 were used, and patients with radiotherapy, prior other cancers, or thyroid cancer diagnosed at autopsy were excluded. Statistical methods, such as Cox proportional hazards, univariate, and multivariate logistic regressions, as well as Kaplan‐Meier survival curves, were used to analyze the data.

Results: The study population consisted of 5,318 patients, of which 55.9% underwent RAI and 82.5% were female. Those who received RAI had a mean survival time of 103 months (95% CI, 52.0‐156.0), while those who did not had a mean survival time of 79 months (95% CI, 32.0‐144.0). Furthermore, black and American Indian/Alaskan Native (AI/AN) had a significantly higher risk of mortality (HR of 3.81 and 8.18, respectively, p = 0.038 and p = 0.045) while those who underwent surgery were found to have a significantly reduced risk of mortality compared to those who did not (HR of 0.08, p = 0.019).

Conclusion: RAI has been shown to improve survival times compared to other treatments alone in pediatric patients. However, pediatric oncologists should take into account the higher mortality rate among black and AI/AN patients when making treatment decisions.

POSTER 363

Thyroid Cancer Clinical Poster

SEX DISPARITIES IN THYROID CANCER INCIDENCE ARE DRIVEN BY DIFFERENTIAL ULTRASOUND RATES

Sara Fernandes‐Taylor*¹, Erin Bowles², Manasa Venkatesh¹, Rachael Doud², Craig Krebsbach¹, Natalia Arroyo¹, Bret Hanlon¹, Louise Davies^3,4,5, Oguzhan Alagoz¹, David Francis¹

¹University of Wisconsin‐Madison, USA,²Kaiser Permanente Washington, USA,³The VA Outcomes Group, Department of Veterans Affairs Medical Center, USA,⁴Geisel School of Medicine at Dartmouth, USA,⁵The Dartmouth Institute for Health Policy and Clinical Practice, USA

Objective: Expanding ultrasound (US) use has increased detection of thyroid cancer. Incidence has always been higher among women, a disparity that has grown over time. The sex difference in thyroid cancer is understudied in the context of diagnostic testing, particularly among privately insured adults where thyroid cancer is most common. We performed a novel longitudinal analysis of the association between thyroid US, fine needle aspiration biopsy (FNAB), and cancer incidence by sex in an integrated health system.

Method: This retrospective cohort study of Kaiser Permanente of Washington enrollees evaluated thyroid US, FNAB, and cancer incidence by sex. Data included claims for patients who underwent thyroid US from 1997‐2019 linked to SEER tumor characteristics. Estimated were (1) annual overall US, FNAB, and cancer incidence rates, (2) proportion of US requiring FNAB, and (3) cancer diagnoses per FNAB. A Poisson model with offset determined the relationship between sex and the proportion of US requiring FNAB adjusting for in‐network status and sociodemographic characteristics.

Results: 55,045 patients underwent US (78% women; mean age 56). US rates increased 5‐fold among men (0.001 to 0.005) and >4‐fold among women (0.003 to 0.013) between 1997 and 2019. FNAB rates also increased over time (annual percent change: 2.27 in women vs. 4.89 in men). Overall, FNAB rates per US changed little over time (0.4). FNAB per US were greater in men (0.45 vs 0.39 in women). Cancer incidence was higher in women over the study period, but cancer incidence per FNAB was similar between sexes (both 0.06, p = 0.4). The Poisson model confirmed that men receive more FNAB following US than women (β = 0.06[0.02], p = 0.02).

Discussion: Sex disparities in US rates are stark. Interestingly, US triggering FNAB was more common in men and changed little over time. Cancers diagnosed per FNAB remained stable regardless of sex. Although the overall differences between sexes for FNAB and cancer were large, the differences relative to US use were small. The large established sex difference in thyroid cancer incidence derives primarily from differential US referrals.

POSTER 364

Thyroid Cancer Clinical Poster

CLINICOPATHOLOGICAL PROFILE OF PAPILLARY THYROID CANCER WITH HUMAN PARVOVIRUS B19: A CASE‐CONTROL STUDY AT TERTIARY CARE CENTRE IN INDIA

Gyan Chand*, Ujjwala Ghosal, Anjali Mishra, Prathyusha Godi

Sanjay Gandhi Post Graduate Institute of Medical Sciences, India

Background: The incidence of papillary thyroid cancer has increased dramatically in recent decades [1]. Although this increase has been attributed to improved imaging modalities, the question arises as to whether other environmental factors, such as infectious agents are influential [2,3].

Objective: To Correlate the presence of Human Parvo Virus B19 in Papillary thyroid cancer tumour with clinicopathological profile of Indian Patients.

Methods: After approval from Institute ethical committee, all adult patients who underwent thyroidectomy for the papillary thyroid cancer and for the benign tumours from Jan 2021 to Dec 2022 were included in the study. The 2mg tissue was collected from the papillary thyroid tumour and from the normal thyroid in patients who were operated for the unilateral benign tumours. The DNA of Parvovirus B19 Various was extracted from both the group and correlated with clinical, pathological and biochemical parameters including thyroid function tests.

Results: Total 35 patients with papillary thyroid carcinoma in study group and 36 patients with normal side thyroid tissue were analysed as a control group. The mean age was 38.3 years, M:F ratio was 1:2. The prevalence of parvovirus B19 infection in papillary thyroid carcinoma patients was 62.50% which was significantly higher than the control group (7.30%) (p = 0.001). In the papillary thyroid carcinoma group, a significant positive correlation was found between tumour size (mean size = 38.73cm vs 36.88cm) and TSH (3.35mIU/l vs 3.32mIU/l). The mean weight of tumour was higher in virus negative group (121.08gm vs100.56gm). the mean duration of thyroid swelling was lesser in thyroid cancer then benign group (32.2 months vs 34.6 months).

Conclusion: The prevalence of parvovirus B19 infection was higher in patients with papillary thyroid carcinoma than in the control group. The papillary thyroid carcinoma patients with positive B19 infection have smaller tumour, higher TSH and shorter duration of presentation compared with B19 negative PTCs.

POSTER 365

Thyroid Cancer Clinical Poster

CHEK2 FOUNDER VARIANTS AND THYROID CANCER RISK

Pamela Brock*¹, Sandya Liyanarachchi¹, Taina Nieminen², Matthew Ringel¹

¹The Ohio State University, USA,²University of Helsinki, Finland

Background: Germline pathogenic variants in CHEK2 are associated with a moderate increase in the lifetime risk for breast cancer. Increased risks for other cancers, including non‐medullary thyroid cancer (NMTC), have also been suggested, although data on lifetime risk estimates are limited. Since CHEK2 is included on almost all germline cancer genetic testing panels, more information about the associated risks is crucial for accurate counseling and risk management.. Up to this point, the data implicating CHEK2 variants in thyroid cancer predisposition primarily derive from Polish cohorts driven by a specific truncating splice site variant (c.444 + 1G>A) with an odds ratio ranging between 6‐10 that appears to be much less common in other populations. In contrast, in non‐Polish populations the c.1100delC and c.470T>C/p.Ile157Thr CHEK2 variants are the predominant variants, reported to represent 61.1% and 63.8% of all CHEK2 pathogenic variants detected in two large commercial laboratory US‐based cancer cohorts. To further delineate the impact of common CHEK2 variants on thyroid cancer, we aimed to investigate the association of these three CHEK2 founder variants (c.444 + 1G>A, c.1100delC, and c.470T>C/p.Ile157Thr) on thyroid cancer susceptibility in three cohorts of unselected patients with non‐medullary thyroid cancer.

Methods: Individuals with NMTC and a founder variant were assessed within three cohorts: (1) 1544 NMTC patients (and 1593 controls) from previously published GWAS analysis, (2) 885 NMTC patients with germline exome sequencing, and (3) 499 NMTC patients with germline sequence data available in The Cancer Genome Atlas (TCGA).

Results: The predominant variant from Polish cohorts (c.444 + 1G>A) was present in only one person (exome cohort). The proportion of patients with c.1100delC was 0.92% in the GWAS cohort, 1.47% in the exome cohort, and 0.80% in the TCGA cohort, respectively. The odds ratios for NMTC associated with c.1100delC within each cohort was 1.71, 2.91, and 1.58, respectively. The proportion of patients with c.470T>C/p.Ile157Thr was 0.91% in the GWAS cohort, 1.01% in the exome cohort, and 0.80% in the TCGA cohort, respectively. The odds ratios for NMTC associated with c.470T>C/p.Ile157Thr within each cohort was 1.73, 2.03, and 1.60, respectively.

Conclusions: Our analyses in cohorts of unselected patients with non‐medullary thyroid cancer suggest that the CHEK2 variants c.1100delC and c.470T>C/p.Ile157Thr have only a modest impact on thyroid cancer risk. These results provide important information for providers regarding the magnitude of thyroid cancer risk associated with these common CHEK2 variants.

POSTER 366

Thyroid Cancer Clinical Poster

CLINICAL IMPACT OF CENTRAL (N1A) AND LATERO‐CERVICAL (N1B) LYMPH NODES METASTASES ON DISEASE SPECIFIC (DSS) AND RECURRENCE FREE (RFS) SURVIVAL IN SPORADIC MEDULLARY THYROID CARCINOMA (MTC) PATIENTS

Antonio Matrone*¹, Alessasndro Prete¹, Carla Gambale¹, Elisa Minaldi¹, Valeria Bottici¹, Gabriele Materazzi², Eleonora Molinaro¹, Liborio Torregrossa³, Rossella Elisei¹

¹University Hospital of Pisa, Department of Clinical and Experimental Medicine, Unit of Endocrinology, Italy,²University Hospital of Pisa, Department of Surgical, Medical, Molecular Pathology and Clinical Area, Unit of Endocrine Surgery, Italy,³University Hospital of Pisa, Department of Surgical, Medical, Molecular Pathology and Clinical Area, Anatomic Pathology Section, Italy

Objective: Distant metastasis at diagnosis is the worst prognostic factor for DSS as far as lymph node metastases both for DSS and RFS in sporadic MTC. The aim of this study is to assess the impact of N1a and N1b, separately evaluated, on DSS and RFS in sporadic MTC.

Methods: We evaluated 674 sporadic MTC patients (2000‐2020), followed at our institution. We excluded patients with distant metastases at diagnosis (60/674–8.9%), those without central and/or latero‐cervical lymph nodes dissection (Nx) (57/614–9.3%) and without controls after surgery (11/614–1.8%). Therefore, we defined 3 groups: 1) N0 (310/546 – 56.8%) without lymph nodes metastases, 2) N1a (105/546 – 19.2%) with metastatic lymph nodes of the central compartment alone, 3) N1b (131‐546 – 24%) with metastatic lymph nodes of the latero‐cervical ± central compartment.

Results: In a median time of 110 months (IQR 60‐164.25) we observed 37 (6.8%) cancer related death (CRD), 5/310 (1.6%) in N0 and 32/131 (24.4%) in N1b; no CRD were observed in N1a group. Kaplan Meier (KM) analysis showed DSS of 100% at 5 and 10 years in N0 and N1a, while 83% and 78% in N1b (p < 0.01). After excluding patients who had structural disease at first post‐operative evaluation (67/546 – 12.3%), we observed 69/479 (14.4%) recurrences in a median follow‐up time of 75 (IQR 32.75‐130) months; 14/308 (4.5%) in N0, 17/99 (17.2%) in N1a and 38/72 (52.8%) in N1b group. RFS was 99% and 97% in N0, 87% and 82% in N1a and 58% and 48% in N1b group, at 5 and 10 years respectively (p < 0.01). Also, comparing N0 and N1a (p < 0.01) and N1a and N1b (p < 0.01) a difference in RFS was observed.

Conclusions: In our series of sporadic MTC without distant metastases at diagnosis, regardless of other risk factors, N1b at diagnosis was a negative prognostic factor for DSS and RFS. Conversely, N1a alone, regardless of number and dimension of the metastatic lymph nodes, had no impact on DSS as far as N0. However, N1a patients should be monitored for recurrence, since they showed a risk significantly higher than N0, but lower than N1b, of having structural recurrence over time.

POSTER 367

Thyroid Cancer Clinical Poster

RECURRENT OR PERSISTENT THYROID CARCINOMA IN THE PEDIATRIC POPULATION AFTER RADIOACTIVE IODINE TREATMENT: A SYSTEMATIC REVIEW AND META‐ANALYSIS

Eric Pineda*¹, Alyssa Webster¹, Dylan Pinion¹, Mohammad Hussein², Eman Toraih², Emad Kandil²

¹Tulane University School of Medicine, USA,²Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, USA

Objective: The rates of recurrence in differentiated thyroid carcinoma in the pediatric population is not well understood. Radioactive iodine (RAI) therapy is a widely accepted treatment modality that has been shown to increase disease‐free survival. There is a paucity of data around the efficacy of RAI therapy in children. This study aims to understand the rates of recurrence or persistence in patients receiving RAI therapy post‐surgery.

Methods: A systematic review was conducted searching for articles published in 2000 to April 2023. Articles describing recurrent or persistent DTC in patients (age ≤21) were included. Pooled proportions were estimated using Arcsine transformation and Inverse variance method. Patients with and without RAI were compared. Relative risk for developing recurrence/persistent disease was estimated under fixed‐effects model using Mantel‐Haenszel method and DerSimonian‐Laird estimator.

Results: This study included 15 articles. The sample size consisted of 1477 patients. mean age was 14.9 years (95%CI = 14.1‐15.7) and 23% were males. Of which 1162 (79%) underwent RAI therapy and 315 (21%) did not. Among patients who received RAI therapy, 238 (20%) had recurrent/persistent disease and 828 (70%) reported no evidence of recurrence. In patients who did not receive RAI therapy, 51 (16%) had recurrent/persistent disease and 216 (69%) reported no evidence of recurrence. Patients who received RAI were less likely to develop recurrence (RR = 0.62, 95%CI = 0.37‐1.02, I² = 35%).

Conclusion: A significant proportion of the pediatric population receive RAI therapy despite short and long term side effects. A portion of these patients still suffer from recurrent or persistent disease despite therapies. More should be done to investigate other risk factors that may portend to recurrent or persistent disease.

POSTER 368

Thyroid Cancer Clinical Poster

CHARTING SPATIAL TRANSCRIPTOMIC AND PROTEOMIC MAP FOR NODAL METASTASIS

Eman Toraih*^1,2, Mohamed Hussein¹, Jessan Jishu¹, Manal Fawzy², Emad Kandil¹

¹Tulane University School of Medicine, USA,²Suez Canal University, Egypt

Background: Detecting nodal metastasis remains a challenge since current imaging techniques, biochemical analysis, and genomic screening cannot describe tumor heterogeneity or predict progression. Up to 30% of thyroid cancer (TC) patients undergoing surveillance develop progressive cancer requiring aggressive surgical intervention, leading to a mortality rate greater than 60%. Delayed surgical management may increase morbidity, cost, and undue risk. Thus, there is an urgent need to identify reliable omics‐driven biomarkers for early detection of tumors with lymph node metastasis (LNM) to improve decision‐making regarding management and follow‐up care for patients of various demographics.

Objective: Preliminary data revealed a prognostic panel of aggressive features within accessible chromatin regions under active regulatory elements. We propose to develop a test to predict LNM that can rapidly translate into clinical studies. We hypothesize that defined gene regulatory networks delineate the presence of intratumor aggressive clones which promote aggressive behavior. Deciphering the spatial structure of the tumor microenvironment will facilitate identifying predictive markers in autoimmune diseases.

Methods: Multi‐omics and miRNA‐seq analysis of primary and metastatic thyroid tissues were used to characterize tumor ecosystems in TC patients with and without Hashimoto's thyroiditis and BRAF mutation. GeoMx digital spatial transcriptomic and proteomic profiling was employed for spatial mapping of the candidate markers. Quantitative in situ biomarker analysis was performed using RNAscope HiPlex hybridization at cellular resolution. BRAF mutation detection using BaseScope delineated subclonal evolution leading to metastasis. HALO image software was used for analysis.

Results: We identified genetic regulatory networks driving tumorigenesis and progression enclosing 2 microRNAs and 12 gene markers. Of these, FN1, KRT19, and LGALS3 were upregulated in N1 and had an intermediate level in N0 compared to normal thyroid tissue in both tumor‐ and immune cell‐enriched compartments. Nuclear localization of BRAFV600E was associated with poor prognosis. A refined deep‐learning model and predictive nomogram were generated for tracking cancer progression.

Conclusion: Results using the validated triple biomarker test and point‐of‐care predictive tool for various patient demographics and comorbidities showed high accuracy for risk stratification, unraveling the test as one that fits all. This can help monitor patients for evidence of progression in prospective clinical trials.

POSTER 370

Thyroid Cancer Clinical Poster

COMPARISION BETWEEN GROUPS ACCORDING TO SUBTYPES IN PAPILLARY THYROID CANCER

Jun Sung Lee*, Jin Seok Lee, Hyeok Jun Yun, Hojin Chang, Seok‐Mo Kim, Yong Sang Lee, Hang‐Seok Chang

Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Korea, Republic of

Background: There are several subtypes of thyroid cancer, each of which is divided into aggressive and non‐aggressive. In this study, we plan to study what clinical features are obtained when these subtypes and conventional type are present at the same patient.

Methods: From March 2009 to December 2021, we retrospectively compared 26,449 patietns into five groups according to subtypes of papillary thyroid cancer (Conventional, Aggressive, Non‐aggressive, Conventional + Aggressive, Conventional + Non‐aggressive). We investigated patient characteristics and clinical features.

Results: There was a significance difference according to the subtypes of PTC. Aggressive group had more aggressive clincal features than conventional group, and also conventional group than Non‐aggressive group. If each group had a conventional type together, each group's clinical features tended to be closer to the conventional type than the original group.

Conclusions: In the comparison between groups according to subtypes in papillary thyroid cancer, the aggressiveness of each group was intensified in the following order. ( Aggressive > Conventional + Aggressive

POSTER 371

Thyroid Cancer Clinical Poster

HEALTH‐RELATED QUALITY OF LIFE ASSOCIATIONS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AFTER RADIOACTIVE IODINE TREATMENT: A CROSS‐SECTIONAL STUDY

Alaina Carr*, Gautham Pillai, Jacqueline Jonklaas, Gary Bloom, Kristi Graves

Georgetown University, USA

Objective: To evaluate associations between patient‐reported symptom burden, distress, and perceived self‐efficacy of patients with differentiated thyroid cancer (DTC) after radioactive iodine (RAI) treatment with patient health‐related quality of life (HRQoL).

Methods: Sixty‐nine participants diagnosed with DTC who underwent RAI treatment within the past three years completed a cross‐sectional online survey disseminated by ThyCa members. Measures included symptom burden (oral mucositis, measured with the PROMS¹; and salivary, lacrimal, and nasal symptoms, measured with the SALANS²), distress (NCCN distress thermometer³), perceived coping self‐efficacy (CBI‐B⁴), and HRQoL (FACT‐G7⁵). Pearson correlations assessed the relationships between demographics, clinical characteristics, and HRQoL. Hierarchical multiple linear regression models evaluated the associations between patient‐reported symptom burden, perceived self‐efficacy, distress, and HRQoL, controlling for relevant demographic (age, gender, marital status, education, race, and ethnicity) and clinical variables (stage, time since diagnosis and RAI treatment).

Results: Participants (N = 69) had a mean age of 41.1 (SD = 14.4) years and were, on average, 1.6 (SD = 0.77) years from the time of diagnosis and 1.12 (SD = 0.78) years since RAI treatment. Most participants identified as female (88.4%), married or partnered (78.5%), and received a college or graduate degree (72.7%); 18.8% identified as Hispanic, 21.7% identified as non‐White and about half were employed full‐time (49.3%). HRQoL was unrelated to age, marital status, time since DTC diagnosis, and time since RAI treatment. Non‐White race, Hispanic ethnicity, and lower educational background were associated with lower HRQoL scores, respectively (r = ‐.25, p < .04; r = ‐.25, p < .05; r = ‐.27, p < .05). The overall hierarchical multiple linear regression model was significant (F = 6.40, p = .001), accounting for 69.2% of the variance. Worse overall RAI symptoms (β = ‐.10, p = 001), higher distress (β = ‐.74, p = .007), and lower perceived coping self‐efficacy (β = .14, p = .01) all were significantly associated with lower overall HRQoL. Oral mucositis symptoms were unrelated to HRQoL.

Discussion/Conclusion: Lower HRQoL was associated with worse RAI symptoms, distress, and lower coping self‐efficacy. In contrast, age, disease stage, and time since diagnosis or RAI treatment were unrelated to HRQoL. Results highlight the need to understand and address symptom burden among patients with DTC post RAI. Future work can develop an informational support intervention for patients' self‐management of RAI symptoms.

POSTER 372

Thyroid Cancer Clinical Poster

THYROID CANCER INCIDENCE IN NEW MEXICO AMERICAN INDIANS, HISPANICS AND NON‐HISPANIC WHITES, 1992‐2019

Jordan West*¹, Brianne Wiemann², Garth Olson², Angela Meisner³, Charles Wiggins⁴, Nathan Boyd²

¹University of New Mexico School of Medicine, USA,²University of New Mexico Department of Surgery, USA,³UNM Health Sciences New Mexico Tumor Registry, USA,⁴University of New Mexico Department of Internal Medicine, Division of Epidemiology, USA

Purpose: The incidence of thyroid cancer across gender and race/ethnicity in the United States has been rising since the 1970s. However, there is a paucity of published data regarding the incidence of thyroid cancer in the New Mexican (NM) population. We hypothesize that due to NM's unique and prevalent barriers to healthcare, the incidence of thyroid cancer in this state will vary from that demonstrated on a national level.

Methods: Patients were queried from the New Mexico Tumor Registry (NMTR) to include all NM residents diagnosed with thyroid cancer between 1992‐2019. For 2010‐2019, age‐adjusted incidence rates were calculated via direct method using the 2000 United States population as the adjustment standard. Differences in incidence rate by race/ethnicity were assessed with rate ratios between groups. For 1992‐2019, temporal trends in age‐adjusted incidence rates for three major race/ethnic groups in NM [Non‐Hispanic White (NHW), Hispanic, and American Indian (AI)] were assessed by joinpoint regression using National Cancer Institute software.

Results: Our study included 3,161 patients for the time period 2010‐2019, including NHW (1518), Hispanic (1425), and AI (218) cases. Incidence of thyroid cancer among NHWs was similar to what was seen at the national level. Females had higher annual age‐adjusted incidence rates than males in each racial/ethnic category. The AI population had lower incidence rates than NHW and Hispanics from 1992‐2019. Incidence of thyroid cancer among Hispanics and AIs had linear increases with positive APCs over the entire study period. The Hispanic female population had the highest incidence and significant APC overall. Incidence rates increased among all groups during from 1992‐2019, but the patterns of change varied among the group.

Conclusion: After subgroup analysis based on age and sex, race and ethnicity in NM is associated with trends in incidence significantly different from those at a national level. The national change of thyroid cancer is not reflected in the NM population evaluated in this study.

POSTER 373

Thyroid Cancer Clinical

INTRATHYROIDAL METASTASIS PREDICTS LYMPH NODE METASTASIS AND IMPAIRS PATIENTS' SURVIVAL IN PAPILLARY THYROID CARCINOMA

Ming Xu*, Zihan Xi, Jie Ming, Tao Huang

Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China

Objective: Intrathyroidal metastasis (ITM) is a rare pathologic pattern of papillary thyroid carcinoma in a series of case reports. Whether or not ITM is an independent pathological subtype other than multifocality is still unknown. There is very little research focusing on its clinical characteristic and effects on patients' prognosis or comparing it with multifocality.

Methods: In this work, we retrospectively inspected 10816 patients having surgeries in our center from 2014 to 2020. We divided all patients into two categories: patients with intrathyroidal metastasis (ITM) and patients without intrathyroidal metastasis (NITM). Clinical characteristics including age, gender, surgery extent, the maximum diameter of the main tumor, multifocality, and infiltration were all analyzed. Besides, we compared the proportion, number and extent of lymph node metastasis in ITM and NITM patients. Propensity score matching was used to filter patients with similar baselines and Kaplan‐Meier analysis and cox regression were conducted in 344 patients after propensity score matching.

Results: Intrathyroidal metastasis was significantly related to worse patterns of papillary thyroid cancer such as male, larger diameter, multifocality, and extrathyroidal extension. In the analysis of lymph node metastasis, we found that intrathyroidal metastasis is an independent predictor of both cervical and lateral lymph node metastasis. The larger proportion of patients with lymph node metastasis (86.6% vs 48.0%, p < 0.001), the greater number of metastasized lymph nodes (8.78 vs 4.24, p < 0.001), and the extensive region of lymph node metastasis (84.6% vs 46.5%, p < 0.001 in cervical lymph nodes and 49.9% vs 11.6%, p < 0.001 in lateral lymph nodes) were all presented in ITM than NITM. In survival analysis, ITM showed poorer recurrence‐free survival (p < 0.0001) and independent predictive effect in multivariate cox regression (HR = 10.51, 95% CI: 3.35‐32.97, p < 0.0001).

Discussion/Conclusion

Intrathyroidal metastasis, as a rarely seen feature in papillary thyroid cancer, is a risk factor for lymph node metastasis and poor survival. Deeper attention is needed to define this feature and promote precision diagnosis and treatments.

POSTER 374

Thyroid Cancer Clinical Poster

PREOPERATIVE LYMPH NODE METASTASIS PREDICTION MODEL FOR PAPILLARY THYROID MICROCARCINOMA

Si‐Ying Lin*, Bo Wang

Fujian Medical University Union Hospital, China

Objective: To analyze the risk factors for lymph node metastasis in PTMC and establish a predictive model.

Methods: From 2020 to 2021, the data of 1006 patients with PTMC in our hospital were analyzed. Risk factors were analyzed in binary logistic regression, and the nomogram model was further established.

Result: Of 1006 patients with PTMC, 531 (52.8%) had lymph node metastasis. Logistic regression of the training set showed that male sex, maximum diameter >0.665 cm, the distance between nodule and capsule ≤1 mm, microcalcification, ultrasound findings of bilateral suspicious lesions, and age ≤45.5 years were risk factors for lymph node metastasis. A nomogram was constructed, and AUCs of 0.718 and 0.708 in the training and validation sets, respectively, were drawn; the clinical decision curve shows that the model has a high net return rate in the range of threshold probability of 10%‐90%. The lymph node metastasis rates of the groups with minimal distances between the nodule and capsule less than 1 mm, 2 mm, and 3 mm were 67.5%, 15.2%, and 9.8%, respectively. Among the tumors close to the capsule, the lymph node metastasis rates of the nodes with no contact and contact of the capsule less than 1 mm and 2 mm were 46.19%, 74.14%, and 80.77%, respectively.

Conclusion: We successfully established a preoperative LNM prediction model for PTMC. Logistic regression showed that male sex, maximum diameter >0.665 cm, the distance between nodule and capsule ≤1 mm, microcalcification, suspected lesions on both sides and age <45.5 years were risk factors for lymph node metastasis. The closer or longer the thyroid capsule is, the higher the rate of lymph node metastasis.

POSTER 375

Thyroid Cancer Clinical Poster

THE CLINICAL PREDICTIVE VALUE OF PREOPERATIVE THYROGLOBULIN ANTIBODY FOR PAPILLARY THYROID CARCINOMA

Zhuyao Li¹, Linshi Zhang*², Meng Jia¹, Ping Wang², Xiubo Lu¹

¹The First Affiliated Hospital of Zhengzhou University, China,²the second affiliated hospital of Zhejiang Univiersity, China

Objective Thyroglobulin antibody (TgAb) is a class G immunoglobulin and has been identified as a conventional marker for thyroid autoimmunity, while the relationship between thyroid autoimmunity and thyroid cancer still remains controversial. This study was to explore the effect of thyroglobulin antibody on the prognosis of papillary thyroid carcinoma patients.

Methods The clinicopathological data such as lymph node metastasis, tumor size, multifocality, bilaterality, extrathyroidal extension and TNM stage of 979 patients with thyroid papillary carcinoma from September 2011 to December 2021 in the First Affiliated Hospital of Zhengzhou University and the Second Affiliated Hospital of Zhejinag University were retrospectively collected and divided into two groups according to the level of thyroglobulin antibody. Then the statistical methods were used to analyze the value of preoperative thyroglobulin antibody on the prognosis of thyroid papillary carcinoma.

Results Compared with the negative thyroglobulin antibody group, the positive group had a higher rate of lymph node metastasis (32.7% V.S. 22.3%, p = 0.004), more metastasis lymph node (1.4 ± 2.7 V.S. 0.9 ± 2.5, p = 0.020) and higher TNM stage (p = 0.000), however, there was no significant difference in multifocal (p = 0.533), bilaterality (p = 0.433), extrathyroidal extension (p = 0.781), tumor size (p = 0.441) and thyroid function (FT3: p = 0.602; FT4: p = 0.455; TSH: p = 0.766).

Conclusion Preoperative positive thyroglobulin antibody is closely related to lymph node metastasis of papillary thyroid carcinoma. The rate and the number of metastasized lymph node were significantly increased in patients with high level of TgAb. Therefore, it is suggested that preoperative high level thyroglobulin antibody might provide a certain reference to predict the aggressiveness tumor characteristics of thyroid cancer patients.

POSTER 376

Thyroid Cancer Clinical Poster

CLINICAL SIGNIFICANCE OF TUMOR SIZE IN GROSS EXTRATHYROIDAL EXTENSION TO STRAP MUSCLES (T3B) IN PAPILLARY THYROID CARCINOMA

Joonseon Park, Ja Sung Bae*, Kwangsoon Kim, Jeongsoo Kim

College of Medicine, The Catholic University of Korea, Korea, Republic of

Objective: It has been studied that a larger tumor size in T3b has a worse prognosis than T3b with a smaller tumor size. The present study aims to compare the clinicopathological characteristics among modified T categories and clarify the significance of tumor size in T3b on the DSS of differentiated thyroid carcinoma(DTC).

Methods: A total of 6282 patients with DTC who underwent thyroid surgery at a single center were retrospectively analyzed. Patients with T1, T2, T3a, and T3b categories were included according to the 8th edition of the AJCC/UICC TNM staging system. In the modified T categories, T3b was divided into T3b‐1 (≤2cm) and T3b‐2 (2–4 cm), and T3b‐3 (> 4cm). Disease‐free survival (DFS) and Disease‐specific survival(DSS) were compared among all T categories.

Results: In the total cohort of 6282 patients, T1, T2, T3a, T3b‐1, T3b‐2, and T3b‐3 were 3353 (88.1%), 339 (5.4%), 39 (0.9%), 239 (3.8%), 90 (1.4%), and 20 (0.3%), respectively. There were no differences in DSS between T1 and T3b‐1 (p = 0.319). However, there were significant differences in DSS between T2 and T3b‐2, and between T3a and T3b‐3 (p < 0.001, p = 0.001, respectively).

Conclusions: These results indicate that the tumor size of T3b may affect DSS, which decides AJCC/UICC TNM staging system. T3b(≤2cm) showed no significant difference in mortality compared to T1. A modified stage that moves T3b(≤2cm) to T1 and includes only T3b(>2cm) to T3b may show more efficient performance than the current stage.

POSTER 377

Thyroid Cancer Clinical Poster

Outcome of reoperation for recurrent or persistent papillary thyroid carcinoma: MRI added to ultrasound guided neck dissection

Zimei Tang*, Jie Liu, Jie Ming

Wuhan Union Hospital, China

Background: Cervical Lymph nodes (LNs) are the most common site of papillary thyroid carcinoma (PTC) recurrence. Therapeutic neck dissection (ND) is indicated in patients with PTC who present with imaging and/or pathological evidence of lymph node metastasis (LNM), but the extent of ND remains controversial. Studies have shown that ultrasound (US) may underestimate the extent of actual neck nodal involvement. Thus, a more accurate noninvasive imaging approach for staging PTC is needed. Adding MRI to US for preoperative imaging in ND may improve the outcome of neck reoperation.

Methods: This retrospective cohort study included 304 patients who underwent reoperation for recurrent/persistent PTC from January 2016 to December 2021. Patients were divided into US cohort (n = 228) and US+MRI cohort (n = 76) based on preoperative imaging examinations. We compared the extent of ND in two cohorts and analyzed the results of pathological and preoperative imaging examinations in US+MRI cohort. Outcome of reoperation was measured using biochemical response and the response to therapy classification.

Results: Compared to US cohort, US+MRI cohort tended to undergo central neck dissection (p = 0.009) and had a higher number of (metastatic) LNs removed in the lateral compartment (p < 0.001). In the level‐by‐level analysis, 233 of 489 levels were pathologically proven to be malignant. MRI added to US showed higher sensitivity in level II, V, and VI, and its detection of central LNM increased from 52.5% to 90.9% than US alone (p < 0.001). Excellent response was achieved in more patients at reoperations guided by MRI added to US than US alone in the first assessment (46% vs. 28%) and the last assessment (49% vs. 34%).

Conclusion: MRI shows a good diagnostic value for PTC LNM. MRI added to US helps to determine the extent of neck nodal involvement, especially in the central compartment. After reoperation, more patients with recurrent/persistent PTC who had US+MRI achieved low Tg level and excellent response than those who had US alone, with the removal of a higher number of (metastatic) LNs.

POSTER 378

Thyroid Cancer Clinical Poster

EFFECTS OF NEOADJUVANT CHEMORADIOTHERAPY ON ANAPLASTIC THYROID CARCINOMA: A SINGLE‐CENTER EXPERIENCE

Jin Seok Lee*¹, Jun Sung Lee¹, Hojung Jeong¹, Hyeok Jun Yun¹, Hojin Chang¹, Seok Mo Kim¹, Yong Sang Lee¹, Hang‐Seok Chang¹, Cheong Soo Park²

¹Gangnam Severance Hospital, Korea, Republic of,²CHA ilsan medical center, Korea, Republic of

Objective: Anaplastic thyroid carcinoma (ATC) is associated with the highest mortality risk of any thyroid‐arising tumor; however, there is currently no effective therapy for ATC, and multimodal therapy is associated with a relatively high mortality risk. Here, we investigated the effects of neoadjuvant chemoradiotherapy on patients with ATC treated with paclitaxel and intensity‐modulated radiation therapy (IMRT).

Methods: The medical records of 157 patients with ATC at Gangnam Severance Hospital were reviewed between January 2016 and November 2022. Only nine patients were eligible for surgery after neoadjuvant chemoradiotherapy according to the Gangnam Severance Hospital protocol for ATC.

Results: Seven patients were female, and two were male. The median age of the patients was 62 years (range: 53–76 years). The median tumor size of the patients was 3.94 cm (range: 2.1–5.6 cm). All the patients were treated with neoadjuvant paclitaxel and concomitant IMRT. The median number of cycles of neoadjuvant paclitaxel was 5 (range: 2–6 cycles) and the median IMRT dose was 5680 cGy (range: 5250–6600 cGy). Six patients showed a reduction in tumor size after neoadjuvant chemoradiotherapy. Three patients showed no significant differences or increases in tumor size after neoadjuvant chemoradiotherapy, but did display eminent tumor necrosis. Of the six patients with initial regional node metastasis, four showed a decrease in the size of metastatic nodes and internal necrosis. One patient had initial distant metastasis in the lung, and another showed newly diagnosed lung metastasis after neoadjuvant therapy. The mean interval from neoadjuvant radiation therapy to surgery was 93 days (range: 14–170 days). The median survival of patients with ATC who received neoadjuvant chemoradiotherapy was 358 days (range: 123–2,023 days).

Conclusion: Effective neoadjuvant chemoradiotherapy followed by complete surgical resection could be considered as one of the treatment options with prolonged median survival and safe local progression control.

POSTER 379

Thyroid Hormone Action Metabolism and Regulation Basic Poster

THE RELATIONSHIP BETWEEN THYROID FUNCTION WITH ATHEROSCLEROSIS IN PATIENTS WITH TYPE 2 DIABETES AND DIFFERENT THYROID PEROXIDASE ANTIBODY LEVELS

Wenwen Gao, Xing Qian*

The First Affiliated Hospital of Dalian Medical University, China

Objective: To clarify the association between thyroid function with atherosclerosis in patients with type 2 diabetes who had different TPOAb levels could take better strategies for early prevention and treatment of macroangiopathy and related thyroid screening in patients with T2DM.

Methods: 839 patients with type 2 diabetes aged between 18 and 75 years were hospitalized in Endocrinology ward at the First Affiliated Hospital of Dalian Medical University from January 2017 to December 2019. According to the levels of serum TPOAb(TPOAb >60 IU/ml or ≤60 IU/ml)and normal (0.38‐4.34 μIU/ml) or increased (>4.34 μIU/ml) levels of serum thyroid stimulating hormone (TSH), total patients were divided into four groups: ① TPOAb‐negative group with normal thyroid function; ② TPOAb‐negative group with SCH; ③ TPOAb‐positive group with normal thyroid function; ④ TPOAb‐positive group with SCH.

Results: Patients with T2DM and SCH have significantly lower serum FT3 levels and significantly higher TC and LDL‐C when their TPOAb is positive. Serum FT3 levels within normal range is negatively correlated with carotid plaque. Lower serum FT3 levels within the normal range are a risk factor for carotid plaque. Serum TSH, TC levels and the ratio of CIMT thickening in TPOAb‐positive T2DM patients are increased compared with TPOAb‐negative patients while serum FT3 levels are decreased. TPOAb‐positive was positively correlated with CIMT thickening and was an independent risk factor of CIMT thickening

Conclusions: T2DM patients with positive TPOAb may prone to triger the formation of carotid plaques by affecting the level of FT3. TPOAb may be an independent risk factor for CIMT thickening.

POSTER 380

Thyroid Hormone Action Metabolism and Regulation Case Study Poster

A CASE OF CHORIOCARCINOMA‐MEDIATED HYPERTHYROIDISM

David Berger*, Jimmy Vo, Maria Pagan, Jiali Fang, Hoang‐Long Huynh, Susana Ebner

Columbia University Irving Medical Center, USA

A 31 year‐old man with past medical history of asthma and no family history of thyroid disease presented to the emergency department with shortness of breath. On arrival, the patient was febrile, tachycardic, and hypoxic. Physical exam showed no goiter and no thyroid eye disease. Computed Tomography of the Chest with intravenous contrast showed innumerate pulmonary lesions with mediastinal lymphadenopathy, and a normal thyroid gland; a scrotal ultrasound showed multiple hypoechoic lesions in the right testicle. A TSH was 0.01 mIU/L, a free T4 was 2.53 ng/dL, a total T4 was 23.24 ug/dL, and a total T3 was 372.7 ng/dL. TSH‐Receptor antibody and thyroid‐stimulating immunoglobulin were negative. The patient was initially managed symptomatically with beta‐blockade but developed worsening thyrotoxicosis. A beta‐HCG was checked which was 876,190 miU/mL, and the patient was diagnosed with metastatic testicular choriocarcinoma. The patient was started on methimazole at increasing doses, and chemotherapy with cisplatin and etoposide was initiated. The patient's course was complicated by acute respiratory distress syndrome, kidney failure, and vasodilatory shock following the first cycle of chemotherapy, from which patient required tracheostomy but had recovered renal function. Two weeks after chemotherapy and methimazole initiation, thyroid function normalized and methimazole was gradually tapered. Seven weeks after initiation of chemotherapy, the patient's beta‐HCG had dropped to 8,393 mIU/mL; patient briefly was hypothyroid but had thyroid function recover after a short course of levothyroxine.

HCG‐mediated thyrotoxicosis is a rare complication of choriocarcinoma; a review of 144 cases of choriocarcinoma showed that 3.5% of patients with this germ‐cell tumor develop thyrotoxicosis. The mechanism of this thyrotoxicosis is due to a homology between TSH and the beta‐HCG that can be produced by the tumors, leading to thyroid stimulation and production of thyroid hormone. Patients typically develop signs of thyrotoxicosis if a serum beta‐HCG is >50,000 mIU/mL. Resolution of the thyrotoxicosis usually occurs as the malignancy is treated and the burden of beta‐HCG producing tumor is reduced. In this case, we were able to manage the patient's thyrotoxicosis with thionamides until the chemotherapy was able to exert its cytotoxic effect on the malignancy.

POSTER 381

WITHDRAWN

POSTER 382

Thyroid Hormone Action Metabolism and Regulation Clinical Poster

NORMALIZATION OF SERUM TSH LEVELS IN PATIENTS TREATED WITH ENTERIC LT‐4 MALABSORPTION, AFTER THE SWITCH FROM ORAL TABLET L‐THYROXINE (L‐T4) TO THE LIQUID FORMULATION

Poupak Fallahi*¹, Silvia Martina Ferrari², Giusy Elia³, Francesca Ragusa³, Armando Patrizio⁴, Sabrina Rosaria Paparo¹, Eugenia Balestri³, Chiara Botrini³, Valeria Mazzi³, Alessandro Antonelli³

¹Department of Translational Research of New Technologies in Medicine and Surgery, University of Pisa, Italy,²Department of Clinical and Experimental Medicine, University of Pisa, Italy,³Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Italy,⁴Department of Emergency Medicine, Azienda Ospedaliero‐Universitaria Pisana, Italy

Objective: Many different factors interfere with the absorption of L‐thyroxine (L‐T4). Recently it has been showed that patients with enteric diseases (ED) such as ulcerative colitis, Crohn disease, colectomy performed for different disorders, can suffer from L‐T4 tablets malabsorption.

Methods: Thirty‐five patients, who received L‐T4 in the tablet formulation with ED and reported elevated serum thyroid‐stimulating hormone (TSH) levels, were enrolled and switched to the oral liquid L‐T4 formulation at the same dose.

Results: After the switch to the L‐T4 liquid formulation (at the same tablet dose), a normalization, or reduction, of circulating TSH levels was reported. Furthermore, ten patients were switched again to L‐T4 in tablets (at the same dosage) for different reasons, and TSH levels got worse (reaching the hypothyroid range).

Conclusion: We demonstrate that the use of L‐T4 liquid formulation can overcome the problem of the LT‐4 absorption impairment in ED. Additional studies are necessary to evaluate the liquid L‐T4 formulation also in other conditions of altered L‐T4 absorption.

POSTER 383

Thyroid Hormone Action Metabolism and Regulation Clinical Poster

DECREASED SENSITIVITY TO THYROID HORMONES IS A PROTECTIVE ADAPTATION AGAINST THE RISK OF DEVELOPING CARDIOVASCULAR DISEASE IN THE ELDERLY POPULATION

Lei Zhao*, Min Zhao

The first hospital of China Medical University, China

Objective: Thyroid hormone has many effects on the heart and vascular system. There is a delicate interplay among thyroid hormones, thyrotropin (TSH), metabolic homeostasis and cardiovascular disease. However, the association between thyroid hormone sensitivity and metabolic and cardiovascular indices has not been elucidated in elderly population.

Methods: This study enrolled 11,701 participants (male 5348, female 6353). Metabolic indices (body mass index [BMI], serum uric acid [sUA], plasma glucose and lipoprotein) were measured. cardiovascular indices (ECG, plasma CK‐MB and NT‐proBNP) were evaluated. The thyroid hormone sensitivity indices which include feedback quantile‐based index (TFQI). Higher thyroid feedback quantile‐based index (TFQI) quartiles indicated lower thyroid hormone sensitivity. The 10% FRS (Framingham risk score) were calculated. The relationship between thyroid hormone sensitivity indices and metabolic indices and cardiovascular disease (CVD) risk were calculated.

Result: Participants with decreased sensitivity to thyroid hormone had lower BMI, TC, TG, LDL, CK‐MB and higher sUA levels. Ageing is negatively associated with TFQI (R2 = ‐0.1, p = 0.01). In adults (age <60), the prevalence of NAFLD was significantly less frequent in the Q4 group of TFQI (OR 0.846, 95%CI 0.719‐0.995). In elderly population, sensitivity to thyroid hormones(Q4) was an independent predictor for lower prevalence of metabolism disorder (OR 1.637, 95%CI 1.199‐2.236). However, in elderly participants lower sensitivity to thyroid hormones(Q4) predict a lower prevalence of abnormal ST segment (OR 0.406, 95%CI 0.22‐0.75) and a lower incidence of FRS >10% (OR 0.631, 95%CI 0.522‐0.762).

Conclusion: In conclusion, the results suggests that in the elderly population, lower sensitivity to thyroid hormones may be a protective adaptation against the risk of developing cardiovascular disease, as indicated by a lower prevalence of abnormal ST segment and a lower incidence of FRS >10%.

POSTER 384

Thyroid Imaging Basic Poster

A THYROID 3D RECONSTRUCTION AND VISUALIZATION SYSTEM BASED ON B‐MODE 2D ULTRASOUND

Jiayu Zhu*¹, Yifei Lv², Mingbo Zhang³, Junchen Wang¹

¹Beihang University, China,²Tsinghua University, China,³the first medical center, general hospital of Chinese PLA, China

Objective: Thyroid ultrasonography (TUS) is a highly sensitive and available safe imaging technology that is harmless to patients in clinical thyroid diagnosis. As one of the most commonly used image modality, B‐mode 2D ultrasounds only show the sections of tissues while losing a lot of 3D information such as the volume of the thyroid, 3D relative position between the thyroid and the surrounding tissues etc. To overcome these limitations, we developed a real‐time 2D to 3D US image reconstruction system.

Methods: The real‐time 3D image reconstruction method is combined with Bezier interpolation and pixel nearest neighbor interpolation (PNN) algorithm. The system conducted the visualization of reconstructed results by volume rendering. This system also provided interactive functions that clinicians can freely select regions of interest and segment or adjust the 3D images.

Results: The performance of the proposed 3D reconstruction algorithm is defined by the registration error between the reconstruction result and the actual geometry. We assessed the reconstruction performance on a femur and a trachea model with known 3D information. The experiments indicated that when the reconstruction the voxel size was set to be (0.5^3 mm^3, 1.0^3 mm^3, 1.5^3 mm^3), the reconstruction errors of the femur and trachea model were (0.23 mm, 0.31 mm, 0.56 mm) and (0.62 mm, 0.88 mm, 1.41 mm), respectively.

To determine the clinical practicality of this system, 2 sonographers examined the thyroids of 6 human volunteers with the assist of this 3D reconstruction system. Thyroids with surrounding tissues were reconstructed into 3D image and three of the volunteers with 3‐4cm thyroid nodules were detected.

Conclusion: The 3D real‐time reconstruction enables 3D ultrasound imaging of the thyroid and its internal nodules, which is accepted by the sonographers. It is expected that the reconstruction result can help measure the volume of the thyroid and thyroid nodules as well as help with the surgical planning and navigation.

POSTER 385

Thyroid Imaging Clinical Poster

EVALUATION OF LEARNING METHODS SIMILAR TO DEEP LEARNING AND DEVICE USING DEEP LEARNING FOR THE DIAGNOSIS OF THYROID NODULES

Daham Kim*¹, Yoon‐a Hwang¹, Youngsook Kim¹, Hye Sun Lee², Eunjung Lee³, Jin Young Kwak⁴

¹Department of Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Korea, Republic of,²Biostatistics Collaboration Unit, Yonsei University College of Medicine, Korea, Republic of,³School of Mathematics and Computing (Computational Science and Engineering), Yonsei University, Korea, Republic of,⁴Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Korea, Republic of

Objective: We recently developed a deep convolutional neural network algorithm (SEveRance Artificial intelligence program, SERA) using 13,560 ultrasonography images of thyroid nodules labeled benign and malignant and this algorithm showed comparable diagnostic performance with experienced radiologists. We wondered whether this self‐learning method of SERA could be adapted for human learning as an ancillary approach to man‐to‐man training.

Methods: Twenty‐one internal medicine residents studied the “learning set” in three replicates which was composed of 3,000 images of selected from 13,560 thyroid nodules and their diagnostic performances were evaluated before study and after every learning session using the “test set” which was composed of 120 thyroid nodule images. The diagnostic performances of eight radiology residents were evaluated before and after man‐to‐man training using the same “test set”. After final test, all readers once again evaluated the “test set” with the assistance of SERA.

Results: Before study, the mean area under the receiver operating characteristic (AUROC) of internal medicine residents were considerably lower than that of radiology residents (0.578 and 0.701, respectively). Diagnostic performance of internal medicine residents, although not as much as radiology residents who received man‐to‐man training (AUROC = 0.735), increased over the course of the learning program (AUROC = 0.665, 0.689, and 0.709, respectively). All diagnostic performances of internal medicine residents and radiology residents were better with the assistance of SERA (AUROC 0.755 and 0.768, respectively).

Conclusion: A novel iterative learning method using selected ultrasound images from big data sets can help beginners learn to differentiate between benign and malignant thyroid nodules. With the assistance of SERA, the diagnostic performances of readers with various experiences in thyroid imaging could be further improved.

POSTER 386

WITHDRAWN

POSTER 387

Thyroid Nodules and Goiter Case Study Poster

THYROID NODULE RUPTURES: COULD ELECTRODE SIZE MAKE A DIFFERENCE?

Crystal Acosta*, Niketa Kalara, Daniela Bignoli, Estefania Cecilio, Agustin Andrade

Mount Sinai Medical Center, USA

Nodular goiter is one of the most common benign lesions of the thyroid, traditionally treated with surgical resection. Radiofrequency ablation (RFA) is a minimally invasive technique that can be used to reduce the size of these nodules and is relatively safe, with a complication rate of about 3.3%. The most common complications are pain during the procedure, voice changes, and hematomas. Nodule ruptures occur in 0.2% of RFA cases. Nodule ruptures present as sudden neck pain, erythema, and bulging and is thought to be due to volume expansion caused by delayed hemorrhage. We present 2 cases of nodule ruptures that occurred after using a 17 gauge electrode.

The first case was a 69 year‐old male with incidentally found thyroid nodules. Ultrasound showed a right nodule of 4.5x4.8 cm. Fine needle aspiration (FNA) was negative and RFA was performed. Sixty‐two days later, the patient developed sudden onset neck pain and swelling of the right thyroid and nodule rupture was confirmed on ultrasound. The patient was placed on antibiotics and symptoms resolved.

The second case was a 67 year‐old male with a large left thyroid nodule causing tracheal deviation. Ultrasound showed the nodule measuring 3.9x5.8x7.7 cm and FNA was negative. RFA was performed and sixty‐six days later, the patient developed sudden neck pain with erythema and bloody, serous drainage from the RFA site. Nodule rupture was confirmed on ultrasound and he was treated with antibiotics, with resolution of his symptoms.

Nodule ruptures after RFA are a rare major complication. Although studies have shown that larger nodules and longer procedural times are associated with nodule rupture, and likely the need for invasive management after rupture, there may be an association between electrode size and nodule rupture. Both cases discussed occurred after using a 17 gauge electrode, one of the larger electrodes available, and both cases were managed conservatively. Larger electrode size may account for some delayed hemorrhage seen in ruptures. More studies are necessary to evaluate electrode size and nodule rupture.

POSTER 388

Thyroid Nodules and Goiter Case Study Poster

THYROSEQ^® TESTING FOR A BETHESDA III NODULE IDENTIFIES AN ACTIVATING TSHR MUTATION

Mohammad Islam*¹, Alexandra Dumitrescu², Roy Weiss¹

¹University of Miami Miller School of Medicine, Department of Medicine, USA,²University of Chicago, Department of Medicine, USA

IINTRODUCTION: Early detection of autonomous functioning thyroid nodules can be challenging when the patient is asymptomatic and TSH values are normal. Although the nodules may be non‐cancerous, identification of a clonal mutation at a high level may indicate neoplasia and the propensity for progression.

CASE DESCRIPTION: A 59 yo male of Sephardic descent, with history of obesity treated with semaglutide, was referred for a multinodular goiter incidentally found on a chest CT performed for evaluation of dyspnea. Thyroid ultrasound demonstrated a dominant right middle lobe nodule 27x18x33 mm TI‐RADS 3 and a dominant lower left lobe nodule 12x10x23 TI‐RADS 4 as well as 2 smaller nodules on the left and right lobes. Physical exam was remarkable for a 30 gram multinodular goiter. Pulse of 75 beats/min, BMI was 28.25 and he appeared euthyroid.

RESULTS: Review of thyroid function tests over the last 5 years revealed gradual but not complete suppression of the TSH from 0.53 to 0.29 (normal range 0.27‐4.20 mU/L), with mid normal range FT4 and FT3 and negative thyroid stimulating immunoglobulin and thyroperoxidase antibodies. Fine needle aspiration of the dominant nodules revealed one to be Bethesda II and the other was classified as Bethesda III, atypia of undetermined significance, which prompted reflex Thyroseq^® testing. No mutations or gene fusions associated with high probability of thyroid cancer were identified. However, an isolated TSH receptor TSHR mutation (p.I486M, c.1485C>G) was identified, with an allele frequency of 36% indicating a somatic mutation with high clonality. This TSHR mutation located in the first extracellular loop was previously reported in a toxic adenoma and was shown to have strong activation of the cAMP pathway in transfected COS‐7 cells1.

DISCUSSION: Histological evaluation of autonomous thyroid nodules is known to show a wide spectrum of abnormalities. In this asymptomatic patient with progressive decreasing TSH, routine TSHR sequencing as part of the Thyroseq^® testing for a Bethesda III nodule revealed an incidental finding of an activating mutation. This result enables consideration for early treatment, before development of clinical hyperthyroidism and thus potentially preventing clonal progression of this autonomous nodule.

POSTER 389

Thyroid Nodules and Goiter Clinical Poster

COST‐EFFECTIVENESS OF THYROID LOBECTOMY VERSUS TOTAL THYROIDECTOMY FOR NON‐BENIGN THYROID NODULES WITH LOW‐RISK PREOPERATIVE FEATURES

Vaninder Dhillon*¹, Jenna Mammen², Megan Tschudy²

¹Johns Hopkins University, USA,²Johns Hopkins University, USA

Objective: To demonstrate that thyroid lobectomy is cost‐effective in treatment of non‐benign thyroid nodules with low‐risk preoperative features, with less risk for post‐operative complication costs. Methods: Cost‐effective analysis. Results: Thyroid lobectomy is cost‐effective over total thyroidectomy for thyroid nodules with low‐risk preoperative features within the Bethesda III‐V category. There is a significant cost‐effectiveness in lobectomy over total thyroidectomy when considering post‐operative complication profiles, as well as improved quality of life. Discussion/conclusion: Thyroid lobectomy is cost effective in the treatment for non‐benign thyroid nodules with low‐risk preoperative features, and further studies should evaluate risk benefit profile.

POSTER 390

Thyroid Nodules and Goiter Clinical Poster

SINGLE AND COMBINED ASSOCIATIONS OF SERUM METAL WITH THYROID NODULES: A CROSS‐SECTIONAL STUDY

Qintao Ma¹, Ying Li¹, Genfeng Yu¹, Siyang Liu¹, Yuqi Jiang¹, Hualin Duan¹, Dongmei Wang¹, Yajun He¹, Nanfang Yao¹, Heng Wan², Jie Shen*²

¹Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), China,²Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), China

Objective: There is a scarcity of studies on the single and combined interactions between the serum metal elements and thyroid nodules. This current research aims to investigate the association between the serum metal elements (magnesium, iron, copper, zinc, and calcium) with thyroid nodules considering metal elements individually and as joint exposure.

Methods: A total of 8613 Chinese community‐dwelling adults were included in our study. We collect basic information through questionnaires and medical checkups. Logistic regression and three novel machine learning algorithms (Quantile G‐computation (QGC) model, Bayesian kernel machine regression (BKMR) model, and weighted quantile sum (WQS) regression model) were used in our study.

Result: In the logistic regression, we found a positive association between calcium and copper concentrations and the prevalence of thyroid nodules (all P < 0.05). Furthermore, we found a significantly positive correlation between the mixture of serum metal elements and the prevalence of thyroid nodules with the help of BKMR, WQS, and QGC model (all P < 0.05) in the total population. In further gender stratified analysis, we found that this association was statistically significant in the female group by QGC while not in males.

conclusion: The imbalance of selected metal elements may play a more important role in the association of serum metal elements with thyroid nodules. It is plausible that over‐supplementation with total metal elements may be associated with an elevated risk of thyroid nodules, especially for women. Our findings reveal the role of serum metal elements in the development of thyroid nodules and future prospective studies are needed to further confirm the single and combined associations

ORAL 25

Thyroid Imaging Clinical Oral

AI‐THYROID: PILOT RESULTS FOR EVALUATING THYROID MALIGNANCY IN CHILDREN

Eun Ju Ha*^1,2, Jeong Hoon Lee², Natalie Mak¹, Allison Duh¹, Elizabeth Tong¹, Kristen Yeom¹, Kara Meister³

¹Department of Radiology, Lucile Packard Children's Hospital, Stanford University, USA,²Department of Radiology, Ajou University School of Medicine, Korea, Republic of,³Department of Otolaryngology‐Head & Neck Surgery, Lucile Packard Children's Hospital, Stanford University, USA

Objective: Although less common in children compared to adults, thyroid cancer represents the most common pediatric endocrine malignancy. Prior studies have shown feasibility of AI models for predicting malignant thyroid nodules in the adult population. Studies on AI model performance and validation on the pediatric population are presently lacking. Here, we examine applicability of AI in the evaluation of thyroid nodules in children.

Methods: Pediatric cohorts (N = 123; mean age,15.4 ± 2.4 years; 99 female) who obtained ultrasound for thyroid nodule(s) and had histological confirmation were retrospectively identified from two independent institutions (Ajou University Medical Center, South Korea; Stanford Lucile Packard Children's Hospital, USA). AI‐Thyroid, a deep learning model for identifying malignant thyroid nodules and learned on adult population ¹, was tested on the pediatric cohorts on the following scenarios: (a) scenario 1: nodules, with axial US images; (b) scenario 2, nodules, with longitudinal US images; and (c) scenario 3, nodules, with both axial and longitudinal US images together. Model performance was compared against blinded expert radiologist performance using TIRADSs interpretation (ACR‐, ATA‐, and K‐TIRADS).

Results: A total of 150 thyroid nodules were analyzed, 44 (29.3%) comprising malignant nodules. Based on the radiologists' TIRADSs interpretation, the sensitivity and specificity were 86.4‐93.2% and 45.3‐78.3%, respectively. Using AI‐Thyroid, the AUROC, sensitivity, and specificity were: (a) scenario 1: 0.894, 72.7%, and 86.7%; (b) scenario 2: 0.927, 77.3%, and 89.5%; (c) scenario 3: 0.904, 86.4%, and 79.1%. The AUROC did not differ significantly between the pediatric cohorts from the two institutions (p = 0.410).

Conclusion: We present high performance of AI‐Thyroid on the pediatric population. Future investigations could include additional approaches to optimizing AI‐Thyroid tailored to pediatric population, such as transfer learning from adult population, fine‐tuning on pediatric cohorts, and, image synthesis, as well as implications of AI as an adjunct tool alongside tissue sampling in the ENT clinics.

ORAL 26

Thyroid Imaging Translational Oral

NOVEL INTEGRATION OF TOPOLOGICAL DATA ANALYSIS INTO A MULTIMODAL MACHINE LEARNING MODEL TO PREDICT FOLLICULAR CARCINOMA ON ULTRASOUND

Andrew Thomas*¹, Ann Lin², Yuchen Xu¹, Grace Deng¹, Gustavo Fernandez‐Ranvier², Aida Taye², Randall Owen², David Matteson¹, Denise Lee²

¹Cornell University, USA,²Icahn School of Medicine at Mount Sinai, USA

Objective: Multiple ultrasound (US) risk stratifications systems (RSS) have been developed to estimate malignancy risk in thyroid nodules and to recommend the need for fine needle aspiration biopsy. However, sonographic risk patterns identified in established RSSs may not accurately stratify follicular carcinoma from adenoma, which share many similar US characteristics. Quantitative medical imaging analysis aims to extract high‐dimensional textural features from tumor phenotypes that are imperceptible to the human eye. The purpose of this study is to investigate the performance of a multimodal machine learning model utilizing radiomics and topological data analysis (TDA) to predict malignancy in follicular thyroid neoplasms on ultrasonography.

Methods: This is a retrospective study of patients who underwent thyroidectomy with pathology confirmed follicular adenoma or carcinoma at a single academic medical center between 2010‐2022. The nodule of interest on pre‐operative ultrasound was annotated and masked to only include pixels. Images were scaled to maintain aspect ratio and ensure similar image resolution. Features derived from radiomics and TDA were calculated. High‐dimensional radiomics and TDA features were projected onto their first two principal components respectively. Logistic regression with an L2 penalty was used to predict malignancy. Classifier performance was evaluated using leave‐one‐out cross‐validation and area under the curve (AUC).

Results: Patients with follicular adenomas (n = 7) and follicular carcinomas (n = 11) with available imaging were included. 910 radiomics features were extracted for each image. 180 topological features from the height filtration, mean and variance of pixel intensities, the aspect ratio of images and two additional persistence statistics were derived from each image. The models achieved an AUC of 0.67 (radiomics only) and 0.87 (radiomics and TDA). Bootstrapping was used to assess the confidence of these statistics.

Discussion: We demonstrate that inclusion of topological features can yield strong improvement over the use of radiomics‐based features alone in the prediction of follicular carcinoma on ultrasound. Despite low volume data, the TDA features of height filtration with its connection to persistent homology transform (PHT) explicitly capture shape information that likely augments performance of the multimodal machine learning model. This approach suggests that a quantitative based US RSS may contribute to the preoperative prediction of follicular carcinoma.

ORAL 27

Disorders of Thyroid Function Clinical Oral

PERFORMANCE VALIDATION OF A MACHINE LEARNING‐ASSISTED SYSTEM FOR PREDICTING CLINICAL ACTIVITY SCORE IN THYROID‐ASSOCIATED ORBITOPATHY AND COMPARISON WITH OPHTHALMOLOGISTS

Kyubo Shin*¹, Jae Hoon Moon^1,2,3, Gyeong Min Lee⁴, Seongmi Kim⁵, Jae Hyuk Kim⁶, Richul Oh⁶, Jisun Park⁶, Sang Muk Lee⁷, Jaemin Park¹, Min Joung Lee⁷, Hokyung Choung⁸, Namju Kim⁵

¹THYROSCOPE INC., Korea, Republic of,²Department of Internal Medicine, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Korea, Republic of,³Center for Artificial Intelligence in Healthcare, Seoul National University Bundang Hospital, Korea, Republic of,⁴Department of Ophthalmology, Dongguk University Ilsan Medical Center, Korea, Republic of,⁵Department of Ophthalmology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Korea, Republic of,⁶Department of Ophthalmology, Seoul National University Hospital and Seoul National University College of Medicine, Korea, Republic of,⁷Department of Ophthalmology, Hallym University Sacred Heart Hospital and Hallym University College of Medicine, Korea, Republic of,⁸Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center and Seoul National University College of Medicine, Korea, Republic of

Background: A machine learning (ML)‐assisted system to mimic highly experienced ophthalmologists' clinical activity score (CAS) assessment using digital facial images for diagnosing active thyroid associated orbitopathy (TAO) was developed. In this study, we validated the performance of this ML‐assisted system and compared with ophthalmologists with various clinical experience.

Methods: We previously developed an ML‐assisted system designed to assess five CAS components (redness of the eyelids, redness of the conjunctiva, swelling of the eyelids, inflammation of the caruncle and/or plica, and conjunctival edema) in patients' facial images and to predict active TAO by considering two components of subjective symptoms (spontaneous retrobulbar pain and pain on gaze). This system divided 298 facial images from TAO patients with various activity to active (CAS ≥3) or inactive (CAS <2) TAO. Three ophthalmology residents, 3 general ophthalmologists with less than 5 years of clinical experience, and 3 TAO specialists with over 15 years of experience independently interpreted the same set of images and compared their results with those generated by the ML‐assisted system.

Results: The ML‐assisted system showed a sensitivity of 79.47%, specificity of 84.26%, and an f1 score of 0.7029 for diagnosing active TAO. On the other hand, the average sensitivity, specificity, and f1 score values for ophthalmology residents were 81.78%, 47.38%, and 0.5033, respectively. The values for general ophthalmologists were 88.00%, 68.31%, and 0.6292, respectively. The values for TAO specialists were 77.33%, 87.89%, and 0.7334, respectively.

Conclusion: Our ML‐assisted system has demonstrated a reasonable level of accuracy in detecting inflammatory active TAO. While this system may not replace the expertise of TAO specialists, it has shown a similar level of accuracy in diagnosing active TAO and outperforms that of ophthalmology residents and general ophthalmologists. Implementing this ML‐assisted system can provide a reliable and consistent assessment of disease activity, enabling early diagnosis and timely treatment of active TAO.

ORAL 28

Thyroid Nodules and Goiter Clinical Oral

EVALUATING CHATGPT QUERIES ON THYROID NODULES FOR PATIENT EDUCATION

Daniel Campbell*, Eric Mastrolonardo, Elliott Sina, Elizabeth Cottrill

Thomas Jefferson University Hospitals, USA

Objective: Patients are rapidly increasing usage of online resources, with data suggesting about 80% of Internet users seek health information online. ChatGPT is a large language model that understands and generates human‐like text in a conversation‐based fashion. It is the fastest‐growing application in history, reaching over 100 million users within four months of release. Given the prevalence of thyroid nodules, our study seeks to evaluate the quality of ChatGPT responses to questions about thyroid nodules for patient education.

Methods: ChatGPT was queried four times with an identical set of 30 questions pertaining to thyroid nodules. Each query differed based on the situation that the chatbot was initially “prompted” to converse: no prompting (Form 1), patient‐friendly responses (Form 2), physician‐level responses (Form 3), or prompting for references (Form 4). Questions were grouped into four categories: epidemiology, diagnosis, prognosis, and management. Answers were scored on a hierarchical scale: incorrect, partially correct, correct, or correct with referenced citation. For each answer, a Flesch‐Kinkaid (FK) grade level was calculated and referenced citations were analyzed for legitimacy and correctness. Proportions of responses at incremental score thresholds were compared by prompt type using chi‐squared analysis. The relationship between prompt type and grade level was assessed using ANOVA.

Results: Across all prompts, 83 answers (69.2%) were at least correct. Proportions of responses that were at least correct did not differ by prompt type (Chi‐squared, p = 0.402). Form 3 responses had a significantly lower grade level (13.43 ± 2.86) than Form 1 (14.97 ± 2.01), Form 2 (14.05 ± 2.77), and Form 4 (16.43 ± 2.047) (ANOVA, p < 0.0001). Form 4 provided 80/83 (96.4%) of all ChatGPT provided references. Of the provided references that were legitimate citations (73/83, 88.0%), 61 (83.6%) provided accurately cited information.

Discussion/Conclusion: ChatGPT overall provides appropriate answers to most questions on thyroid nodules regardless of prompting. While prompting decreases response grade level, all responses remained above accepted recommendations for presenting medical information. Given its rapid utilization and future potential, ChatGPT should be further scrutinized by thyroid specialists to better characterize information their patients may be consuming.

ORAL 29

Thyroid Nodules and Goiter Clinical Oral

LONG‐TERM CLINICAL OUTCOMES AFTER RADIOACTIVE IODINE TREATMENT FOR AN AUTONOMOUS FUNCTIONAL THYROID NODULE

Ai Yoshihara*, Jaeduk Noh, Hideyuki Imai, Shigenori Hiruma, Masako Matsumoto, Nami Suzuki, Miho Fukushita, Natsuko Watanabe, Kiminori Sugino, Koichi Ito

Ito Hospital, Japan

Objective: There have been few reports on the therapeutic effects of 131I treatment (RAIT) on thyroid function and tumor volume reduction in large series of cases of autonomously functioning thyroid nodule (AFTN).

Methods: We extracted the records of 247 patients diagnosed with AFTN between March 2005 and December 2020 who underwent RAIT at a dose of 13.5 mCi. All nodules were confirmed to be benign based on a cytology test. Of the 201 patients who were followed up for more than 2 years, 4 had undergone RAIT twice, and 3 had undergone RAIT 3 times. In addition, four of these 201 patients had undergone surgery after RAIT. We investigated the efficacy of RAIT in normalizing the thyroid hormone levels and reducing the volume of functioning nodules of the 190 of these long‐term follow‐up patients who had undergone RAI treatment only once and had not undergone surgery.

Result: At the time of diagnosis, the median age of the 190 patients was 52 years old, and they had an initial FT3 level of 5.2 pg/ml (range: 3.0‐22.4) and initial FT4 level of 1.69 ng/dl (0.93‐7.01). Before RAIT, their median tumor volume was 10.7 ml (range: 0.7‐113.6). The median follow‐up period after RAIT was 1433 days. As of each patient's most recent hospital visit, thyroid function was normal in 142 patients (74.7%), 45 patients (23.7%) had hypothyroidism, and hyperthyroidism persisted in 3 patients (1.6%). The median time to normalization of thyroid hormone levels was 90 days, and the median time to hypofunction was 178 days. Thyroid tumors increased after a single RAI treatment in 18 (9.0%) of the 201 patients who underwent more than one RAIT and the patients who underwent surgery. Nodule volume had decreased to 47.0% of the pre‐treatment volume at 1 year, to 36.9% at 2 years, and to 29.8% at 3 years.

Conclusion: RAIT for AFTN provided an overall of thyrotoxicosis cure rate of 98.4% of all 190 patients. During the long‐term follow‐up period, a reduction in nodule volume was observed in most of the patients, but 9% experienced tumor growth.

ORAL 30

Thyroid Nodules and Goiter Clinical Oral

UNNECESSARY THYROID SURGERY RATE IN THE ABSENCE OF MOLECULAR TESTING

Maria Mavromati*, Essia Saiji, Marco Stefano Demarchi, Vincent Lenoir, Paulina Kuczma, Francois Jornayvaz, Claudio De Vito, Minerva Becker, Frederic Triponez, Sophie Leboulleux

Geneva University Hospital, Switzerland

Background: Molecular testing for Bethesda III, IV and V thyroid nodules is widely available in the US, but still not used in Europe due to reimbursement issues.

The aim of this study was to assess the rate of unnecessary surgery performed in a real life setting for Bethesda III, IV and V nodules in the absence of molecular testing and to assess the rate of surgeries that could have been spared with the use of these tests.

Method: This is a single‐center retrospective study of consecutive patients undergoing FNAB with cytologic analysis with rapid on‐site evaluation between January 2017 and December 2021.

Unnecessary surgery was defined as surgery performed because of Bethesda III, IV or V results in the absence of local compressive symptoms with final benign histology and as second surgery for completion thyroidectomy due to malignancy on initial lobectomy.

Results: Among 862 patients (640 women, mean age 54.2 years), 1010 nodules (median size 22.2 mm) underwent 1189 FNAB. Nodules were classified as EU‐TIRADS 2, 3, 4 and 5 in 3%, 34%, 42% and 22%, respectively. FNAB cytology was Bethesda I, II, III, IV, V and VI in 8%, 48%, 17%, 17%, 3% and 6%, respectively. Surgery was performed in 35.6% (62/174) of Bethesda III nodules (52 patients), in 73.8% (124/168) of Bethesda IV nodules (114 patients) and in 96.7% (29/30) of Bethesda V nodules (24 patients). Final histology was benign in 81%, 76% and 21% of Bethesda III, IV and V nodules, respectively. Surgery was considered useless in 56% (29/52), 69% (79/114) and 21% (5/24) of patients undergoing surgery for Bethesda III, IV and V nodules, respectively.

Conclusion: In this real data cohort, surgery was more frequently performed in Bethesda IV and V nodules compared to Bethesda III nodules. Surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

ORAL 31

Thyroid Cancer Clinical Oral

MOLECULAR TESTING FOR BETHESDA III THYROID NODULES: TRENDS IN IMPLEMENTATION, CYTOPATHOLOGY CALL RATES, SURGERY RATES, AND MALIGNANCY YIELD AT A SINGLE INSTITUTION

Mason Stillman*¹, Eric Kuo¹, Rachel Liou¹, James Lee¹, Jennifer Kuo¹, Catherine McManus²

¹Columbia University Irving Medical Center, USA,²Columbia University Irving Medical Center, USA

Objective: Molecular testing (MT) has become standard practice as a way to more accurately rule out malignancy in indeterminate Bethesda III (BIII) thyroid lesions. We sought to assess the adoption of this technology across both community and academic sites, as well as the impact it has had on cytology reporting, malignancy yield, and rates of surgery.

Methods: We performed a retrospective cohort study including all fine needle aspirations (FNAs) analyzed at our institution from 2017‐2021, including samples sent from community institutions. We analyzed trends in MT utilization by platform and by community or academic site. We compared BIII call rates, MT utilization rates, rates of subsequent surgery, and malignancy yield on final pathology before and after MT became readily available using chi‐square analysis and linear regression.

Results: A total of 8,960 FNAs were analyzed at our institution from 2017‐2021. There was broad adoption of MT across both community and academic sites. There was a statistically significant increase in both the BIII call rate and the utilization of MT between the pre‐ and post‐MT periods (p < 0.001 and p < 0.001). There was no decrease in the rate of surgery per FNA (p = 0.521), and although the malignancy yield on final pathology decreased from 61.9% to 51.3%, it was not statistically significant (p = 0.173). Finally, PPV of MT decreased from 0.85 to 0.5 (p = 0.008).

Conclusion: The increased availability of molecular testing platforms may have led to an unintended increase in the rates of BIII lesions, the rates of molecular testing, and the rates of surgery for nodules that are truly benign. Physicians who utilize molecular testing need to be aware of the limitations of this technology in order to properly and appropriately counsel patients.

ORAL 32

Thyroid Nodules and Goiter Clinical Oral

FALSE‐NEGATIVE BIOPSY RATES ARE NOT INCREASED FOR THYROID NODULES >4 CM IF NON‐SURGICAL MANAGEMENT IS INCLUDED IN ANALYSIS

Melbin Thomas*, Allysha Yasuda, Tracy Tylee

University of Washington, USA

Introduction: Management of Bethesda‐II (B‐II) thyroid nodules ≥4 cm is controversial. While the false negative rate for thyroid fine needle aspiration biopsy (FNAB) is reported to be approximately 3%, several studies report rates as high as 35% for nodules >4 cm. This has led some to recommend benign thyroid nodules >4 cm undergo thyroidectomy to avoid missing a diagnosis of malignancy. However, these studies only included patients who underwent thyroid surgery, which represents a small subset of large benign nodules. This may overestimate the false negative FNAB risk for this group. Our study attempts to address this concern by following all nodules >4 cm with benign FNAB for up to 10 years to evaluate for malignancy based on surgery, repeat FNA or changes on US.

Methods: We conducted an IRB approved retrospective chart review identifying all patients who underwent FNAB at a single institution between 2008 – 2014 with nodules >4 cm and B‐II results. Nodules were considered benign if they had 1) benign pathology on surgical resection, 2) repeat FNAB with B‐II results or 3) no changes in imaging characteristics on US after 2+ years.

Results: 48 patients with nodules >4 cm had B‐II cytology and 2+ years follow up (average 5 years, range 2.2 ‐ 9.7 years). Of these, 23 underwent surgery, 9 had repeat FNA and 15 had US follow up. Surgery identified 2 malignancies (false negative rate of 8.7%). Of non‐surgical patients, all repeat FNABs were benign, and all but one repeat US showed no significant change. False negative FNAB rate including all patients was 4.4%.

Discussion: This study shows false negative FNAB results are not markedly elevated if all >4 cm nodules are evaluated, but rates were considerably higher if limited to surgical patients. Surgical patients may have higher risk features, which could explain the higher false negative FNAB results for this group. Further study is needed to determine if size alone is a risk factor for false negative FNAB in large B‐II nodules, and if clinical surveillance is appropriate treatment for these patients.

ORAL 33

Thyroid Cancer Clinical Oral

PATIENT REPORTED OUTCOMES: WHAT SYMPTOMS DO LONG TERM THYROID CANCER SURVIVORS EXPERIENCE?

Thomas Szabo Yamashita*, Khavya Avula, Jerica Podrat, Johnny Rollins, Soo‐Hyun Lee‐Kim, Yi‐Ju Chiang, Loretta Williams, Mark Zefereo, Paul Graham, Nancy Perrier, Mouhammed Habra, Elizabeth Grubbs, Sarah Fisher

MD Anderson, USA

Objective: Available literature examining quality of life (QOL) of patients with thyroid cancer suggest significant impairment in QOL similar to that of other cancer survivors. We sought to define QOL using The MD Anderson Symptom Inventory – Thyroid (MDASI‐Thy) in a population of long‐term thyroid cancer survivors.

Methods: Single institution retrospective review of patient reported outcomes (PRO) between 09/01/2019–12/31/2022. The MDASI‐Thy is prospectively administered at each visit for all adult patients followed in the Thyroid Cancer Survivorship clinic (TCSC). Patients with history of thyroid cancer are risk stratified (low/moderate/high) and enrolled in TCSC for ongoing surveillance at 1, 3, and 5 years after diagnosis, respectively, provided there is no radiographic or biochemical evidence of disease recurrence.

Results: A total of 1674 patients have been followed at the TCSC. The majority are female 77% (n = 1287) with a median age 61 years (range 25‐97). Papillary thyroid cancer is the most common diagnosis (66%, n = 1114). Most presented with Stage I disease at diagnosis (66%), 43% of patients had ≤T2 tumors, and 33% were N0/Nx. Median follow‐up was 36 months (range 0‐139 months). The median time from surgery was 11.8 years (range 1.3‐27.9). 2694 questionnaires were sent and 1623 (63%) were answered. Sixty‐two percent of patients reported fatigue (56% mild, 26% moderate, 33% severe), 32% sadness (73% mild, 18% moderate, 12% severe), 26% hoarseness (80% mild, 13% moderate, 9% severe), 25% dyspnea (76% mild, 16% moderate, 11% severe), 24% dysphagia (79% mild, 2% moderate, 11% severe), 17% reported pain (65% mild, 22% moderate, 20% severe). Although survivors frequently reported the presence of symptoms, only a minority were scored as severe, prompting electronic health record notifications to providers (11% of all patients for fatigue, 3% sadness, 2% pain, 2% dysphagia, 2% dyspnea, and 2% hoarseness).

Discussion/Conclusions: Thyroid cancer survivors commonly experience changes to their QOL after thyroidectomy, although the majority experience symptoms rated as mild or moderate. Improved understanding of the subpopulation of long‐term thyroid cancer survivors who are at highest risk for impaired QOL will aid in the development of guidelines for thyroid cancer survivorship care.

ORAL 34

Thyroid Cancer Clinical Oral

RURAL‐URBAN DISPARITIES IN THE CONTINUUM OF THYROID CANCER CARE: ANALYSIS OF 92,794 CASES

Hattie Huston‐Paterson*^1,2,3, Yifan Mao¹, Jiyoon Kim⁴, Chi‐Hong Tseng⁵, James Wu¹, Michael Yeh¹

¹Section of Endocrine Surgery, University of California Los Angeles, USA,²Veterans Health Administration, Greater Los Angeles Healthcare System, USA,³National Clinician Scholars Program, USA,⁴Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, USA,⁵Department of Medicine, University of California Los Angeles, USA

Objective: Rurality is associated with higher incidence and higher disease‐specific mortality for most cancers. Outcomes for rural and ultra‐rural (“frontier”) patients with thyroid cancer are poorly understood.

Methods: We queried linked California Cancer Registry and California Office of Statewide Health Planning and Development databases for patients diagnosed with thyroid cancer (1999‐2017). We analyzed the Medical Service Study Area category, disease stage at diagnosis, time from diagnosis to surgery, use of guideline‐concordant radioactive iodine (RAI) ablation, surveillance status, and overall and disease‐specific mortality. Cox and logistic regression models controlled for demographic (age, sex, socioeconomic status, insurance status, and race) and clinical covariates (stage at diagnosis, Charlson Comorbidity Index, treatment at a Commission on Cancer‐accredited facility, tumor size, extrathyroidal extension, lymphovascular invasion, and aggressive tumor variants) in a step‐wise manner.

Results: Our cohort comprised 92,794 subjects: (65,475 women [70.6%]; mean age 50.0 years). Compared to urban patients, rural and frontier patients were more likely to be White, uninsured, and from lower quintiles of socio‐economic status (p < 0.01). Distant disease at diagnosis was more common in rural (56.0 vs. 50.4 cases per 1,000 new cases) and frontier patients (80.9 vs. 50.4 per 1,000) compared to urban patients. The incidence of medullary thyroid cancer was greater in rural patients (17.9 vs 13.6 cases per 1,000) and frontier patients (31.0 vs 13.6 per 1,000) compared to urban patients. The incidence of anaplastic thyroid cancer was higher in frontier vs urban patients (15.5 vs 7.1 per 1,000).

Frontier patients were less likely to receive guideline‐concordant RAI ablation (OR 0.76; 95% confidence interval [CI] 0.61‐0.95). Rural and frontier patients were more often lost to follow‐up (OR 1.56; 95% CI 1.49‐1.63, and OR 2.38, 95% CI 1.88‐3.03, respectively) and had higher disease‐specific mortality (OR 1.18; 95% CI 1.07‐1.30, and OR 1.92; 95% CI 1.22‐2.77, respectively). Rural and frontier residence was independently associated with being lost to follow‐up.

Conclusion: Compared to their urban counterparts, rural and frontier patients with thyroid cancer present with later‐stage disease and experience higher disease‐specific mortality. They also are more often lost to follow‐up, which presents an opportunity for targeted outreach to reduce the observed disparities in outcomes.

ORAL 35

Thyroid Cancer Clinical Oral

PREDICTORS OF POOR EMOTIONAL QUALITY OF LIFE IN PATIENTS WITH DIFFERENTIATED THYROID CANCER – RESULTS OF A PROSPECTIVE INTERNATIONAL STUDY

Gerasimos Sykiotis*¹, Akram Al‐Ibraheem², Deborah Engesser³, Monica Pinto⁴, Ioannis Iakovou⁵, Arild Østhus⁶, Eva Hammerlid⁷, Laura Locati⁸, Eva Gamper⁹, Juan Ignacio Arraras¹⁰, Susan Jordan¹¹, Naomi Kiyota¹², Matthias Büttner³, Rita Canotilho¹³, Georgios Ioannidis¹⁴, Olga Husson¹⁵, Ricardo Gama¹⁶, Giuseppe Fanetti¹⁷, Laura Moss¹⁸, Johanna Inhestern¹⁹, Guy Andry²⁰, Dagmar Führer²¹, Harald Rimmele²², Susanne Singer³

¹Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, Switzerland,²Thyroid Cancer Service, King Hussein Cancer Centre, Jordan,³Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Centre Mainz and University Cancer Centre, Germany,⁴Rehabilitation Medicine Unit, Strategic Health Services Department, Istituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Italy,⁵Department of Nuclear Medicine, Aristotle University, Greece,⁶Department of Head, Neck, and Reconstructive surgery, Oslo University Hospital, Rikshospitalet,, Norway,⁷Department of Otolaryngology and Head and Neck Surgery, Sahlgrenska University Hospital, Sweden,⁸Head and Neck Medical Oncology Unit; Fondazione IRCCS istituto Nazionale dei Tumori, Italy,⁹Department of Nuclear Medicine and Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Austria,¹⁰Oncology Departments, Complejo Hospitalario de Navarra, Spain,¹¹School of Public Health, The University of Queensland, Australia,¹²Department of Medical Oncology and Hematology, Kobe University Hospital, Japan,¹³Instituto Português do Oncologia do Porto Francisco Gentil, Portugal,¹⁴Oncology Department, Nicosia General Hospital, Cyprus,¹⁵Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Netherlands,¹⁶Hospital de Cancer de Barretos, Brazil,¹⁷SOC Oncologia Radioterapica, IRCCS Centro di Riferimento Oncologico di Aviano, Italy,¹⁸Velindre Cancer Centre, Velindre University NHS Trust, United Kingdom,¹⁹Department of Otorhinolaryngology, Oberhavelkliniken, Germany,²⁰Surgery Department, Jules Bordet Institute, Belgium,²¹Department of Endocrinology, University Medical Centre Essen, Germany,²²Bundesverband Schilddrüsenkrebs ‐ Ohne Schilddrüse leben e.V., Germany

Objective: Quality of life (QoL) in patients and survivors with differentiated thyroid carcinoma (DTC) has been shown to be inferior to that of the general population. However, prospective predictors of poor QoL in general, and poor emotional functional in particular, have not been sufficiently elucidated. The aim of this study was to investigate variables that can predict poor emotional functioning in patients with DTC during the course of the disease and its treatment.

Methods: In a prospective cohort study, thyroid cancer patients from 15 countries completed the European Organisation for Research and Treatment of Cancer (EORTC) Core Questionnaire (C30) along with its Thyroid Cancer Module (THY34) before starting treatment (t1), 6 weeks later (t2), and again 6 months hereafter (t3). For the present analysis, data from patients with DTC were used. Poor emotional functioning at t3 was defined using the thresholds for clinical importance provided by Giesinger et al. (2020). The following variables (values ascertained at t2) were considered for the prediction analysis using multivariate logistic regression: gender, UICC stage (I/II vs. III/IV), problems with body image, worry about important others, lacking social support, exhaustion, and discomfort in the head and neck.

Results: Of a total 303 thyroid cancer patients enrolled, 253 (83%) had DTC, of whom 196 participated at both t2 and t3 (9 declined, 6 had died, and 42 could not be contacted again at t3). Of these 196 participants, 44% had poor emotional functioning (i.e., worse than the threshold for clinical importance). With increasing exhaustion at t2, the likelihood of poor emotional functioning at t3 increased (odds ratio [OR] 1.03 per score point, 95% confidence interval [CI] 1.0‐1.05, p = 0.001). Increasing problems with body image at t2 also increased the likelihood of poor emotional functioning at t3 (OR per score point 1.01, CI 1.00‐1.02, p = 0.02). There was no evidence of an independent effect of female gender (OR 1.3, CI 0.6‐2.8, p = 0.55), advanced UICC stage (OR 0.8, CI 0.3‐2.2, p = 0.70), or any of the other quality of life domains on the likelihood of later emotional problems.

Conclusion: In patients with DTC undergoing treatment, severe fatigue and problems with body image are risk factors for later poor emotional functioning.

ORAL 36

Health Disparities/Health Equity Clinical Oral

BARRIERS TO GETTING IN THE DOOR FOR THYROID CANCER CARE

Debbie Chen*, Mousumi Banerjee, Brittany Gay, Yi Chun Wang, Lesley Miranda, Christine Veenstra, Megan Haymart

University of Michigan, USA

Objective. Differential access to physicians contribute to existing disparities in thyroid cancer care, with racial/ethnic minority patients at greater risk for worse outcomes. Prior studies have identified significant barriers in access to appointments for primary care and liver cancer care. Little is known about access to thyroid cancer care, and how patients' spoken language impacts their ability to schedule a clinic appointment.

Methods. Between 12/2021‐2/2023, we conducted an audit study of 127 outpatient clinics located across 12 demographically diverse states in the United States. Using standardized scripts, trained research personnel assigned to the roles of English‐speaking, Spanish‐speaking, and Mandarin‐speaking patients called the telephone number for the clinic that treats thyroid cancer, which was provided by the hospital general information personnel in prior work. Primary outcome was whether the simulated patient caller was provided with a clinic appointment date or information on how to schedule a new patient appointment (binary variable: yes/no). We used chi‐square tests and logistic regression analysis to test for associations between the primary outcome and: language, region type, and hospital teaching status.

Results: Of the 323 total calls, 40.2% (N = 130) of calls resulted in simulated patient callers being provided with a clinic appointment date or information on how to schedule an appointment. Most common barriers to obtaining the requested information included: staff said “no” or hung up on the caller (22.8%, N = 44), the call was disconnected inadvertently or because the automated message required input but did not provide language‐concordant instructions (21.8%, N = 42), and the call eventually went to voicemail (21.8%, N = 42). Simulated non‐English‐speaking patient callers were less likely to be provided with a clinic appointment date or information on scheduling an appointment for thyroid cancer care (Mandarin: OR 0.21 [95% CI 0.11‐0.38]; Spanish: OR 0.37 [95% CI 0.22‐0.64] compared to English).

Conclusion. Our study highlights significant barriers that patients may encounter in trying to obtain thyroid cancer care due to obstacles in scheduling new patient clinic appointments, with non‐English‐speaking patients at greater risk for worse access. Interventions focused on mitigating systems‐level barriers are necessary to increase access to thyroid cancer care for all patients.

HIGHLIGHTED POSTER 100

Thyroid Cancer Translational Highlighted Poster

TARGETING AGGRESSIVE THYROID CANCERS WITH TSHR CART CELLS

Justyna Gleba*¹, Aylin Alasonyalilar demirer², Claudia Manriquez‐Roman³, Matthew Pawlush², Elizabeth Siegler⁴, Ahmet Bilgili⁵, Reona Sakemura⁶, Michelle Cox⁶, Ismail Can⁶, Ekene Ogbodo⁶, Gaofeng Cui⁴, George Mer⁴, gLORIA Olivier⁴, Yushi Qiu¹, Robert Smallridge¹, Abba Zubair¹, Han Tun¹, Saad Kenderian⁷, John Copland²

¹Mayo clini, USA,²Mayo clinic, USA,³Mayo clinic, USA,⁴Mayo clini, USA,⁵Mayo Clinic, USA,⁶Mayo Clinic, USA,⁷Mayo clinic, USA

Objective: A majority of thyroid cancer deaths are attributed to a subset of poorly differentiated, metastatic tumors.

Methods: To combat this, we developed a potent anticancer strategy for the treatment of these aggressive thyroid tumors by combining the tumor sensitizing effects of mitogen‐activated protein kinase (MAPK) inhibitors and a novel thyroid hormone stimulating receptor (TSHR)‐ targeted (chimeric antigen receptor) CAR T cell therapy.

Results: TSHR‐stimulated CARTs proliferated, released type 1 cytokines, and killed cancer cells when co‐cultured with TSHR expressing cell lines both in vitro and in vivo. In addition, pretreatment of anaplastic patient‐derived tumor xenografts with MAPK/BRAF inhibitors led to enhanced TSHR expression and significantly longer survival than CART therapy or MAPK/BRAF inhibitors as single agents.

Discussion/Conclusion: Taken together, these studies may provide an effective strategy for treating radioiodide resistant TSHR positive and negative TSHR reversible thyroid tumors in cancer patients with the worst prognoses.

HIGHLIGHTED POSTER 101

Thyroid Cancer Translational Highlighted Poster

PLASMA‐BASED GENOTYPING FOR MONITORING PATIENTS WITH THYROID CANCER

Debora Thomaz*¹, Welbert Rocha¹, Renata Silva¹, Aline Viana², Rosa Biscolla³, Otavio Curione², Ana Panizza², João Martins³, Janete Cerutti¹

¹Universidade Ferderal de São Paulo, Brazil,²Hospital Heliópolis, Brazil,³Hospitak São Paulo, Brazil

Objective: We evaluated the feasibility of using plasma cell‐free DNA (cfDNA) and RNA (cfRNA) to detect the 10 most common thyroid cancer driver genes as a minimally invasive and complementary tool for monitoring patients diagnosed with thyroid cancer.

Methods: A retrospectives cohort (n = 320) of patients diagnosed with thyroid malignant neoplasm who underwent thyroidectomy, and the primary tumor was genotyped for 10‐gene panel, were matched with a prospective cohort (n = 60) for clinical follow up and genotyping. The prospective cohort included patients with persistent/recurrent disease and with no evidence of disease whose blood was collected for serum testing as part of routine clinical management. Their cfDNA and cfRNA was isolated and genotyped for the genetic variant previously detected in the primary tissue using nanoplate‐based digital PCR system (dPCR). The 10‐gene panel included BRAF V600E, RAS and TERT promoter pathogenic variants, and RET::PTC1‐3, PAX8::PPARG, STRN::ALK and AGK::BRAF fusions. The allele fractions of genetic variant detected in plasma was associated disease status.

Results: Using dPCR system we detected circulating tumor (ct) DNA and/or RNA in the plasma of patients classified with incomplete biochemical and/or structural response. Remarkably, in patients with distant metastasis, we observed concordance between mutations in the primary tumor and those detected in the plasm. Patients with indeterminate response to the treatment were either positive or negative for the mutations identified in the primary tumor, while no ctDNA or ctRNA was detected in patients with no evidence of disease.

Discussion/Conclusion: Although the methodology is still evolving, our findings suggest that this non‐invasive approach can be incorporated into the routine management of patients with malignant thyroid neoplasm as it may help the early detection of therapeutically targetable mutations. We emphasize that liquid biopsy test can be repeated through the follow‐up to complement existing tests with low cost and convenience for the patient. We also anticipate that that this blood test may help early detection of thyroid tumors.

HIGHLIGHTED POSTER 102

Thyroid Cancer Clinical Highlighted Poster

INITIAL ABLATION RATIO PREDICTING THE RECURRENCE OF LOW‐RISK PAPILLARY THYROID MICROCARCINOMAS TREATED WITH MICROWAVE ABLATION: A 5‐YEAR, SINGLE‐INSTITUTION COHORT STUDY

Shuhang Xu*¹, Yujie Ren², Chao Liu²

¹Nanjing University of Chinese Medicine, China,²Nanjing University of Chinese Medicine, China

Objective: To assess the long‐term efficacy and safety of microwave ablation (MWA) in treating low‐risk papillary thyroid microcarcinomas (PTMC), and to identify predictive factors for the postoperative local tumor progression of PTMC.

Methods: A total of 154 low‐risk PTMC patients treated with MWA who were followed up for a minimum of 3 months were retrospectively recruited. Ultrasonography was performed after MWA to assess the local tumor progression. Adverse events associated with MWA were recorded. The ablated volume (Va) and initial ablation ratio (IAR) were measured to assess their influences on the recurrence risk of PTMC.

Results: The mean tumor volume of PTMC before MWA was 0.071 (0.039, 0.121) cm, with a maximum diameter of 0.60 ± 0.18 cm. All PTMC patients were followed up for 6 (3, 18) months. Va increased immediately after MWA, then gradually decreased over time, till significantly smaller at 12 months than that before MWA (P < 0.05). The median volume reduction ratio (VRR) at 24 months reached 100%, which was maintained during a 60‐month follow‐up. A total of 7 (4.55%) cases of local tumor progression were recorded during the follow‐up. Kaplan‐Meier survival analysis revealed that the rate of local tumor progression was significantly lower in PTMC patients with a maximum tumor diameter <0.70cm than in those with ≥0.70cm (P = 0.031). A significant better prognosis was achieved in PTMC patients with IAR ≥15 than in those with IAR <15 (P = 0.015). Sex, age (<55 years) and preoperative thyroid‐stimulating hormone (TSH >2.0 mU/L) of PTMC patients were not correlated with local tumor progression.

Conclusion: MWA is an effective therapeutic strategy for low‐risk PTMC with a high safety. The maximum tumor diameter and IAR are predictive factors for the local tumor progression of PTCM after MWA.

HIGHLIGHTED POSTER 103

Surgery Clinical Highlighted Poster

REOPERATION RATES AFTER INITIAL THYROID LOBECTOMY FOR PATIENTS WITH THYROID CANCER: A NATIONAL COHORT STUDY

Marin Kheng*¹, Alexander Manzella¹, Joshua Chao¹, Amanda Laird^1,2, Toni Beninato^1,2

¹Rutgers Robert Wood Johnson Medical School, USA,²Rutgers Cancer Institute of New Jersey, USA

Objective: The 2015 ATA guidelines recommend thyroid lobectomy (TL) as an alternative to total thyroidectomy (TT) for the surgical treatment of low‐risk differentiated thyroid cancer. Multiple studies have since reported rising rates of TL despite concerns for an increased risk of disease recurrence and need for reoperation. The aim of this study was to examine changes in reoperation rates among patients who underwent TL and TT for malignancy.

Methods: We queried the Vizient Clinical Data Base to identify TL and TT performed pre‐guideline change (pre‐GC = 2013‐2015) and post‐guideline change (post‐GC = 2016‐2021). Reoperations included reoperative thyroid surgery (RTS) and neck dissection (ND). Timing of reoperation was defined as early (<180 days), thought to indicate inadequacy of initial operative choice, or late (180+ days), suggesting disease recurrence. Cox regression was used to evaluate factors associated with late reoperation.

Results: Of 65,627 patients, 20,895 (31.8%) underwent initial TL and 44,732 (68.2%) underwent initial TT; TL rose from 21.4% of total cases pre‐GC to 37.0% post‐GC (p > 0.001). In patients undergoing TL, the early RTS rate declined from 33.7% of cases pre‐GC to 13.9% post‐GC and the ND rate declined from 0.8%‐0.4% (p < 0.001). In patients undergoing TT, the early RTS rate remained 0.2%, while ND increased from 0.4%‐0.7% (p < 0.001).

The late RTS rate following initial TL also declined, from 2.0% pre‐GC to 1.7% post‐GC, while ND increased from 0.6%‐0.8% (p = 0.17). In TT patients, both late RTS and ND reoperation rates increased, from 0.2%‐0.3% (p = 0.04) and 1.7%‐2.1% (p < 0.01), respectively. The overall late reoperation rate for TL was 0.6% higher than the TT rate pre‐GC (p = 0.01) and 0.2% higher post‐GC (p = 0.18).

Undergoing initial operation at a high‐volume center (>100 cases/year) and reoperation for ND were associated with a decreased risk of late reoperation (HR = 0.87 [0.77‐0.99] and HR = 0.85 [0.74‐0.98], respectively). Uninsured status and more recent initial operation were associated with an increased risk of late reoperation (HR = 1.66 [1.06‐2.59] and HR = 1.22 [1.18‐1.28], respectively). The type of index operation performed and its timing in relation to the guideline change were not significantly associated with late reoperation.

Discussion/Conclusion: The rate of early reoperations declined for TL following the 2015 ATA guideline release, but late reoperations remained unchanged despite a significant shift in practice patterns towards performing initial TL. Since the guideline release, patients appear to be receiving less aggressive, guideline‐concordant care without a significant increase in the late reoperation rate for TL compared to TT.

HIGHLIGHTED POSTER 104

Thyroid Cancer Clinical Highlighted Poster

FEW PATIENTS WITH MEDULLARY THYROID CANCER UNDERGO GENETIC TESTING OR COUNSELING

Jennine Weller*¹, Tatiana Fedorova¹, Philip Crepeau¹, Colleen Kiernan², Elizabeth Grubbs³, Aarti Mathur¹, Lilah Morris‐Wiseman¹

¹Johns Hopkins University School of Medicine, USA,²Vanderbilt University School of Medicine, USA,³University of Texas MD Anderson Cancer Center, USA

Objective: Rearranged during transfection (RET) proto‐oncogene germline mutations cause an autosomal dominant hereditary cancer syndrome with medullary thyroid cancer (MTC). Because 25% of MTC cases are hereditary, genetic testing is essential for all patients with MTC to prevent or identify early cancer in the proband and first‐degree relatives. However, the frequency of genetic testing remains unknown. In patients with MTC, we aimed to identify the incidence of, and patient characteristics associated with genetic testing in a national retrospective cohort.

Methods: Using the TriNetX Diamond Network, a de‐identified database of electronic medical records for approximately 213 million patients in the US, we defined our MTC population as patients with thyroid cancer by ICD‐10 code (C73) who had 1) undergone at least total thyroidectomy and 2) had at least two measurements of calcitonin and carcinoembryonic antigen. The primary outcome was undergoing genetic counseling and/or testing. Chi‐squared and t‐tests examined associations between genetic workup and baseline demographics, comorbidities, and perioperative patient characteristics.

Results: Of the 460 patients with MTC, 171 (37.2%) patients underwent genetic workup; of those, 142 (83.0%) patients underwent genetic testing alone, 18 (10.5%) genetic counseling alone, and 11 (6.4%) both counseling and testing. MTC patients were female (62.2%), with a median age of 64 years (range 9 to ≥90). Genetic workup occurred in 33.3% of patients aged ≤30 years, 42.1% patients 31‐65 years, and 32.6% patients >65 years. On average, patients who underwent genetic workup were younger than those who did not (mean age difference 4.1 years, p = 0.011). There was no association between concomitant diagnosis of hyperparathyroidism or pheochromocytoma and genetic workup (p = 0.866 and 0.716, respectively). There were also no significant differences between surgical procedure (including lymph node dissection) and genetic testing patterns or between patient characteristics and genetic counseling vs. testing.

Discussion/Conclusion: Across all age groups, genetic testing occurred in less than half of surgical patients with MTC despite clear guidelines that all should undergo genetic testing. Few patients underwent genetic counseling. Future initiatives should focus on identifying barriers to and improving frequency of genetic testing and counseling in this population.

HIGHLIGHTED POSTER 105

Thyroid Cancer Clinical Highlighted Poster

LONGITUDINAL THYROID ULTRASOUND SCREENING IN PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS: SURVEILLANCE RECOMMENDATIONS

Ludovico Sehnem*¹, Gustavo Romero‐Velez¹, Salem Noureldine², Panagiotis Bletsis¹, Megan Parmer¹, Allan Siperstein¹

¹Cleveland Clinic, USA,²George Washington school of Medicine, USA

Objective: Patients with familial adenomatous polyposis (FAP) have increased risk of thyroid nodular disease. We have previously demonstrated that screening thyroid ultrasound (US) initially detects nodules in 38% and cancer in 2.6% of the patients. The purpose of this study is to define the value of serial US evaluation at identifying disease progression in patients with FAP.

Methods: Retrospective review from 2008 to 2023 at a single referral center. All patients with FAP and at least one screening US were included. Patient demographics, baseline US characteristics, follow‐up in regards to the development of new nodules and cancer were assessed. Time to event for outcomes were evaluated using Kaplan‐Meier analysis.

Results: A total of 556 patients underwent screening. 51% were male. Median age at first screening was 38 years old (range 8‐78). 81% underwent longitudinal follow‐up for a median length of 7 years. At initial screening, 30% had nodules, 10% underwent biopsy and 1.4% had cancer. For patients with normal baseline US, 8% developed a nodule by 5‐years and 15% by 10‐years. At 5‐years, cancer developed in 3% of the cohort with non‐biopsied or benign nodules at baseline screening versus 1% in patients with normal baseline US. At 10‐years, these numbers were 8% and 3%, respectively. The cumulative incidence of initial and subsequent cancer was 4% by 5‐years and 6% by 10‐years. Of the patients diagnosed with cancer, 30% were male with median age of 35 (range 17‐58). 80% were T1 based on American Joint Committee on Cancer (AJCC), 60% were multifocal and 40% were cribriform‐morular variant.

Conclusion: To our knowledge, this is the largest longitudinal study evaluating the development of thyroid cancer in patients with FAP. For patients who were diagnosed with cancer, 40% had it detected on initial screening and 60% on median longitudinal follow‐up of 7 years. Based on the Kaplan‐Meier analysis, ongoing longitudinal screening is warranted for patients with FAP. We would recommend patients found to have non‐biopsied or benign nodules be followed every 2 years and those with normal US can be safely followed every 5 years.

HIGHLIGHTED POSTER 106

Thyroid Cancer Clinical Highlighted Poster

PSYCHOMETRIC EVALUATION OF A NEW INSTRUMENT TO ASSESS THE SYMPTOMS FOLLOWING RADIOACTIVE IODINE THERAPY AMONG PATIENTS WITH DIFFERENTIATED THYROID CANCER: SALIVARY, LACRIMAL, NASAL (SALANS) QUESTIONNAIRE

Alaina Carr*¹, Jacqueline Jonklaas¹, Roxanne Jensen², George Luta¹, Chenlu Yu¹, Gary Bloom³, Bruce Davidson⁴, Giuseppe Esposito⁵, Samantha Diamond‐Rossi^6,7, Kristi Graves¹

¹Georgetown University, USA,²National Cancer Institute, USA,³ThyCa: Thyroid Cancer Survivors' Association, Inc., USA,⁴MedStar Georgetown University Hospital, USA,⁵Medstar Georgetown University Hospital, USA,⁶INOVA Schar Cancer Institute, USA,⁷INOVA Fairfax Hospital, USA

Objective: To psychometrically evaluate the reliability and validity of the SAlivary, LAcrimal, NaSal (SALANS) questionnaire.

Methods: We developed a novel questionnaire to assess symptoms related to salivary gland, lacrimal, and nasal dysfunction after receipt of radioactive iodine (RAI) therapy. We pilot‐tested SALANS among 99 patients with differentiated thyroid cancer (DTC) who received RAI therapy in the past two years. Patients also completed two validated measures: the Xerostomia Inventory¹ (XI) and the Functional Assessment of Chronic Illness Therapy ‐ Spiritual Well‐Being 12 Item Scale² (FACIT SP‐12). We conducted exploratory factor analysis (EFA) to assess the factor structure of the SALANS items and the reliability (internal consistency at group and individual item levels) and validity (convergent and discriminant) of the questionnaire. The final SALANS questionnaire consisted of 33 items and three subscales (salivary, lacrimal, and nasal). Responses were made on a five‐point Likert scale from 0 (Not at all) to 4 (Very much).

Results: Six factors within the three subscales were extracted by EFA on the SALANS questionnaire (three Salivary: 1, α = 0.88; 2, α = 0.87; 3, α = 0.92; two Lacrimal: 1, α = 0.92; 2, α = 0.87; one Nasal, α = 0.92) accounting for 73.5% of the variance. The reliability coefficients for the three subscales were Nasal (0.921), Salivary (0.929), and Lacrimal (0.913). The total SALANS and SALANS‐ Salivary subscale were each highly correlated with XI scores (r² = 0.73, p < .0001; r² = 0.70, p < .0001, respectively), indicating strong convergent validity. The SALANS‐Lacrimal and SALANS‐Nasal subscales were moderately correlated with XI scores (r² = 0.54, p < .0001; r² = 0.52, p < .0001, respectively). The total SALANS was weakly correlated with the FACIT SP‐12 score (r² = 0.14, p = .001) as did the SALANS subscales, indicating divergent validity: Salivary (r² = 0.13, p = .003), Lacrimal (r² = 0.12, p = .003), and Nasal (r² = 0.08, p = .04).

Discussion/Conclusion: The SALANS is a reliable and valid patient‐reported instrument to assess the frequency/timing of symptoms experienced by patients with DTC after RAI therapy. Future directions include assessing the impact of salivary, lacrimal and nasal symptoms on health‐related quality‐of‐life among patients with DTC who receive RAI therapy.

HIGHLIGHTED POSTER 107

Thyroid Cancer Basic Highlighted Poster

BRAF ALTERATIONS ARE LINKED TO CHANGES IN THYROID CANCER MOTILITY AND CONTRACTILITY IN NANOFIBROUS SUBSTRATES WITH TUNABLE FIBER SPACING AND DUROTACTIC REGIONS

Christian Hernandez‐Padilla*¹, Michele Scheerer¹, Zachary Spangler¹, Amrinder Nain², Aime Franco¹

¹Children's Hospital of Philadelphia, USA,²Virginia Tech, USA

The activation of epithelial to mesenchymal transition (EMT) pathways is strongly correlated to the stiffening of the tumor microenvironment. Thus, metastatic progression could be linked to cell durotactic responses, however, limited studies have been able to show this in vitro or in vivo1. To this end, we created nanofiber composite substrates using polystyrene (PS) and polyurethane (PU) to create regions of higher and lower stiffness which were characterized via atomic force microscopy nanoindentations2. Using ImageJ cell tracking tools we were able to ascertain differences in cancer motility of various Braf‐driven cell lines, correlated with different stages of tumor progression. Our 6 independent mouse Braf cell lines have been categorized into epithelial and mesenchymal phenotypes through expression of EMT markers.

Initially, we confirmed that BRAF alterations in cells responded to changes in fiber spacing similarly to previously reported studies with HRAS cell lines3, with faster and more persistent migration. Subsequently, the variation of the mechanical properties revealed that mesenchymal BRAF cells (BB1845) migrated faster in stiffer PS scaffolds. Interestingly, BB1845s cells showed elongated morphology with lower circularities, larger projected areas, and higher MSD diffusion exponents in stiffer substrates. Furthermore, BB1845s showed a stronger durotactic response oriented in the direction of stiffer PS fibers. On the other hand, epithelial phenotypes (BB19) migrated faster on softer PU scaffolds, while having larger areas, coupled with high aspect ratios, long protrusions, and consequently higher MSD exponents. Additionally, we correlated differences in the expression of immunofluorescent vimentin and actin, which were proportional to the regional fiber stiffnesses. Moreover, by using nanonet force microscopy we observed BB1845s exerted 250nN higher forces than other BRAF groups indicating the significant effect of EMT on cell contractility.

Overall, from our study, we are reporting the impact of Braf alterations in cytoskeletal differences which are linked to contractile differences as well as motility changes depending upon the fiber stiffness. By creating suspended fibers with different regional stiffnesses we can continue to elucidate the potential pathophysiological effects of the surrounding ECM in driving epithelial‐to‐mesenchymal transitions that can lead to metastasis.

HIGHLIGHTED POSTER 108

Pregnancy and Development Basic Highlighted Poster

GESTATIONAL HYPOTHYROXINEMIA INDUCES AN ACUTE INFLAMMATORY STATE AT THE MATERNAL‐FETAL INTERFACE AND PRODUCES AN AUTISTIC‐LIKE PHENOTYPE IN THE OFFSPRING WITH MORE ACCENTUATION IN MALES

Enrique González‐Madrid*^1,2, Ma. Rangel‐Ramírez^1,2, Ignacio Cancino^3,4, Claudia Riedel^1,2

¹Laboratorio Endocrino‐inmunología. Facultad Ciencias de la Vida. Universidad Andrés Bello, Chile,²Instituto Milenio Inmunología e inmunoterapia (IMII), Chile,³Universidad Mayor. Center for integrative biology., Chile,⁴Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas, Chile

Objective: Retrospective cohort studies have established that gestational hypothyroxinemia (HTX) increases the offspring's predisposition to present autistic traits. However, there is no exhaustive evidence regarding the cellular and molecular features associated with autism in this offspring. Thus, we aimed to analyze characteristics of an autistic‐like phenotype in the adult mice offspring gestated under maternal HTX (HTX offspring). Furthermore, Maternal Immune Activation (MIA) models show that maternal inflammation at the maternal‐fetal interface in early pregnancy increases the offspring's predisposition to autism. Thus, we evaluated whether gestational HTX also induces inflammation at the maternal‐fetal interface as in the MIA models.

Methods. Gestational HTX was induced in pregnant mice (C57BL/6) by adding methimazole (MMI) in the tap drinking water during embryonic days (E)10 to E14 (Pregnant HTX). A second group received MMI and daily T₄ administration (Pregnant HTX + T₄ ). A third group received only tap drinking water (Pregnant Euthyroid). Pregnant mice were euthanized on E14, the placenta, uterus, and decidua were isolated, and proteins were extracted from these tissues to quantify anti and pro‐inflammatory cytokines by sandwich ELISA. Furthermore, leukocytes were purified, and immune cell populations were analyzed by flow cytometry. Also, different patterns of neuronal populations were assessed in fetal brains by immunofluorescence. In addition, adult progenies from each treatment were subjected to analyze autistic‐like behavior tests. Cytokines and immune cell populations were evaluated by ELISA and flow cytometry, respectively. The relative expression of specific glutamatergic proteins and the proportion of dendritic spines were determined by western blot and Golgi‐cox staining, respectively, particularly in the prefrontal cortex and hippocampus.

Results. We found increased signs of inflammation at the maternal‐fetal interface of the Pregnant HTX mice, as compared to the control groups. In addition, brains from fetuses gestated under maternal HTX were more enriched in different neuronal populations which were in a higher proportion than the controls. On the other hand, the HTX offspring displayed an autistic‐like behavior and also increased traits of inflammation which were both features more accentuated in males. Furthermore, they showed elevated expression of glutamatergic proteins, and a higher proportion of immature dendritic spines, as compared to controls.

Conclusion. Gestational HTX generates an acute inflammatory state at the maternal‐fetal interface, while the offspring displays an autistic‐like phenotype more accentuated in males. This research points to the relevance of maternal thyroid function evaluation during early pregnancy.

HIGHLIGHTED POSTER 109

Health Disparities/Health Equity Clinical Highlighted Poster

IMPROVING MANAGEMENT OF CONGENITAL HYPOTHYROIDISM THROUGH QUALITY IMPROVEMENT CYCLES

Jordan Ross*, Elisha McCoy, Grace Nelson

University of Tennessee Health Science Center, USA

Objective: Thyroid hormone is important for growth and neurocognitive development in young children. We aim to increase the percentage of young patients with congenital hypothyroidism (CH) with a thyroid stimulating hormone (TSH) level in the normal range by 15% within twelve months at Le Bonheur Children's Hospital.

Methods: The medical records of patients with CH were assessed on a rolling monthly basis for TSH levels drawn in‐house or remotely. The six‐month interval prior was considered “in‐range” if a TSH value in that period was in the normal range for the in‐house assay. For each month evaluated, patients were ages 0.5 years to 3.5 years and had started levothyroxine before six months of life. Transient and central hypothyroidism were excluded.

We applied quality improvement (QI) methodology to increase the portion of young children with CH in adequate biochemical control. The initial interventions included a templated message sent from nurses to providers if an eligible patient missed an appointment (begun in October 2022), a workshop for providers to review international recommendations for evaluating patients with CH every three months until three years of age (December 2022), and a strategy for arranging two follow‐up appointments in succession to assure regular access to care (April 2023).

Results: To date, 88 young children with CH have been followed. During the baseline period (February‐September 2022), a mean of 59% (median 58.4%) of patients had an in‐range TSH value during the rolling six‐month intervals. From the start of the first PDSA cycle through May 2023, the monthly outcomes were all above the baseline median, ranging from 62.5% to 68.7% (median 66.2%). There was also an upward trend from November 2022 to March 2023.

At baseline, the average percentage of White children with an in‐range TSH was 70.5% (compared to 47.6% for Black children). Since the start of intervention, the average percentage of Black children with a normal TSH has increased to 62.2% while remaining stable in White children (73.2%).

Discussion: Targeted nursing follow‐up for young patients with CH and a departmental review of guideline‐directed evaluation were associated with improved biochemical control for young patients with CH. The QI changes made at the departmental level appeared to improve biochemical control in Black patients more than White patients, effectively improving a previously unexamined healthcare racial inequity within our population.

HIGHLIGHTED POSTER 110

Thyroid Cancer Clinical Poster

ASSOCIATION BETWEEN SERUM THYROID STIMULATING HORMONE (TSH) AND CANCER RECURRENCE AMONG ADULT PATIENTS WITH DIFFERENTIATED THYROID CANCER (DTC): A RETROSPECTIVE COHORT STUDY

Judy Qiang*¹, Karl Everett², Antoine Eskander¹, Rinku Sutradhar², Afshan Zahedi³, Iliana Lega³, Lorraine Lipscombe³

¹Sunnybrook Health Sciences Centre, Canada,²ICES, Canada,³Women's College Hospital, Canada

Objective: The primary objective was to determine whether exposure to serum thyrotropin (TSH) in the higher normal range (2‐4 mIU/L) was associated with higher disease recurrence than serum TSH in the lower normal range (0.5‐ ≤2 mIU/L). The secondary objective was to evaluate the association between serum TSH exposure and non‐cancer outcomes of atrial fibrillation, stroke, fractures, and all cause death.

Methods: This was a retrospective cohort study of adult differentiated thyroid cancer (DTC) patients who underwent thyroidectomy in Ontario from 2007 to 2018 using linked, administrative health databases. Multivariable Cox proportional hazard regression analyses adjusted for competing risk of death were performed to evaluate the association between serum TSH and time to recurrence and non‐cancer outcomes, with TSH treated as a time‐varying exposure. Disease recurrence was defined as any recurrence requiring repeat surgery and/or radioactive iodine (RAI), and/or DTC specific death.

Results: Exposure to serum TSH 2‐4 mIU/L was associated with a similar composite recurrence rate compared to TSH 0.5‐2 mIU/L overall (adjusted hazard ratio, aHR 1.08, 95% confidence interval, CI 0.89‐1.32), but was associated with a higher composite recurrence in the subgroup who underwent total thyroidectomy and RAI (aHR 1.48, 95% CI 1.01‐2.04). Compared with serum TSH of 0.5‐2 mIU/L, serum TSH <0.5 mIU/L or 4‐10 mIU/L or >10 mIU/L was associated with an increased recurrence (aHR 1.53, 95% CI 1.33‐1.77, aHR 3.10, 95% CI 2.59‐3.71, and aHR 18.5, 95% CI 16.0‐21.3, respectively). Exposure to TSH <0.5 mIU/L was not associated with higher rates of atrial fibrillation, strokes, or fractures.

Conclusion: Our findings suggest that serum TSH targets may be safely liberalized to 0.5‐4 mIU/L without increased recurrence for most DTC survivors. However, for those with more aggressive disease subjected to total thyroidectomy and RAI, a serum TSH target in the lower normal range (0.5‐2 mIU/L) may reduce the risk of recurrence.

HIGHLIGHTED POSTER 111

Thyroid Hormone Action Metabolism and Regulation Basic Highlighted Poster

EXPLORING THE EFFECTS OF THYROID HORMONES ON OLIGODENDROCYTE PROGENITOR CELL DIFFERENTIATION FOR POTENTIAL THERAPEUTIC USE IN MYELIN REPAIR

Ziyu Zhu*, Rashmi Binjawadagi, Jenna Williams, Hiroko Kobayashi, Achala Dharmasiri, Matt Zupan, Meredith Hartley

University of Kansas, USA

Objective: Oligodendrocytes play a critical role in proper nervous system function, and their dysfunction has been linked to various neurological disorders, including multiple sclerosis. Thyroid hormones (TH) stimulate oligodendrocyte progenitor cell (OPC) differentiation, promoting myelination during development, but their effects on OPCs in the adult brain following myelin damage are not fully understood. This study aimed to identify a tolerated TH dose for potential therapeutic use in remyelination and explore the pathways involved in TH action.

Methods: We used an induced conditional knock‐out Myrf^{fl/fl; Plp1}‐CreERT (iCKO‐Myrf) genetic mouse model to identify a tolerated TH dose that improves myelination without disrupting the OPC pool. We assessed the effects of the tolerated dose on neural stem cells and OPCs using weight and scores, behavioral assessments (rotarod and challenge ladder), immunofluorescence, and myelin histology. Additionally, we treated OPCs isolated from P7‐8 Sprague‐Dawley rats with TH to promote differentiation. Single‐cell RNA sequencing was performed on day 4 of differentiation, and transcriptomic profiles were analyzed to identify the pathways involved in TH regulation of OPC differentiation.

Results: In the 10‐week experiment, the 0.06 ppm T3 treatment was identified as a tolerated T3 dose; it showed trends similar to the untreated control group for both weight and score parameters. Myelin histology analysis on the perfused brain and spinal cord samples was performed to analyze the effect of 0.06 ppm T3 on remyelination. Immunofluorescence analysis was performed to analyze oligodendrocyte lineage cells. Based on transcriptomics data, 162 KEGG pathways and 24 Gene Ontology biological processes were identified as involved in T3 action.

Discussion: The preliminary results from iCKO‐Myrf genetic mouse model demonstrated a tolerated T3 dose that could potentially be used in the T3 treatment of demyelination, which will be validated in our 24‐week studies. Furthermore, we identified a panel of genes and pathways regulated by T3 that were associated with OPC differentiation. We plan to validate the key pathways with follow‐up experiments. These findings may provide novel insights into the mechanisms underlying TH‐induced OPC differentiation and may lead to the development of new therapeutic strategies for demyelination disorders.

HIGHLIGHTED POSTER 112

Thyroid Hormone Action Metabolism and Regulation Basic Highlighted Poster

THE IMPACTS OF TRΑ1 E403X MUTATION ON THE CENTRAL NERVOUS SYSTEM OF MICE BASED ON MULTIOMICS ANALYSIS

Yang Li*, Xiaochun Teng, Weiping Teng, Zhongyan Shan, Yingxin Fang, Pingping Dang, Yue Liang, Defa Zhao, Ranran Wang, Yue Xi, Dan Zhang, Wei Wang

Department of Endocrinology and Metabolism, Institute of Endocrine , NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases,The First Hospital of China Medical University, China

Objective: Thyroid hormones are essential for the development of the central nervous system, and TRα1, as the main receptor of thyroid hormones in the central nervous system, plays an important role. Mutation of TRα1 leads to severe developmental defects in the central nervous system. This study aims to investigate the effects of the TRα1 E403X mutation on the central nervous system.

Methods: Brain cortex and hippocampus tissues were extracted from both Thra1^+/+ and Thra1^E403X/E403X littermate mice for proteomic analysis and whole‐transcriptome sequencing on the respective tissue types, and Nissl staining was used to observe the structure of the cerebral cortex and hippocampus. Long‐term potentiation was performed, and some differentially expressed genes were verified by PCR, and some differentially expressed proteins were verified by western blot.

Results: Compared with Thra1^+/+ mice, Thra1^E403X/E403X mice showed delayed physical development and decreased motor and cognitive abilities. Under a microscope, the cerebral cortex was thinner, structurally disordered, and the number of neurons was reduced; the thickness of the hippocampus was reduced, and the arrangement of neurons was disordered, and long‐term potentiation was significantly reduced. The differentially expressed genes in the cerebral cortex proteomics and hippocampal transcriptome could be divided into three parts: the proliferation and differentiation‐related pathways were highly expressed, including ribosomes, nucleosomes, splicesomes, and proteasomes, compared with Thra1^+/+ mice; the pathways related to cell functions were lowly expressed, including ion channels, oxidative phosphorylation, myelin formation, axonal growth, and synaptic function; Multiple death pathways were hyperactivated, including apoptosis, autophagy, pyroptosis, and ferroptosis, which indicated that the central nervous system of Thra1^E403X/E403X mice had developmental delay and premature death. Some key proteins and differentially expressed genes were selected for Western blot and PCR verification.

Conclusion: The potential mechanism for the damage of the central nervous system in mice caused by the TRα1 E403X homozygous mutation is the simultaneous occurrence of developmental delay and premature death, which may explain the structural abnormalities and functional disorders of most nervous systems.

HIGHLIGHTED POSTER 113

Thyroid Hormone Action Metabolism and Regulation Basic Highlighted Poster

THYROID AND THE BRAIN ‐ TSH ENHANCES NEURITE OUTGROWTH

Maryam Mansoori*, Rauf Latif, Terry Davies

Thyroid Research Unit, Icahn School of Medicine at Mount Sinai and the James J Peters VA Medical Center, USA

Background: The extra‐thyroidal effects of TSH have been reported in several tissues including the brain where TSH receptor (TSHR) expression has been documented in specific locations. However, the biologic action of TSH on neuronal cells remains poorly characterized. SH‐SY5Y human neuroblastoma cells have long served as a useful model for neuronal analysis since they can be effectively differentiated into neuronal cells of differing types using cocktails of promoter molecules. We, therefore, investigated whether TSH interacted with such cells.

Objectives: The initial objectives of our study were to examine potential TSHR expression in differentiated SH‐SY5Y neuronal cells and determine their primary and secondary neurite growth characteristics.

Methods: We used an 18 day differentiation period with gradual depletion of FBS in neuronal basic growth media supplemented with retinoic acid, BDNF and db‐CAMP which differentiated 100% of these cells into neurons. TSHR mRNA and protein expression were detected using ddPCR, flow cytometry and immunostaining. Quantification of neurite count at three different time‐points of differentiation was performed on DAPI stained images using Autoneurite and Image J. software.

Results: Cell differentiation resulted in an effective network of neurons with primary, secondary and tertiary neurite outgrowth. FACS analysis confirmed TSHR expression in ∼22.9% of cells by day 18 of differentiation compared to <5 in the undifferentiated cells. Absolute quantification of TSHR mRNA levels revealed ∼1864 copies/ul of cDNA compared to ∼18.7 copies in undifferentiated cells. The majority of TSHRs were localized to the cell body with extended expression on primary neurites as seen using TSHR mAb MC‐1 and neuronal cytoskeletal marker SMI‐31. Furthermore, we observed a significant increase in the count of primary and secondary/tertiary (S/T) neurites when cultured with TSH (up to 1mU/ml) – from 5.01 ± 0.42 and 10.57 ± 0.5 for primary and S/T count in untreated cells compared to 11.42 ± 0.9 and 33.51 ± 6.8 in TSH treated cells (p = 0.0003 and 0.02 respectively).

Conclusions: These data confirm functional TSHR expression in these fully differentiated neurons as illustrated by significant enhancement of neurite outgrowth. This model will allow further characterization of TSHR modulation of neuronal activity.

HIGHLIGHTED POSTER 114

Disorders of Thyroid Function Clinical Highlighted Poster

COST‐EFFECTIVENESS OF A DIGITAL THERAPEUTIC FOR MANAGING HYPERTHYROIDISM: EVALUATION OF GLANDY^TM

Junghyun Kim¹, Jaemin Park², Jaeyong Shin^3,4, Kyubo Shin*², Jae Hoon Moon^2,5,1

¹Center for Artificial Intelligence in Healthcare, Seoul National University Bundang Hospital, Korea, Republic of,²THYROSCOPE INC., Korea, Republic of,³Department of Preventive Medicine, Yonsei University College of Medicine, Korea, Republic of,⁴Institute of Health Services Research, Yonsei University, Korea, Republic of,⁵Department of Internal Medicine, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Korea, Republic of

Background: We have developed a digital therapeutics called Glandy^TM that is designed to manage thyroid dysfunction. GlandyTM has two key functions: predicting thyroid dysfunction using the user's heart rate (HR) monitoring data from wearables, and predicting inflammatory active thyroid‐associated ophthalmopathy (TAO) based on the user's facial image. In this study, we evaluated the cost‐effectiveness of adopting Glandy^TM in the management of hyperthyroidism.

Method: The cost‐effectiveness analysis of hyperthyroidism in 40‐year‐old individuals was based on a lifetime decision analytic model consisting of a decision tree and a joining Markov model. Event probabilities and model parameters were derived from clinical trials, the national health insurance claims data in Korea, and published literature. Quality‐adjusted life years (QALY) was the outcome measure to estimate the incremental cost‐utility (ICUR) ratio. Sensitivity analyses were performed to assess the impact of essential model assumptions and to determine the relative effect of individual parameters.

Results: Hyperthyroidism management with digital therapeutics of Glandy^TM, THYROSCOPE INC. was associated with both higher costs (₩43,042,503 vs. ₩32,246,909) and benefits [QALY (28.348 vs. 26.346)], with an ICUR of ₩5,391,963/QALY, compared to standard care. The probabilistic sensitivity analysis (PSA) demonstrated that this digital monitoring solution for hyperthyroidism would have an estimated probability of 100% cost‐effectiveness at a conservative willingness‐to‐pay of $30,000/QALY.

Conclusion: Glandy^TM is the first digital therapeutic designed for managing thyroid dysfunction. By using Glandy^TM, patients can monitor their thyroid function state using HR data from wearables and detect referable active TAO early with their digital facial images. It is expected that the adoption of this solution will be cost‐effective and provide significant advantages in the treatment of hyperthyroidism.

HIGHLIGHTED POSTER 115

WITHDRAWN

HIGHLIGHTED POSTER 116

Thyroid Imaging Clinical Highlighted Poster

DIAGNOSTIC ACCURACY OF ULTRASOUND IN PREDICTING EXTRATHYROIDAL EXTENSION AND ITS RELATION TO BODY MASS INDEX IN A NORTH AMERICAN POPULATION

Rohit Namala*¹, Mahmoud Omar¹, Peter Issa², Bryce Christensen¹, Kavin Sugumar¹, Neel Gupta³, Mohamed Shama¹, Eman Toraih^1,4, Emad Kandil¹

¹Department of Surgery, School of Medicine, Tulane University, USA,²School of Medicine, Louisiana State University Health Sciences Center, USA,³Department of Radiology, School of Medicine, Tulane University, USA,⁴Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Egypt

Detection of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) influences treatment plans and surgical aggressiveness. Ultrasound (US) is the long‐standing preoperative imaging method of choice. Recent literature from Asia suggests that patient characteristics, such as body mass index (BMI), influence US accuracy. Here, we examine the effect of BMI on the accuracy of US at a North American tertiary referral center. A total of 204 PTC‐confirmed patients were retrospectively read by a radiologist blinded to surgical pathology findings. The radiologist recorded multiple sonographic features, including ETE, loss of echogenic capsule, nodule vascularity, capsular abutment, and bulging of contour. When considering all patients, the ultrasonographic feature with the best overall performance was the loss of the echogenic capsule (diagnostic odds ratio (DOR) = 4.48, 95% confidence interval (CI) = 1.86‐10.78). Sub‐group analysis by patient BMI found that area under the curve (AUC) for sonographic features was greater in non‐obese BMI patients (0.71 ± 0.06) when compared with obese patients (0.43 ± 0.05; p = 0.001). Overall, US diagnostic performance was significantly better in non‐obese (DOR = 3.70, 95%CI = 1.53‐8.94) patients when compared to those who were obese (DOR = 1.12, 95%CI = 0.62‐2.03; p = 0.03). Loss of the echogenic capsule did not differ between the two cohorts with respect to DOR (p = 0.51), specificity (p = 0.52), or sensitivity (p = 0.09). Our work suggests that the diagnostic value of ETE detection by US is impaired in obese patients. Considering that loss of the echogenic capsule did not differ with respect to diagnostic performance, specificity, nor sensitivity between non‐obese and obese patients, it could be regarded as the most critical predictor of US‐determined ETE.

POSTER 391

Autoimmunity Basic Poster

GUT MICROBIOTA MEDIATED THE THERAPEUTIC EFFICACIES OF GLUCOCORTICOIDS IN THE TREATMENT OF GRAVES OPHTHALMOPATHY

Tingting Shi*

Beijing Tongren Hospital, China

Growing evidences indicate that the alterations in gut microbiota are associated with Graves disease and Graves' ophthalmopathy. Glucocorticoids (GCs) are widely used in the treatment of Graves' ophthalmopathy (GO). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs.

Using the 16S rRNA technique, we investigated the differences between the gut microbiota associated with the immune cytokines of GO and relevant glucocorticoid treatment in a cohort of 25 subjects with (GO‐G). Then 25 GO patients undergone pulse glucocorticoid treatment (GO+G). According to the glucocorticoid therapeutic efficacy, patients were divided into effective group (effective) and non‐effective group (non‐effective). We observed that the diversity and structure of the microbial community in GO + G patients were significantly changed compared to that of GO‐G patients, whereas the gut microbia of the effective group showed significant difference with the non‐effective group, which implicate that the shift in the gut microbiome could represent a good response to glucocorticoid in GO patients. Furthermore, the down‐regulations of cytokines in GO + G patients were closely related to change in the gut microbia community, which indicates that the change of genera in GO patients may play an important role in regulating expression level of immune cytokines. Our analysis of gut microbiota, glucocorticoid therapy, and immune cytokines might provide novel evidence revealing the new treatment of GO patients.

POSTER 392

Autoimmunity Case Study Poster

STEROID‐RESISTANT EUTHYROID EXOPHTHALMOS, MYXEDEMA, AND OSTEOARTHROPATHY (EMO) SYNDROME TREATED WITH RITUXIMAB

Hernessa Hernandez*

Philippine General Hospital, Philippines

Introduction: Exophthalmos, pre‐tibial myxedema, osteoarthropathy with acropachy (EMO/EMA) syndrome is a rare constellation of extra‐thyroidal manifestations of Graves' disease (GD) affecting less than one percent of this population. Due to its low incidence, there is no consensus to its treatment. Rituximab has been recently used for steroid‐ resistant exophthalmos but not in EMO syndrome. Hence, we present this case to describe the rare extrathyroidal manifestations of GD, and share our experience with the use of rituximab.

Case Description: The case is a 57‐year‐old female who was treated with total thyroidectomy for her Graves' disease and developed post‐surgical hypothyroidism replaced with levothyroxine. Three months after her surgery, she developed progressive bilateral exophthalmos, followed by swelling of the interphalangeal joints, with digital clubbing, and a well‐demarcated erythematous thickened plaques and nodules on both legs and feet and debilitating joint pains. She was on high doses of steroid for almost ten years with no clinical improvement. She was examined hypertensive, obese, with moon facie, and central obesity. She had bilateral exophthalmos, with redness and tearing, and swollen eyelids resulting to mechanical ptosis. Her hands showed bilateral swelling in the interphalangeal region associated with finger clubbing and skin tightness, and her lower extremities had a well‐demarcated erythematous thickened plaques and nodules, tender on palpation with the appearance of “orange peel skin”. Her thyroid function tests were normal but her thyroid receptor anti‐bodies (TRAb) assay was highly elevated. She received two doses of 500 mg rituximab infusion. After one month of Rituximab treatment, there was a significant reduction of the TRAb levels, and she was able to ambulate without pain. There was also a significant decrease in the pre‐tibial myxedema and nodules. The exophthalmos persisted, but there were no clinical signs of eye inflammation.

Conclusion: The EMO syndrome is caused by TRAb that cross‐react with the connective tissue and muscle antigens that stimulate fibroblasts and glycosaminoglycan formation. The elevated TRAb levels despite the absence of the thyroid gland, suggest that plasma cells in the thyroid gland are not the major site of autoantibody synthesis. Rituximab, a drug depleting CD‐20 positive B‐cells, can be a treatment option to suppress the TRAb, and consequently, the extra‐thyroidal manifestations of GD.

POSTER 393

Autoimmunity Case Study Poster

FIRST EPISODE OF THYROTOXIC PERIODIC PARALYSIS IN THE SETTING OF NEWLY DIAGNOSED GRAVES' DISEASE

Bolin Chang*¹, Shuhei Hattori¹, Mayumi Fernandez², Keisuke Miyamoto³

¹University of Hawaii Internal Medicine Residency Program, USA,²University of Hawaii Pathology Residency Program, USA,³University of Hawaii John A. Burns School of Medicine, USA

Introduction: Thyrotoxic periodic paralysis (TPP) is a sporadic form of hypokalemic periodic paralysis characterized by recurrent episodes of muscle weakness and hypokalemia in association with hyperthyroidism. TPP often presents in the second to fourth decades of life and has the highest incidence among East Asian males. Here, we report a case of a first episode of TPP in the setting of newly diagnosed Graves' disease.

Description of the Case: A 34‐year‐old Vietnamese male presented with a two‐week history of intermittent bilateral lower extremity muscle cramps that progressed to acute paraparesis. This was preceded by two months of mild hyperthyroid symptoms and an episode of self‐limiting flu‐like symptoms one month prior. He denied prior neck radiation or supplement use and was a never‐smoker. Family history was negative for thyroid disease and malignancy. Physical examination revealed a soft but moderately enlarged thyroid gland without palpable nodules, a fine bilateral resting hand tremor, and bilateral leg weakness with preserved tone, reflexes, and sensation. No exophthalmos or skin changes were noted. Laboratory evaluation revealed low K+ (1.8 mEq/L) and TSH (<0.07 uIU/mL); elevated FT4 (4.6 ng/dL), TT3 (401 ng/dL), and FT3 (18.6 pg/mL); and the presence of both TSI and TBII. His K+ was replaced with subsequent improvement in his leg weakness. Neck ultrasound revealed a heterogeneous and hypervascular thyroid gland. Thyroid scintigraphy showed diffusely increased radioactive iodine uptake by a large goiter, which was consistent with Graves' disease. Nadolol was started with clinical improvement. Following 131I treatment, the patient returned to a euthyroid state on appropriate weight‐based levothyroxine therapy.

Discussion: TPP is a rare condition whose mechanism is not well understood. In cases of acute paraparesis, clinicians should include TPP in the differential diagnosis, especially with concomitant severe hypokalemia in the absence of common precipitants. Focused history taking is crucial for early diagnosis and appropriate management.

POSTER 394

Autoimmunity Case Study Poster

A RARE CASE OF PENDRED SYNDROME COMPLICATED WITH HYPERTHYROIDISM

Yoshio Nomura*, Mai Ito, Akiko Niiori

Department of Endocrinology and Diabetes, Inazawa Municipal Hospital, Japan

Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness and goiter and is caused by biallelic mutations in the SLC26A4/PDS gene. The thyroid status is generally euthyroid or hypothyroid. Herein, we present a rare case of Pendred syndrome complicated with hyperthyroidism.

Description of the Case: An 18‐year‐old girl with congenital deafness consulted our Department of Otolaryngology for adjustment of her hearing aid. We referred to Department of Endocrinology for a large goitor. Although the thyroid function parameters were normal, we suspected Pendred syndrome due to the presence of goiter and deafness. In view of the positive perchlorate discharge test, we analyzed the SLC26A4/PDS gene. A homozygous His723Arg mutation was detected, confirming Pendred syndrome. although her thyroid function was normal, L‐T4 was administered for 6 years to suppress TSH level and reduce the thyroid volume.

Because she relocated, she was followed up at another hospital. At 27‐years of age, she presented to our hospital with generalized fatigue and finger tremors. Her TSH, FT3, FT4 and TRAb values were 0.01 μIU/mL, >30 pg/mL, 3.24 ng/dL and 21.1 IU/L, respectively. She was diagnosed to have Pendred syndrome complicated with hyperthyroidism. She was treated with methimazole. Her symptoms improved. Methimazole was gradually tapered, and stopped after approximately six months later.

Discussion: We experienced a rare case of Pendred syndrome, exhibiting hyperthyroidism. The thyroid function status in Pendred syndrome is usually euthyroid or hypothyroid. The mechanism of development of hyperthyroidism in this patient is unclear, thus further studies are required to determine the mechanism, especially in terms of immunological aspects.

POSTER 395

WITHDRAWN

POSTER 396

Autoimmunity Case Study Poster

PTU‐INDUCED ANCA‐ASSOCIATED VASCULITIS; A CASE REPORT OF A RARE SIDE EFFECT TWO YEARS AFTER PTU INITIATION FOR GRAVES' DISEASE TREATMENT

Qamar Al Tinawi*, Ghassan Sindi, John Gallagher

Creighton Univeristy, USA

Propylthiouracil (PTU) has been associated with autoimmune syndromes, particularly anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis. Here, we report this rare association.

A 41‐year‐old female presented with a 3‐year history of Graves' disease and orbitopathy. She was treated initially with radioactive I131 but unsuccessfully. Next, she was given Methimazole but developed arthralgias, became non‐compliant and developed thyroid storm. She was considered for Thyroidectomy but was noted to have left vocal cord paralysis, so instead was started on PTU. Two years later, she presented with a rash involving her extremities that progressed to multiple large fluid‐filled bullae measuring 2‐3 inches. At presentation, she was tachycardic and afebrile. Laboratory results showed: serum TSH <0.005 UIU/ml (0.4‐3.8), FT4 0.9 ng/dl (0.7‐1.4), FT3 4.9 pg/ml (2.1‐3.8), CRP 19.6 mg/L (<9.0), ESR 21 mm/hr (0‐20), Creatinine 0.53 mg/dl (0.50‐1.10), p‐ANCA 1:640 (<1:20 Titer), Protein S function 49% (63‐140%), C4 Complement 12 mg/dl (15‐40). Blood cultures were negative. Lupus anticoagulant, protein C, Factor 5 level, C3 Complement level, aPTT, and fibrinogen level were normal. Skin biopsy revealed occlusion of small and medium‐sized blood vessels by fibrin thrombi consistent with thrombotic vasculopathy. She was treated for three days with 500 mg intravenous methylprednisolone followed by a tapering dose of prednisone starting at 60 mg daily which halted the disease progression promptly. After several months she underwent an uncomplicated total‐thyroidectomy and remains on 20 mg of prednisone.

Although ANCA positivity has been reported in 23% of patients on PTU, vasculitis is very rare. Vasculitis can be systemic, involving multiple organ systems, and can be mild or life‐threatening. The type of ANCA positivity may be linked to multiple system involvement. In this case, she only had cutaneous vasculitis with positive p‐ANCA and negative c‐ANCA. The mechanism by which PTU induces vasculitis remains unclear. Alterations in myeloperoxidase activity has been suggested. When triggered, ANCA activates the complement cascade resulting in low C4 complement and activation of the coagulation system leading to vasculitis. In conclusion, PTU‐induced ANCA vasculitis is a rare adverse event that needs intensive treatment with corticosteroids for at least one year.

POSTER 397

Autoimmunity Clinical Poster

MULTIMODAL CORRELATION ANALYSIS OF GRAVES' OPHTHALMOPATHY SEVERITY GRADINGS IN 594 CHINESE CASES

Tianyi Zhu*, Chenlin Yang, Yi Wang, Xuefei Song, Jing Sun, Huifang Zhou

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China

Objective: Graves' ophthalmopathy (GO) is the most common orbital disease in adults, causing deteriorations in appearance and visual acuity. Extremely severe form of GO leads to irreversible vision loss and even blindness which considerably reduce the life quality of patients. This retrospective and cross‐sectional study was designed to investigate the factors associated with severity of GO to predict the incidence of extremely severe GO and promote early intervention.

Methods: Clinical data including demographics, chief complaints, ophthalmic evaluations, thyroid function tests, orbital imaging examinations and treatment history of GO patients at their onset stage of disease were collected and compared among mild, moderate‐to‐severe and extremely severe GO patients to reveal factors associated with severity of GO and further predict extremely severe GO.

Results: A total of 594 GO patients including (1080 eyes) were retrospectively analyzed. Descriptive analysis indicated that the peak age of onset was 45‐50 years old for female and 51‐55 years old for male. There were 117 mild cases (19.70%), 272 moderate‐to‐severe cases (45.79%), and 205 very severe cases (34.51%). According to the clinical activity score (CAS), there were 284 active cases and 310 stable cases. Chief complaints focused on eyelid swelling (91.58%), exophthalmos (87.54%) and eyelid retraction (62.29%). Correlation analysis showed that the severity of GO was higher in male than in female (P < 0.001) and associated with smoking (P = 0.039). The average age of patients with dysthyroid optic neuropathy was 53.79 ± 12.45, higher than that of mild and moderate‐to‐severe patients (P < 0.001). The severity was also significantly related to ophthalmic examination indicators including Margin reflex distance 2 (MRD2), proptosis, Best‐Corrected Distance Visual Acuity (BCVA), CAS, eye movement disorders and diplopia score. thyrotropin receptor antibody (TRAb) and thyroid peroxidase antibody (TPOAb) in serology test was also correlated with GO grading.

Conclusion: Patients characterized by male, older age, smoking, worse ophthalmic examination indicators and higher levels of TRAb and TPOAb are more prone to severe GO. This study paints a panoramic picture of GO patients and will promote early diagnose in predicting severe GO.

POSTER 398

Disorders of Thyroid Function Basic Poster

THE IMPACT OF CIRCADIAN RHYTHM DISTURBANCE ON THE HPT AXIS IN RATS

Cihang Lu, Weiping Teng, Zhongyan Shan, Tingting Liu, Zheyu Lin*, Ying Sun, Lijun Tian, Bo Song

Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, China

Abstract

Objective: In recent years, the increasing average level of thyroid‐stimulating hormone (TSH) and the rising prevalence of subclinical hypothyroidism in the population have become an undeniable phenomenon. Abnormal sleep and circadian rhythm disorders are considered to be one of the causes. This article aims to analyze the impact and mechanism of circadian rhythm disorders on the hypothalamic‐pituitary‐thyroid (HPT) axis.

Methods: A light‐dark disturbance model was constructed in male Wistar rats to detect the levels of serum melatonin, thyrotropin‐releasing hormone (TRH), TSH, and thyroid hormones, as well as the expression levels of genes related to the biological clock and hormone synthesis in the HPT axis. CUT & TAG sequencing was performed on the CLOCK gene in rat thyroid. CLOCK overexpression, silencing, and gradient concentration TSH intervention were performed in human normal thyroid cell line N‐thy‐ori to detect the expression levels of genes related to the biological clock and hormone synthesis.

Results: Compared with the normal group, the rhythms of melatonin, TRH, TSH, and thyroid hormones were disturbed in rats subjected to light‐dark disturbance for 3 weeks and 3 months. The TSH and TT3 levels in the 3‐week light‐dark disturbance group were normal, but the TSH level in the 3‐month light‐dark disturbance group increased and the TT3 level decreased. There were no differences in the levels of melatonin, TRH, and TT4 among the groups. In the 3‐month light‐dark disturbance group, the expression levels of genes related to the biological clock and hormone synthesis in the HPT axis were abnormal and rhythmically disturbed. CUT&TAG sequencing identified the CLOCK transcriptional regulatory gene in rat thyroid. In vitro, when CLOCK was silenced, the expression levels of PAX8 and SLC5A5, CLOCK‐regulated genes, decreased, while the expression levels of PAX8 and SLC5A5 increased when CLOCK was overexpressed.

Conclusion: Long‐term disruption of the circadian rhythm can lead to disturbance in HPT axis.Abnormal thyroid function due to circadian rhythm disorder may be partially due to upstream HPT axis signal disturbance and partially due to thyroid self‐biological clock disturbance.

POSTER 399

Disorders of Thyroid Function Translational Poster

ADVANCING THYROID FUNCTION TESTING IN CDC STANDARDIZATION PROGRAMS

Uliana Danilenko*¹, Ashley Ribera¹, Otoe Sugahara¹, Tatiana Buchannan¹, David Spector^1,2, Samantha Knoblock^1,2, Lynn Collins^1,3, Lindsey Long⁴, Norma Vazquez⁴, Li Zhang¹, Hubert Vesper¹

¹CDC, USA,²Oak Ridge Institute for Science and Education, USA,³Cherokee Nation Operational Solutions, LLS, USA,⁴Battelle, USA

Objective: Concerns about the accuracy and reliability of thyroid function tests, especially free thyroxine (FT4), have been stated by the clinical laboratory community for many years. Standardization of FT4 measurements will improve comparability of results among methods and allow for the development of common, evidence‐based clinical guidelines and reference intervals.

Methods: CDC Clinical Standardization Program (CSP) has created the hormone standardization program for FT4 (CDC HoSt‐FT4). CDC HoSt‐FT4 has developed a highly accurate and precise equilibrium dialysis (ED) liquid chromatography tandem mass spectrometry (ID‐LC/MS/MS)‐based reference measurement procedure (RMP) for FT4 and is part of the IFCC reference laboratory network. The RMP assigns reference values to high quality individual donor sera used by CDC HoSt‐FT4. Program participants may use these materials to evaluate the accuracy and reliability of their methods, adjust calibration, and monitor their method's performance over time. Those participants meeting certain analytical performance requirements are considered standardized. To assist with the development of reference intervals that can be used with all standardized assays, CDC developed a high‐throughput routine FT4 method based on ED‐isotope dilution LC‐MS/MS that is standardized to the CDC FT4 RMP.

Results: The intra‐ and inter‐day imprecision of the CDC RMP and FT4 routine methods were within 3.6 % (RMP) and 6.9% (routine), respectively. The CDC RMP mean bias to another established RMP is within 2.5%. The measurement range of both the FT4 RMP and routine methods are suitable for analysis of hypo‐, eu‐, and hyperthyroid patients (1.29–258 pmol/L or 1‐200 pg/mL). The routine method has good agreement with RMP with overall 5.4 % difference between two methods, which is within analytical performance requirements. Initial findings indicate that non‐standardized assays can measure FT4 up to 34% lower than standardized assays.

Discussion/Conclusion: Advancement of thyroid function testing through standardization will improve comparability among assays and facilitate clinical practice and public health.

POSTER 400

Disorders of Thyroid Function Case Study Poster

A SUDANESE CHILD WITH CONGENITAL HYPOTHYROIDISM AND DEAFNESS HOMOZYGOUS FOR SLC26A4 P.TRP482*

Mohammad Islam*¹, Amna Ahmed², Alexandra Dumitrescu³, Roy Weiss¹

¹University of Miami Miller School of Medicine, Department of Medicine, USA,²University of Almughtaribeen, Faculty of Medicine, Department of Paediatrics and Child Health, Sudan,³University of Chicago, Departments of Medicine, USA

Introduction: Screening for monogenic causes of congenital hypothyroidism in the Sudan has revealed mutations in TG, TPO, IYD, DUOX1, DUOX2 and TSHR genes. We present the first case of a SLC26A4 mutation in this population.

Case Description: A 5‐year‐old East Sudanese boy from asymptomatic consanguineous parents was found to have a goiter on routine examination. He was also diagnosed with bilateral sensorineural hearing loss and associated speech difficulties. There was no jaundice, constipation, umbilical hernia or dysmorphic features. Family history revealed a maternal cousin with hearing impairment. The serum TSH was elevated, and the patient was treated with 100 μg L‐T4 with normalization of the serum TSH. The mother has no goiter and normal thyroid function tests. The father was not available for this study. Whole exome sequencing analysis of a panel of thyroid related genes revealed an early termination mutation in the SLC26A4, c.1446G>A, p.Trp482*. Subsequent Sanger sequencing confirmed the proband to be homozygous for this mutation and the mother was heterozygous.

Discussion: This SLC26A4 mutation was previously reported as part of a compound heterozygous defect together with c.304G>A; p.Gly102Arg in a patient with a less severe phenotype and without goiter1. The missense variant p.Gly102Arg in homozygous state was reported to cause non‐syndromic sensorineural hearing loss (SNHL) and Pendred syndrome (PDS). Another affected family homozygous for a pathogenic splice‐site accepter variant was diagnosed with atypical PDS, manifested with deafness only. Additional genotype‐phenotype correlations report compound heterozygous SLC26A4 variants presenting with high frequency hearing loss and enlarged vestibular aqueduct (EVA, Mondini malformation) without goiter, manifesting more severe deafness, earlier age of onset, and more variable hearing levels.

This report extends our understanding of the severity of the phenotypes caused by deleterious bi‐allelic variants in SLC26A4. The identification of a Sudanese subject homozygous for the early truncation mutation, p.Trp482*, indicates that this pathogenic allele is likely prevalent in this population, especially considering that close to 40% of children in Sudan have consanguineous parents. SLC26A4 screening could be a part of the molecular testing for children presenting with congenital or early‐onset SNHL in Sudan.

POSTER 401

Disorders of Thyroid Function Case Study Poster

A CASE OF I¹³¹‐MIP‐1095 INDUCED HYPOTHYROIDISM

Samridhi Patel*¹, Jacqueline Jonklaas¹, Shreedip Patel², Shreejal Patel³, Rachna Goyal¹

¹Medstar Georgetown University Hospital, USA,²Medstar Southern Maryland Hospital, USA,³St Martinus University Faculty of Medicine, Curaçao

Introduction: Radioactive iodine (RAI) labeled with I¹³¹ has been used to treat thyroid disease and thyroid cancer for decades. Radioiodine‐labeled molecules are also used for the treatment of several malignancies like neuroblastoma, Hodgkin lymphoma, pheochromocytoma, etc. I¹³¹‐MIP‐1095 is a radioiodine‐labeled small molecule inhibitor of prostate specific membrane antigen (PSMA). PSMA is expressed by all prostate cancers; it has become an attractive target for its staging and targeted treatment. We describe the case of a patient who developed hypothyroidism after multiple treatments of I¹³¹‐MIP‐1095.

Description: A 72‐year‐old male with past medical history of metastatic prostate cancer who was recently enrolled in the ARROW trial presented with newly diagnosed primary hypothyroidism. It is an open‐labeled, randomized, controlled trial with the aim to study the efficacy of I¹³¹‐MIP‐1095 for metastatic castration‐resistant prostate cancer. Our patient received three treatments of I¹³¹‐MIP‐1095 (100mCi each) over 9 months. Potassium iodide (KI; 1g/mL) 0.3 mL three times a day was prescribed for ten days starting on the day prior to each treatment. Despite the prophylaxis, the patient presented with complaints of weight gain, constipation, fatigue, and lethargy. Thyroid stimulating hormone (TSH) was 48.8 μIU/mL (0.5‐4.7) and free T4 was 0.4 ng/dL (0.89‐1.76). Thyroid peroxidase (TPO) antibody titer was elevated. Symptoms resolved and thyroid function tests normalized after six weeks of treatment with oral levothyroxine 1.6 mcg/kg/day.

Discussion: RAI (like cold iodine) concentrates within thyroid tissue via sodium‐iodide symporter (NIS) followed by oxidation and organification by TPO. I¹³¹ decays with the emission of a β particle causing DNA damage and cell apoptosis. Multiple agents for thyroid prophylaxis are available including KI (dilution of circulating iodine), methimazole (blocks TPO), thyroxine (lowers TSH thereby, lowering RAI uptake), and perchlorate (blocks NIS). While hypothyroidism is well‐described as a late toxicity of I¹³¹‐MIBG treatment in the pediatric population with neuroblastoma, it is not frequently described in studies using I¹³¹‐MIBG for pheochromocytoma, paraganglioma, medullary thyroid cancer, etc ⁽¹⁾. In a study, 28 men with prostate cancer received a single treatment of I¹³¹‐MIP‐1095 (averaging 129 mCi) and sodium perchlorate for thyroid prophylaxis, only one case of hypothyroidism was reported ⁽²⁾. In another study of 36 men who received 1 to 3 treatments of I¹³¹‐MIP‐1095 along with sodium perchlorate, no cases of thyroid dysfunction were reported ⁽³⁾.

POSTER 402

Disorders of Thyroid Function Case Study Poster

A RARE CASE OF PARALYSIS IN THYROTOXICOSIS

Neha Syed*¹, Christopher Para¹, Samantha Storti¹, Nora O'Byrne², Faizan Rahim¹, Adeola Adetunji¹

¹nternal Medicine Residency, Advocate Christ Medical Center, USA,²Department of Endocrinology, Advocate Christ Medical Center, USA

Introduction: Thyrotoxic Periodic Paralysis (TTP) is a rare and sporadic condition characterized by acute onset of paralysis and hypokalemia in a thyrotoxic state. In patients with hyperthyroidism, the high thyroid hormone level increases the responsiveness to beta‐adrenergic stimulation, which along with thyroid hormone itself, increases the activity of skeletal muscle Na‐K ATPase. Potassium is shifted intracellularly resulting in hyperpolarization of skeletal muscle causing inexcitability. TTP can be exacerbated during states of elevated epinephrine or insulin, such as times of increased stress or high carbohydrate intake, leading to further progression of hypokalemia.

Case Presentation: An 18‐year‐old Hispanic male with known Grave's disease presented with generalized muscle weakness, prominently in his proximal lower extremities with inability to ambulate. He had similar episodes after consuming high carbohydrate meals or after vigorous exercise. This current episode was preceded by large amounts of soda the night prior. He was non‐adherent with thiouracil medication. Physical exam showed tachycardia, enlarged thyroid with firm consistency, strength 3/5 in bilateral lower extremities, 4/5 in upper extremities, and intact reflexes. Labs were remarkable for potassium 1.6, TSH <0.008, Free T4 4.8, and Free T3 16.7. TPP was diagnosed after ruling out other possible causes. He was treated with potassium replacement and methimazole. On day two, potassium was 4.9 and weakness had fully resolved.

Discussion: TPP occurs in 0.1‐0.2% of hyperthyroid individuals. It is most common in males of East Asian descent. It is less frequently seen in other ethnicities, such as our patient of Hispanic ethnicity, and it important to recognize and treat urgently. As seen in this patient, TTP has an acute onset of paralysis, commonly affecting proximal muscles symmetrically with lower extremities more than upper extremities. Large carbohydrate consumption and rigorous exercise can trigger episodes of TTP. Other known triggers include stress, trauma, or high sodium intake. Patients who develop TTP should undergo counseling of triggers to decrease future risk of TTP, including nutritional and exercise guidance. This is crucial as TTP can be life‐threatening due arrhythmias and weakness of respiratory muscles requiring ventilatory support. Adherence to thiouracil medication is also critical because euthyroidism prevents TPP attacks.

POSTER 403

Disorders of Thyroid Function Clinical Poster

TRIALS EXAMINING THE SAFETY AND EFFICACY OF NORTH STAR DESICCATED THYROID EXTRACT: PHASE 1 RESULTS AND STUDY DESIGN OF THE PHASE 2 TRIAL

Ahmad Al‐Sabbagh*¹, Jeffrey Garber², Elizabeth McAninch³, Srihari Vedartham¹, Thanh Hoang⁴, Allen Fields¹, Antonio Bianco⁵, Samuel Testino¹, David Robertson⁶, Irwin Klein⁷, Francesco Celi⁸

¹Avion Pharmaceuticals, USA,²Harvard Vanguard Medical Associates, USA,³Stanford University Medical Center, USA,⁴Walter Reed National Military Medical Center, USA,⁵University of Chicago, USA,⁶Piedmont Hospital, USA,⁷Private Practice, USA,⁸Virginia Commonwealth University, USA

Objective: There has been renewed interest in treatments for hypothyroidism containing T3, particularly for patients with persistent hypothyroid symptoms despite optimized levothyroxine (LT4) treatment, prompting the need for randomized controlled trials in this area. Here we present the clinical development program of North Star, a desiccated thyroid extract (DTE) that aims to safely and effectively address unmet needs for patients with hypothyroidism.

Methods: Forty‐five healthy volunteers participated in the phase 1, 4‐arm, crossover, dose proportionality study. In the 3 active arms, subjects received 360 mg of DTE in 15‐mg, 60‐mg, and 120‐mg tablets, supplemented with placebo tablets. The 4th arm consisted of placebo tablets only. The phase 2 multicenter, randomized, double‐blind, parallel‐group trial will evaluate dose conversion from LT4 to North Star DTE in adults (N = 300) with primary hypothyroidism randomized 2:1 to DTE or LT4 for 30 weeks, followed by an optional 24‐week open‐label extension period (NCT05712421). Dose will be evaluated every 6 weeks for the first 18 weeks, followed by a 12‐week stable‐dose period. The primary endpoint is the ratio of LT4 dose at screening to DTE dose required at the end of treatment period to achieve and maintain normal TSH levels. Secondary and exploratory endpoints include proportion of patients with TSH within normal range at the end of treatment, adverse events (AEs), T4/T3 ratio, total T4, free T3, total T3, ThyPRO‐39, and NIH Toolbox Cognitive Battery scores.

Results: In the phase 1 trial, baseline‐adjusted C_max for T3 for the 15‐mg, 60‐mg, and 120‐mg tablets were 2.8, 2.9, and 2.8 ng/mL, and for T4 were 37.5, 37.4, and 38.7 ng/mL, respectively, demonstrating dose equivalency. Similarly, baseline‐adjusted AUC_0‐48 for T3 were 27.8, 28.2, and 29.1 h*ng/mL, and for T4 were 649.1, 652.2, and 720.5 h*ng/mL, respectively. A comparable TSH decrease was seen across all dosage strengths. AEs, which were mostly mild in severity, were not significantly different across the study arms. The phase 2 trial is underway, and completion of the blinded period is expected in June 2024.

Discussion: These trials will help delineate safe and effective utilization of North Star in treating hypothyroidism.

POSTER 404

WITHDRAWN

POSTER 405

Disorders of Thyroid Function Clinical Poster

IMPENDING THYROID STORM IN PREGNANCY ‐ A DILEMMA BETWEEN GESTATIONAL TRANSIENT THYROTOXICOSIS VS NON‐HCG MEDIATED THYROTOXICOSIS

Mouna Gunda*¹, Arya May¹, Maria Riofrio², Danica Vodopivec¹

¹University of Alabama at Birmingham, USA,²Universidad San Franscisco de Quito, Ecuador

Introduction: Hyperthyroidism in pregnancy has an incidence of only 0.1‐4% and can be hCG mediated or non‐hCG mediated. Etiology of hCG‐mediated hyperthyroidism is gestational transient thyrotoxicosis (GTT), multiple gestation, trophoblastic disease and familial hypersensitive TSH receptor. We describe a pregnant patient presenting with impending storm due to GTT associated with hyperemesis gravidarum (HG) that resolved after decline in β‐hCG.

Description of case: A 20‐year‐old woman at 15‐weeks of gestation with singleton pregnancy presented with nausea, vomiting, dehydration, weakness, weight loss and diarrhea for two weeks. She had no prior history of thyroid or other autoimmune disease. Vitals were unremarkable, except mild tachycardia. Examination revealed confusion, dry skin, tremors, hyperreflexia, normal thyroid gland without palpable nodules and no signs of thyroid eye disease. Labs revealed β‐hCG: 425,693 mIU/mL (4,834‐122,037mIU/mL at 15‐weeks' gestation), TSH undetectable, fT4: 4.56 ng/dL (0.58‐1.64ng/dL), fT3: 5.4 pg/mL (2.8‐4.4pg/mL), ketonuria, multiple electrolyte deficiencies, acute kidney injury (AKI), and mild transaminitis. Burch‐Warsofsky point score was 40, consistent with impending thyroid storm. We started fluid resuscitation, methimazole 10mg daily and propranolol. On day 4, she had significant clinical improvement with decreasing β‐hCG and thyroid levels. On day 6, TSI, Trab and TPO antibodies resulted negative, thus ruling out Graves' disease. This confirmed our suspicion for GTT and methimazole was stopped. On day 9, β‐hCG: 61,205 mIU/mL (7,512‐132,084mIU/mL at 16‐weeks' gestation), TSH: 0.015 mIU/mL (0.4‐5.3mIU/mL), fT4: 0.76 ng/dL, fT3: 2.9 pg/mL, normal liver and kidney function. She was discharged on day 10 and she was symptom‐free at her 20‐weeks gestation follow‐up.

Discussion: Most common causes of thyrotoxicosis in pregnancy are GTT and Graves disease. GTT has an incidence of 1%‐3% pregnancies. GTT occurs in HG when high levels of hCG bind to the TSH receptor and stimulate thyroxine production. The clinical course of GTT follows the natural curve of hCG levels, peaking at 10‐14 weeks and resolving by 20‐weeks. In our case, AKI also contributed to such high levels of β‐hCG, as 20% of β‐hCG is metabolized by kidney. GTT related thyroid storm is rare, but a short course of thioamides was reasonable given our patient's concerning presentation, unknown autoantibody status, morbidity and mortality associated with untreated thyrotoxicosis of any etiology. Including GTT associated with HG within the differential for thyrotoxicosis in pregnancy is crucial, since it is transient, and treatment is supportive.

POSTER 406

Disorders of Thyroid Function Clinical Poster

TIME‐RESTRICTED EATING WITH OR WITHOUT LOW‐CARBOHYDRATE DIET IMPROVES THYROID FUNCTIONS AND CARDIAC ZYMOGRAMS OF METABOLIC SYNDROME INDIVIDUALS

Yixuan Zheng, Mingqian He*, Bingyin Shi

Department of Endocrinology, the First Affiliated Hospital of Xi'an JiaoTong University, No.277, West Yanta Road, Xi'an, Shaanxi, 710061, P.R. China., China

Objective: Obesity and metabolic syndrome (MetS) have become pressing worldwide health problems, predisposing to cardiovascular disease and also affecting the thyroid axis. Lifestyle intervention, especially dietary intervention, was confirmed as a promising way to weight loss and improve MetS. The present study investigated the effects of diverse dietary interventions on thyroid functions and cardiac zymograms in MetS individuals.

Methods: We conducted a secondary analysis in a randomized clinical trial (NCT04475822). A total of 162 participants with MetS were randomized to receive 3‐month intervention with low‐carbohydrate diet (LCD), 8h time‐restrict eating (TRE), or their combination (Combi). Thyroid functions (T3, T4, FT3, FT4, and TSH), thyroid autoantibodies (TGAb, TMAb, and TPOAb), and cardiac zymograms (LDH, CK, CKMB, HBDH) were tested. We also explored whether the effect differs between early TRE and late TRE groups. Per‐protocol analysis was carried out to verify the reliability of results.

Results: 135 participants accomplished the 3‐month trial and were included in this analysis. As compared to baseline, all 4 cardiac enzymes and FT3 declined, and FT4 elevated in all 3 intervention groups, and T3 decreased only in Combi group. In particular, only TRE and combination treatment significantly improved CK and TGAb after per‐protocol analysis. Early TRE and late TRE showed comparable benefits on FT3 and FT4, and no significant difference was observed among 3 groups in both preliminary and per‐protocol analysis. Moreover, CK, T3 and FT3 were positively associated with visceral fat, CHOl and TG, while FT4 was negatively associated with insulin, C‐peptide and HOMA‐IR at baseline.

Conclusion: The data suggested that thyroid hormones were closely correlated with cardiovascular risk factors. Separate or combined TRE and LCD all altered thyroid hormones, thyroid autoantibodies, and myocardial enzymes in MetS participants, while TRE with or without LCD performed more improvement. In conclusion, an 8h TRE with or without LCD could improve thyroid function and cardiac zymograms for MetS.

POSTER 407

Disorders of Thyroid Function Clinical Poster

REFERENCE INTERVALS FOR TRIGLYCERIDE‐GLUCOSE (TYG) INDEX AND ASSOCIATION BETWEEN TYG INDEX AND THYROID FUNCTION : A CROSS‐SECTIONAL SURVEY IN CHINA

Chenyu Zhang*, Haoyu Wang, Weiping Teng, Zhongyan Shan

China Medical University, China

Objective: Thyroid function is associated with metabolic diseases. Insulin resistance is the common pathological basis of metabolic diseases. Therefore, we explored the relationship between the simple insulin resistance assessment index triglyceride‐glucose (TyG) and thyroid function in the Chinese population.

POSTER 408

Disorders of Thyroid Function Clinical Poster

SARS COV2 ASSOCIATED THYROIDITIS IS NOT LINKED TO WORSE OUTCOMES IN INDIVIDUALS WITH COVID‐19

Anjali Manavalan*^1,2, Hanna Lee^1,2, Xianhong Xie³, Aloke Maity⁴, Yaron Tomer^1,2

¹Department of Medicine, Albert Einstein College of Medicine, USA,²Division of Endocrinology , Montefiore Medical Center, USA,³Division of Epidemiology and Population Health, Albert Einstein College of Medicine, USA,⁴Albert Einstein College of Medicine, USA

Objectives: The objective of our study was to evaluate the spectrum of thyroid function abnormalities associated with COVID‐19 and investigate its association with inflammatory markers, disease severity, and mortality.

Methods: We conducted a retrospective chart review of individuals who were admitted to Montefiore Medical Center between March 2020 and June 2021 with nasal swabs positive for SARS‐CoV2 and low TSH noted during or after the admission. Individuals with known thyroid disease, previously abnormal thyroid function and those using antithyroid drugs or thyroid hormone replacement were excluded. NIH definitions of COVID‐19 severity were utilized to divide subjects into two groups: those with mild disease and those with moderate or severe disease. Thyroid dysfunction was classified as COVID‐associated hyperthyroidism (Low TSH with normal or high T3 and/or T4) or non‐thyroidal illness (Low TSH with low T3 and/or T4).

Results: 140 individuals (44% male, 56% female, 46% Hispanic, 38% Black) meeting study criteria were identified. COVID‐associated hyperthyroidism occurred more frequently in those with mild disease (96% vs 83% p = 0.03) whereas non‐thyroidal illness was associated with moderate or severe disease (17% vs 4% p = 0.03). No association between TSH, T4 or T3 and inflammatory markers was noted. COVID‐associated hyperthyroidism was not associated with mortality.

Discussion: The mechanism of thyroiditis associated with COVID‐19 remains unknown. Our results reveal that the presence of thyroiditis does not correlate with disease severity, levels of inflammatory markers or mortality. Given that inflammatory markers were not associated with hyperthyroidism, cytokines seem less likely to trigger thyroiditis in SARS‐CoV2 infection. We speculate that direct infection with the virus may play a part in the development of thyroiditis, similar to what we have previously shown in the case of HCV. More research is needed to understand the mechanisms of thyroid dysfunction associated with COVID‐19.

POSTER 409

Disorders of Thyroid Function Clinical Poster

THE USE OF ACETAMINOPHEN ABSORPTION TEST IN A PATIENT WITH CONCERN FOR MALABSORPTION OF ORAL LEVOTHYROXINE

Ekta Tirthani*, Van Phan, Jacqueline Kung

Tufts Medical Center, USA

Introduction: In the setting of a national shortage of intravenous (IV) levothyroxine and a high relative cost compared to oral levothyroxine, even patients with suspected malabsorption may be trialed on enteral levothyroxine. Traditionally, test‐loading doses of levothyroxine, up to 1000 mcg at a time, or 7 days' dose of levothyroxine at a time may be given. However, this may not be preferable in critically ill or cardiac patients. The Acetaminophen Absorption Test (AAT) is an alternative method to determine if enteral absorption is adequate.

Case description: A 63‐year‐old female with a history of hypothyroidism and atrial fibrillation (AFib) was admitted to the hospital with autoimmune encephalitis. She was initially started her home dose of 1.6mcg/kg of oral levothyroxine (100 mcg). However, the patient's free T4 levels declined despite the appropriate administration of levothyroxine (spaced apart from continuous tube feeds and other medications). The primary team started IV levothyroxine therapy of 100 mcg every other day with subsequent improvement in her free T4 and TSH. We used the Acetaminophen Absorption Test (AAT) to determine if the patient could be transitioned to enteral levothyroxine. 975mg of oral acetaminophen solution was administered, and a serum acetaminophen level checked 60 minutes later was found to be 8mcg/mL (detectable), indicating sufficient gastrointestinal absorption. Oral levothyroxine was started at 100mcg daily; however, due to down‐trending free T4 levels, the dose was titrated up to 300mcg daily (5mcg/kg), after which free T4 and TSH normalized.

Conclusion: This case highlights that although the results of the AAT can be used as a surrogate marker to rule in or out absolute malabsorption, it cannot be used to determine the degree of malabsorption of drugs like levothyroxine which may have to be given at higher doses in a patient with even a normal result on the AAT.

POSTER 410

History of Thyroid Clinical Poster

THE ROLE OF THE ATA IN PROTECTING THE THYROID FROM THE EFFECTS OF RADIATION

Arthur Schneider*¹, Michael Kaplan²

¹University of Illinois Chicago, USA,²Associated Endocrinologists, USA

The ATA has played an important role in protecting the thyroid from radiation exposure and its attendant risk of thyroid cancer. Starting in the late 1930s external radiation was used to treat benign conditions in the head and neck area. Starting in 1944, I‐131 was released from the Hanford nuclear facility producing plutonium for use in World War II and subsequent international above ground nuclear testing.

1950: Louis Hempelmann begins the first prospective study of radiation‐induced thyroid cancer. In 1968 he published the first dose‐response analysis.

1984: David Becker, et al. “The Use of Iodine as a Blocking Agent in the Event of a Reactor Accident: Report of the Environmental Hazards Committee of the ATA.”

1993: Jenusz Nauman and Jan Wolff publish landmark paper on the safety of KI used in Poland after Chornobyl.

1995: Elaine Ron, et al.: Published definitive “pooled analysis” of seven radiation studies. Cited ∼1,000 times.

2002: ATA, Jacob “Jack” Robbins, and others advocate for the distribution of KI around nuclear power plants. Legislation for stockpiling and distribution in a 20‐mile radius followed.

2008: ATA issues concern when White House reduces radius to 10 miles.

2011: ATA Joins “Image Gently” campaign

2013: “Policy Statement on Thyroid Shielding During Diagnostic Medical and Dental Radiology”

2017: Leung et al.: “ATA scientific Statement on the use of KI Ingestion in a Nuclear Emergency”

Conclusion: Radiation threats to the thyroid continue and the ATA should continue to advocate for measures that reduce or eliminate radiation risks to the thyroid.

POSTER 411

Pediatrics Case Study Poster

RADIOACTIVE IODINE TREATMENT CHALLENGE IN A YOUNG CHILD WITH PAPILLARY THYROID CANCER

Samuel Engle*, Robert Chun, Matthew Plunk

Medical College of Wisconsin, USA

Introduction: In pediatric patients with metastatic papillary thyroid cancer radioactive iodine treatment is often a component of treatment following surgical intervention. This involves swallowing a tablet which poses a unique challenge particularly in younger patients.

Description of Case: A 6‐year female presented with thyroid enlargement and right cervical lymphadenopathy. Fine needle aspiration demonstrated Bethesda VI nodule with cervical metastasis. She underwent total thyroidectomy and right neck dissection and final pathology demonstrated diffuse sclerosing variant papillary thyroid cancer with 20/37 lymph nodes positive. Surgical pathology staging PT2pN1b. She was placed on liothyronine 15 mcg twice daily post operatively as radioactive iodine treatment planned and shorter half life of liothyronine compared to levothyroxine.

She discontinued her liothyronine in preparation for radioactive iodine treatment and after 4 days off therapy her family reported increased irritability and fatigue. Nuclear medicine reached out to family and offered child life specialists to help with pill swallowing as tablets are the only formulation available at our institution but was declined by family. Her I‐123 scan was scheduled 2 weeks after stopping liothyronine and her TSH was 250 u[IU]/ml with a Free T4 of <0.28. Her I‐123 therapy had to be cancelled as she had been taking medication with pudding at home and this is not allowed due to contamination risks. She remained off thyroid hormone replacement therapy while practicing pill swallowing and met with child life two visits to confirm ability to swallow tablet. Her hypothyroidism symptoms made this more challenging. She was able to complete I‐123 and I‐131 therapy but was off therapy for 7 weeks while coordinating. She was then started on levothyroxine with improvement of irritability and fatigue.

Discussion: This case illustrates the need for the health care team to evaluate and document proficiency in pill swallowing prior to radioactive iodine treatment in the pediatric population to prevent delay in care. We have changed our protocol at our institution and now require all children who will require radioactive iodine ablation to meet with child life to demonstrate pill swallowing proficiency

POSTER 412

Pediatrics Clinical Poster

PRELIMINARY EXPERIENCES OF A THYROID MICRORNA AND DNA‐BASED FOR THE DIAGNOSIS AND PROGNOSIS OF PEDIATRIC THYROID NODULES

Marcos dos Santos*¹, Bruno Fredi¹, Isabela Martins¹, Andrei de Oliveira¹, Miriane de Oliveira¹, Bruna Rabelo¹, Nathalia Rodrigues¹, Diego Vilela¹, Bruna Rodrigues¹, Yasmin Couto², Mario Araújo Júnior², Fernanda Vaisman²

¹Onkos Molecular Diagnostics, Brazil,²Brazilian National Cancer Institute (INCA), Brazil

Objective: The risk of malignancy (RoM) in thyroid nodules is higher in the pediatric population when compared to adults, including in the cytology indeterminate categories: 10‐40% vs. 50‐93%. Despite this, molecular testing is still recommended and useful in this population. However, the molecular tests available in Latin America are not yet validated in this population. Therefore, our objective is to evaluate the diagnostic performance of a microRNA and DNA‐based thyroid molecular classifier (mir‐THYpe) in the pediatric population.

Methodology: The initial cohort of this study was composed of FNA slides from 29 thyroid nodules (two Bethesda II, nine Bethesda III, seven Bethesda IV, three Bethesda V and eight Bethesda VI), that were subjected to the mir‐THYpe molecular test, which analyzes microRNA profiling, DNA mutations (BRAF V600E and pTERT C228/250T) and fusions of PAX8/PPRAg, RET/PTC1 and RET/PTC3 by qPCR. The anatomopathological reports of the samples were used as the gold standard for performance evaluation.

Results: Of the 29 samples analyzed, three samples were classified as inconclusive, due to low material available in FNA and failing in quality control parameters of the test. From the remaining 26 samples, 18 were classified as positive for malignancy in the molecular classifier, of which 16 were in fact malignant nodules (88.9%) ‐ papillary thyroid carcinomas and microcarcinomas, including four BRAF positive samples. The two false positives, one sample was a colloid goiter and other an oncocytic cell adenoma. Of the remaining eight samples, were classified as negative for malignancy in the molecular test, of which seven were in fact benign nodules. The only false negative sample was an encapsulated variant papillary thyroid carcinoma. In general, from the 26 valid pediatric samples included in this preliminary study, 23 were correctly classified by the molecular classifier (88.5% of accuracy). One case of RET/PTC1 translocation was detected in this cohort.

Discussion/Conclusion: Although preliminary, the results suggest the technical applicability of the mir‐THYpe molecular classifier in pediatric thyroid nodules. A robust validation is still ongoing, including more samples and aiming to increase benign samples, to better assess the predictive values of this molecular test in the pediatric population.

POSTER 413

Pregnancy and Development Basic

EXPERIMENTAL STUDY ON THE EFFECTS OF MATERNAL THYROTOXICOSIS ON NEURODEVELOPMENT AND COGNITIVE FUNCTION OF OFFSPRING

Yang Shi*, Yushu Li

Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, China

POSTER 414

Pregnancy and Development Case Study Poster

NOT ALWAYS CLEAR‐CUT: A CASE OF GESTATIONAL TRANSIENT THYROTOXICOSIS IN A PREGNANT PATIENT WITH GRAVES' DISEASE

Christopher Pham*¹, Caroline Nguyen²

¹LAC+USC Medical Center, USA,²Keck School of Medicine of USC, USA

The differential for hyperthyroidism in pregnancy includes Graves' Disease (GD) and gestational transient thyrotoxicosis (GTT) which have different implications in management. In this case we present a patient with known history of GD who presents with thyrotoxicosis.

A 29yo female G4P2012 presented with vomiting, diarrhea, and chest pressure for two weeks. Patient reported a new diagnosis of GD on methimazole and was compliant for four months without symptoms, but self‐discontinued one month after menses stopped. Ultrasound revealed a 9‐week pregnancy. TFTs revealed a TSH <0.01 (0.27‐4.20 uIU/ml), TT4 16.0(4.5‐11.7 mcg/dL), FT4 1.75(0.93‐1.70 ng/dL), and FT3 5.5 (2.5‐4.3 pg/dL). TRAb and TSI were pending and hCG was 63,995, with previous history of TRAb 3.57 IU/L (0‐0.9 IU/L) at GD diagnosis. Physical exam was notable for goiter and tachycardia, but no exophthalmos. Due to her previous history of GD and clinical findings of thyrotoxicosis and goiter, patient was initiated on propylthiouracil (PTU). On subsequent clinic visit, TRAB/TSI obtained in ER resulted normal and PTU was discontinued. TSH remained suppressed until 19‐weeks‐gestation. TT4 remained within pregnancy reference range throughout gestation. Patient ultimately underwent C‐section per patient request without fetal or maternal complications.

This is a unique case of thyrotoxicosis secondary to GTT in a pregnant patient with known history of GD off medication. GTT is a condition associated with elevated FT4, FT3, and hCG with normal TRAb. Self‐resolving and not associated with poor outcomes, GTT can present with hyperemesis gravidarum and is thought to be more prevalent in patients with a history of treated GD. GD requires treatment with anti‐thyroid drugs (ATD) that have potential teratogenicity, as untreated GD is associated with worse outcomes for both mother and fetus. TRAb/TSI was critical in determining diagnosis. This case highlights that a history of GD does not exclude GTT. The patient was prevented from being unnecessarily treated with ATD throughout the pregnancy preventing possible fetal hypothyroidism. In patients presenting with hyperthyroidism in pregnancy, TRAb/ TSI should be checked to differentiate between GTT and GD.

POSTER 415

Surgery Translational Poster

APPLICATION OF DEEP LEARNING TO IDENTIFY RECURRENT LARYNGEAL NERVE IN ENDOSCOPIC THYROIDECTOMY: ALGORITHM TRAINING AND EARLY CLINICAL EXPERIENCE

Sen Yang*, Zhihong Wang, Huaijin Zheng, Surong Hua, Quan Liao

Peking Union Medical College Hospital, China

Background: Recurrent laryngeal nerve (RLN) injury remains the one of most serious complications in endoscopic thyroidectomy, which has been widely performed worldwide. Artificial intelligence (AI) has already been applied to medical fields, deep learning acting as a typical model. However, AI in surgery has stagnated mostly in the identification of simple objects with a fixed shape, such as surgical instruments and bone landmarks, lacking related research on important anatomical structures. In this study, a deep learning model based on the convolutional neural network (CNN) was established to achieve the real‐time detection of RLN to improve the safety of thyroidectomy procedures.

Method: Two different surgical scenes were adopted to constitute the modeling basement. Videos of endoscopic thyroidectomy via the chest‐breast approach (ETCB) or endoscopic thyroidectomy via trans‐axillary approach (ETTA) from the General Surgery Department, Peking Union Medical College Hospital (PUMCH), were retrospectively enrolled, dating from February 2020 to August 2021. Clips containing RLN were selected and marked by two professional thyroid surgeons. Training and test sets were randomly divided at the ratio of 5:1 and put into the model for learning and examination. Recall and precision were employed to evaluate the algorithm detection effect. Meanwhile, false negatives and false positives were both analyzed. The oriented bounding box detection was established by adopting a modified YOLOv3 network.

Results: In this study, we analyzed a total of 92 videos comprising 113,690 frames to train and test our oriented bounding box detection model for RLN during endoscopic thyroidectomy. The training set consisted of 75,700 images from 42 ETCB videos and 23,111 images from 37 ETTA videos, while the test set included 9,912 images from 7 ETCB videos and 4,967 images from 6 ETTA videos. At an Intersection over Union (IoU) threshold of 0.1, the recall rates for ETCB and ETTA reached 80.6% and 91.4%, respectively, and their precision rates were 78.4% and 82.6%, respectively, highlighting the excellent performance of the deep‐learning model. The model effectively detected RLN in videos with varying discernibility levels. Furthermore, we showcased a real clinical case to illustrate the model's potential for real‐world integration.

Conclusion: Real‐time detection of RLN can be achieved by the deep‐learning model in endoscopic thyroidectomy, in two different surgical scenes. It progressively illustrates the probability of real‐time AI identification on complex anatomical structures.

POSTER 416

Surgery Case Study

OUR EXPERIENCE OF 200 CASES OF THYROID SURGERY UNDER LOCAL ANAESTHESIA VERSUS GENERAL ANAESTHESIA

Dr.Sambhaji Chintale*

cosmo ent superspeciality hospital and research center, India

Background: Local Anaesthesia is now being accepted universally as a safe alternative to general anaesthesia for thyroid surgery. This study was carried out to compare the outcomes of patients undergoing thyroid surgery under local and general anaesthesia.

Methods: 200 patients who underwent thyroid surgery for benign and malignant diseases under local and general anaesthesia from March 2014 to march 2017 were analysed. Patient characteristics analysed were age, sex, pathology lesion size, operating time, length of stay, cost and post‐operative complications.

Results: Mean lesion sizes were 4.5 cms and 6.5 cms in local and general anaesthesia group respectively. Mean operating time was 50, 5 minutes and 75.5 minutes in local anaesthesia and general anaesthesia group respectively. Mean length of hospital stay was 40 hrs, 25 hours and 75.06 hours in local anaesthesia and general anaesthesia group respectively.

Conclusions: Local anaesthesia is a safe alternative to general anaesthesia for patients undergoing thyroid surgery. Use of local anaesthesia has resulted in a decreased length of stay, cost and means operating time, hence useful in a setup with limited anaesthesia time and increased work load

POSTER 417

Surgery Clinical Poster

THE IMPORTANCE OF COMMUNICATION IN OPERATION FOR SURGICAL TRAINING: SINGLE‐CENTER PROSPECTIVE COHORT STUDY

Hyeonuk HWANG*^1,2, Hyeji Kim¹, Hyeryun Park², Jiye Son², Jinwook Choi², Kyu Eun Lee², Su‐jin Kim²

¹Ewha Womans University Medical Center, Korea, Republic of,²Seoul National University Hospital, Korea, Republic of

Objective: Surgical teams consist of multiple healthcare professionals with different levels of training and expertise. Communication and coordination among team members are crucial in achieving optimal surgical outcomes. However, differences in experience and lack of communication may lead to discrepancies to recognize the surgical findings even though the surgical team participate the same operation. Therefore, this study aimed to investigate the differences of recognition according to trainee's experience (resident of clinical fellow) between the attending surgeon.

Methods: This study was conducted as a prospective cohort study from October 2022 to February 2023. A total of 65 thyroidectomy cases were analyzed. All surgical procedures were performed by one attending surgeon and surgical teams consisting of clinical fellows and residents. All surgical participants recorded the following surgical findings for each case: tumor location and size, degree of tumor invasion, extent of surgery, and preservation of parathyroid gland and nerve. The data were collected by a single researcher who was not involved in the surgical procedures and the accuracy was determined by comparing the recorded findings with those of the attending surgeon.

Results: Finally, a total of 114 records from 65 thyroidectomy cases were analyzed. Of these, 64 (56.1%) records were obtained from clinical fellows, and the remaining of 50 (43.9%) records were obtained from residents. The mean accuracy of the surgical findings was 84.1% for clinical fellows and 78.1% for residents, indicating a statistically significant difference between the two groups (P = 0.011). When comparing each variable of surgical findings, the accuracy of identifying the right and left external branch of superior laryngeal nerve (EBSLN) was significantly higher for clinical fellows compared to residents (87.5% vs 46.0% for right EBSLN, and 85.9% vs 54.0% for left EBSLN; both P < 0.001).

Conclusions: Based on the findings of this prospective cohort study, the accuracy of recognition of surgical findings varied depending on the level of the training of the surgical team. Clinical fellows showed significantly higher accuracy in identifying the external branch of superior laryngeal nerve compared to residents. This highlights the importance of proper education and communication among surgical teams to achieve optimal surgical training.

POSTER 418

Surgery Clinical Poster

COMPLETION THYROIDECTOMY: A SAFE OPTION FOR HIGH VOLUME SURGEONS

Jonathan Staav*¹, Peter Issa², Isabel Riccio¹, Mohammad Hussein¹, Jack Cheng², Brandon Magazine¹, Ali Abdelhady³, Mohamed Shama³, Eman Toraih³, Emad Kandil³

¹Tulane University School of Medicine, USA,²Louisiana State University Health Sciences Center School of Medicine, USA,³Department of Surgery, Tulane University School of Medicine, USA

Background: Regarding risk of complication in patients undergoing completion thyroidectomy (cT), several studies report increased risk compared to total thyroidectomy (TT), while others report a decreased risk. Both scenarios are plausible, with an increased risk in consequence of adhesions from the initial procedure or decreased risk of removing only half the thyroid gland. We set out to compare the rates of complication in patients at our institution undergoing thyroid lobectomy (TL), TT, and cT by a single high‐volume surgeon.

Methods: A single‐institution retrospective cohort study where data was collected on patients undergoing TL, TT, or cT by a high‐volume, fellowship‐trained surgeon. Rates of complication were collected and compared between the three cohorts.

Results: A total of 310 patients grouped into three cohorts, included 100 TL patients, 99 TT patients, and 111 cT patients. Cohorts mirrored patient demographics with respect to age (p = 0.39), race (p = 0.61), and body mass index (p = 0.34). Patients underwent their surgery for different indications, malignancy being more common in the cT cohort (TL: 19% vs. TT: 41.4% vs. cT: 58.6%). Cohorts had similar maximum nodule diameters (TL: 1.5 cm vs. TT: 1.4 cm vs. cT: 1.6 cm, p = 0.39). Overall rate of complication was 4.2%. Rates of complication in the TL, TT, and cT cohorts were 1%, 7.1%, and 4.5%, respectively (p = 0.10). Transient hypocalcemia was slightly more common in the TT cohort (6.1%) as opposed to the TL (0%) or cT (0.9%) patients (p = 0.01). There were no incidences of permanent hypocalcemia or hematoma. The cohorts also had similar rates of recurrent laryngeal nerve loss of signal leading to transient dysphonia (TL: 0% vs. TT: 1% vs. cT: 3.6%, p = 0.10). There were no incidences of permanent recurrent laryngeal nerve injury.

Conclusion: While rates of complication tended to predictably decrease as approaches became less extensive, there were no significant differences in complication rates among the three surgical approaches when performed by a high‐volume surgeon. In specific, cT is a very safe option for patients when performed by a high‐volume surgeon. Considering the low rates of complication overall, patient counseling and preference should be emphasized to provide appropriate and tailored treatment plans.

POSTER 419

Surgery Clinical Poster

COMPLETED THYROIDECTOMY: ROBOTIC ASSISTANCE IS A SAFE AND EFFECTIVE APPROACH

Jessan Jishu*¹, Julia Griffin¹, Bethany Norwood¹, Mohamed Hussein¹, Peter Issa², Xinyi Luo¹, Alyssa Webster¹, Manal Malik¹, Nicke Worth¹, Ali Abdelhady¹, Mohamed Shama¹, Eman Toraih¹, Emad Kandil¹

¹Tulane University School of Medicine, USA,²Louisiana State University Health Sciences Center School of Medicine, USA

Objective: Robotic surgery has largely been demonstrated as a safe and effective approach for thyroid surgery, including standard procedures such as a hemithyroidectomy and total thyroidectomy. Limited research has been conducted to investigate the use of robotics in completion thyroidectomy procedures. This study aims to compare surgical outcomes of patients undergoing completion thyroidectomy by the conventional approach to those undergoing robotic‐assisted completion thyroidectomy.

Methods: We performed a single‐institution prospectively‐collected cohort study including 131 patients who underwent completion thyroidectomy. Surgical approaches included either an open conventional approach or a robotic‐assisted remote access (36 trans‐axillary, 8 retro‐auricular) approach.

Results: Patients were sub‐grouped into two cohorts, of which 87 (66.4%) underwent conventional completion thyroidectomy and 44 (33.6%) underwent robotic‐assisted completion thyroidectomy. The overall rates of complication were similar in the robotic‐assisted (9.1%, N = 4) and conventional (6.9%, N = 6) cohorts (p = 0.73). The rate of postoperative transient dysphonia due to recurrent laryngeal nerve signal loss in the whole patient population was 4.6% (N = 6 patients) and similar between the two cohorts (p = 0.66), though it tended to be lower in the robotic‐assisted cohort (2.3%, N = 1 vs. 5.7%, N = 5). Patients undergoing robotic‐assisted completion thyroidectomy had longer total operative times (139 minutes vs. 99 minutes, p < 0.001). Operative time remained significantly longer in the robotic surgery cohort even following stratification by post‐operative malignancy status (benign: 106 minutes vs. 132.5 minutes, p = 0.016; malignant: 99 minutes vs. 143.5 minutes, p = 0.007). The cohorts had similar amounts of intraoperative blood loss (p = 0.44). The robotic surgery cohort however had shorter lengths of stay (p = 0.006), with a considerable population undergoing same‐day discharge (25.0% vs. 5.7%).

Conclusion: Robotic‐assisted completion thyroidectomy had similar rates of complications and blood loss in comparison to the conventional thyroidectomy surgical approach. The robotic assisted approach did, however, result in shorter lengths of hospitalization in comparison to the conventional surgical approach. Robotic‐assisted completion thyroidectomy is a safe and effective surgical approach for patients requiring surgery. Further studies with a larger patient population are warranted to expand on these findings and allow sub‐group analysis, including comparison of the trans‐axillary versus the retro‐auricular procedural approaches.

POSTER 420

Surgery Clinical

COMPARISION BETWEEN IMMEDIATE VS DELAYED BLEEDING AFTER THYROIDECTOMY

Jun Sung Lee*, Jin Seok Lee, Hyeok Jun Yun, Hojin Chang, Seok‐Mo Kim, Yong Sang Lee, Hang‐Seok Chang

Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Korea, Republic of

Background: It is important to identify risk factors for post‐thyroidectomy bleeding that requires airway intervention or surgery . In this study, we divide the bleeding cases into two groups, immediate and delayed, and investigate whether there was a difference in each group.

Methods: From March 2009 to June 2022, we retrospectively compared 126 post‐thyroidecotmy bleeding cases into three groups according to the period between the thyroidectomy and reoperation due to bleeding(1day, 1 ∼ 7days, 7days∼). We investigated patient characteristics, surgical procedure kinds, and clinical outcomes.

Results: There was a significance difference in male‐female ratio in three group. The ratio of male was increased as re‐op period became longer. There was a definite distinction in the ratio of total thyroidectomy and lateral neck dissection. As the re‐op period became longer, the ratio of total thyroidectomy and lateral neck dissection was increased. The operation time also showed difference among groups.

Conclusions: In the comparison of bleeding according to period from thyroidectomy to reoperation due to bleeding, there was a difference of ratio in some parameter such as male, total thyroidectomy, and lateral neck dissection. As the re‐op period became longer, there parameter's ratio was larger.

POSTER 421

WITHDRAWN

POSTER 422

Thyroid Cancer Basic Poster

EFFECTS AND MECHANISMS OF TRANSCRIPTION FACTOR BNC1 ON PROLIFERATION, MIGRATION, INVASION AND EPITHELIAL–MESENCHYMAL TRANSITION IN PAPILLARY THYROID CANCER

YANSHI YE, Huixian Zeng, Yaosheng Luo, Jie Shen*

The First People's Hospital of Shunde, China

Introduction: Cancer cells become more aggressive through epithelial‐mesenchymal transition (EMT). Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, and its incidence has increased significantly in recent decades. It has been reported that EMT promote the progression of PTC to poorly differentiated thyroid cancer (PDTC). Objective: This study aims to discover the characteristics and the molecular mechanism of EMT in PTC cell.

Methods: We found that BNC1 is a key transcription factor in EMT cancer cell by single‐cell RNA sequencing (scRNA‐seq). Then, we analyzed the relationship between BNC1 expression levels and clinicopathological features of thyroid cancer (TCGA database). Next, we adopted EdU incorporation assay, scratch healing and transwell invasion experiment to detect the effect of BNC1 on the proliferation, migration and invasion in TPC‐1 cells. We also measured the expression of EMT related genes, ARID5B and p‐AKT.

Results: It showed that the expression of BNC1 in thyroid cancer was upregulated, and high expression of BNC1 was associated with higher T stage, lymph node metastasis, extra‐thyroid invasion and histologic type. We found that suppressing the expression of BNC1 inhibited the proliferation, migration, invasion and EMT in TPC‐1 cells. Knocking down BNC1 down‐regulates the expression of ARID5B and p‐AKT levels. Overexpressing ARID5B reverse BNC1‐induced changes. What is more, luciferase reporter assay shows that BNC1 promotes ARID5B expression by interacting with its promoter region.

Conclusion: BNC1 is a marker of EMT PTC cells and is associated with T stage, lymph node metastasis, extra‐thyroid invasion, and histologic type of thyroid cancer. BNC1 promotes the proliferation, migration, invasion and EMT of TPC‐1 cells via the ARID5B/AKT pathway.

POSTER 423

Thyroid Cancer Basic Poster

IDENTIFY GHR AS A KEY GENE BY INTEGRATED BIOINFORMATICS ANALYSIS IN THYROID CARCINOMA

Meng Jia*¹, Ye Qin¹, Jiawen Liang¹, Qianqian Li¹, Jianwei Wang², Xiubo Lu¹

¹The First Affiliated Hospital of Zhengzhou University, China,²Zhengzhou University, China

Objective: Thyroid carcinoma (TC) is a common endocrine malignancy with an increasing incidence. Despite there are advances in examination and treatment of thyroid carcinoma, the 5‐year survival rate in advanced patients being only 59%. Therefore, the aim of our study is to identify the potential biomarkers and therapeutic targets of TC.

Methods: We combined four GEO datasets and TCGA dataset, and obtained collective 66 DEGs through differential analysis. The PPI network was constructed by using the STRING, and we screened out the top 10 hub genes from the entire network, including CCND1, CDH2, DCN, CRYAB, ANK2, MAFB, GHR, MYOC, NRCAM and FABP4. We found that GHR had achieved excellent results in survival prognostic prediction. Next, we analyzed GHR‐related functions and performed the immune infiltration analysis of GHR.

Results: We found that GHR has a promising result in predicting survival prognosis. Furthermore, GHR is closely related to thyroid hormone synthesis, immune cells and immune modulator genes.

Conclusion: GHR may affect the progression of TC by affecting thyroid hormone synthesis and T & NK cells levels in TC. Taken together, GHR is a reliable potential biomarker and therapeutic target for TC.

POSTER 424

Thyroid Cancer Basic Poster

LIPOCALIN 2(LCN2) REGULATES PROLIFERATION AND MIGRATION IN PAPILLARY THYROID CARCINOMA CELLS

Huixian Zeng^1,2, Jie Yao³, Jie Shen*²

¹Department of Endocrinology, Affiliated Foshan Hospital,Southern Medical University(Foshan Second People's Hospital), China,²Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), China,³Department of Clinical Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), China

Objective: Recurrence and metastasis remain major challenges in thyroid papillary carcinoma (PTC) diagnosis and treatment. There is a shortage of specific diagnostic markers for PTC, and therapeutic targets are limited. High throughput Single‐cell RNA sequencing (scRNA‐seq) has emerged as a powerful tool for exploring cellular heterogeneity to find novel biomarkers among human cancers.

Methods: Tissue samples from one PTC patient, including paired primary tumor (Ca) and paracancerous tissue (PCa), were subjected to scRNA‐seq with 10 × Genomics. The TCGA databases was chosen for bioinformatics analysis. The expression of LCN2 in PTC tissues and PTC cell lines was detected by immunohistochemistry (IHC) and quantitative real‐time PCR (qRT‐PCR). Loss‐of‐function experiments were performed in vitro to evaluate the effects of LCN2 on the biological behaviors of PTC cells.

Results: The transcriptomes of 29,998 single cells were profiled, and cell landscapes of PTC were composed of malignant epithelial cells, fibroblasts, vascular endothelial cells, T/natural killer cells, myeloid cells, and mast cells. Specifically, we uncovered a malignant epithelial subpopulation characterized by upregulation of Lipocalin 2(LCN2). The expression of LCN2 in tumor tissue was increased in the BRAFV600E mutant patients with PTC compared with in the BRAFV600E wild‐type patients with PTC by exploring TCGA databases. LCN2 expression was up‐regulated in tumor tissues with lymph node metastasis compared with that without lymph node metastasis. Knockdown of LCN2 can significantly attenuate the proliferation, invasion, and migration phenotype of thyroid cancer cells in vitro. Furthermore, the expressions of cell cycle regulatory proteins cyclin D1 and p21 were decreased. Compared with the knockdown of LCN2 group, the expression levels of p‐AKT, p‐GSK‐3βand Cyclin D1 were increased in the knockdown of LCN2 group treated with AKT agonist SC79. Compared with the knockdown of LCN2 group, the proliferation in the knockdown of LCN2 group treated with AKT agonist SC79 was significantly increased, while the cell cycle arrest was significantly decreased.

Conclusion: Our study demonstrated that LCN2 is exclusively expressed in the malignant cells of primary PTC and is closely related to the lymph node metastasis of PTC.LCN2 can promote the proliferation, invasion, and migration of thyroid cancer cells by regulating the cell cycle through AKT/GSK‐3β/Cyclin D1 signal pathway. LCN2 may be a new target for the treatment of papillary thyroid carcinoma.

POSTER 425

Thyroid Cancer Basic Poster

INVESTIGATION OF POLYMORPHIC SELECTIN VARIANTS REVEAL NEW POTENTIAL THYROID CANCER BIOMARKERS

Larissa Rabi^1,2,3, Davi Valente², Karina Peres^1,4, Elisangela Teixeira¹, Natassia Bufalo^1,4,5, Laura Ward*¹

¹Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences, University of Campinas (UNI‐CAMP), Brazil,²Department of Biomedicine, Nossa Senhora do Patrocínio University Center (CEUNSP), Brazil,³Institute of Health Sciences, Brazil,⁴Department of Medicine, Max Planck University Center, Brazil,⁵Department of Medicine, São Leopoldo Mandic and Research Center, Brazil

Selectins are responsible for the early stages of cell migration as they control cell adhesion. They make the microenvironment permissive for metastatic events by promoting the activation of other cell adhesion molecules. We previously demonstrated that among some cell adhesion molecules investigated in 275 patients, including 102 benign and 173 malignant nodules (143 papillary thyroid carcinoma and 30 follicular thyroid carcinoma, L‐selectin expression was able to sort out malignant nodules both using mRNA (p = 0.0027) and protein (p = 0.0020 for nuclear expression). Some selectins like L‐selectin (encoded by the SELL gene), P‐selectin (SELP), E‐selectin (SELE), and PSGL‐1 (SELPLG) have been associated with various types of cancers, more aggressive tumors and poorer prognosis, but their role in thyroid malignancy is still unclear. In order to search for potential biomarkers of thyroid cancer, we aimed to understand the alterations caused by the presence of polymorphisms in the DNA structure of these genes and the consequent alterations in the morphology and function of the corresponding proteins. We employed several robust bioinformatics tools to evaluate gene sequence; single nucleotide polymorphisms (SNPs) in intronic and UTR regions; and missense SNPs with amino acid change in L‐selectin (SELL), E‐selectin (SELE), P‐selectin (SELP) and PSGL‐1 (SELPLG). The non‐synonymous SNPs were retrieved from dbSNP of NCBI (https://www.ncbi.nlm.nih.gov/snp/). The selection was performed considering a minor allele frequency (MAF) between 0.1 and 1.0 in order to select variants that could have a good probability of being validated in patient cohorts. We demonstrated that gene polymorphisms rs2229569, rs1131498, rs4987360, rs4987301 and rs2205849 of SELL gene; polymorphisms rs3917777, rs2205894 and rs2205893 of SELP gene; rs7138370, rs7300972 and rs2228315 variants of SELPLG gene; and rs1534904 and rs5368 polymorphisms of SELE gene may produce important alterations in the DNA structure and consequent alterations in the morphology and function of the corresponding proteins. These selectin polymorphic variants that present relevant minor allele frequency in the population deserve further investigation in thyroid nodule patients, as they may become useful clinical markers for risk determination, diagnostic and prognostic tumor biomarkers, or even targets for targeted cancer therapies.

POSTER 426

Thyroid Cancer Basic Poster

SINGLE‐CELL RNA SEQUENCING REVEALS THE DEDIFFERENTIATION PROCESS OF THYROID CANCER

Zheng Peng*

Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., China

Objective: To analyze the dedifferentiation process of papillary thyroid cancer (PTC) into anaplastic thyroid cancer (ATC) and explore potential targets for intervening in dedifferentiation.

Methods: Multiple single‐cell RNA sequencing datasets of thyroid tissues, including normal thyroid, PTC, and ATC, were integrated. Clustering analysis was performed on the normal epithelial cells and cancer cells of all patients.

Results: There is a gradual dedifferentiation axis from normal thyroid tissue to PTC to ATC. As thyroid epithelial cells gradually dedifferentiated, the expression of TG, TSHR, TPO, PAX8, and HHEX decreased. Some PTC cells are not capable of dedifferentiating into ATC and instead maintain a high level of differentiation. These cells are highly enriched in immune‐related features, such as response to interferon, regulation of innate immune response, and T cell‐mediated cytotoxicity.

Conclusion: The sensitivity to immune killing may prevent PTC from dedifferentiation into ATC.

POSTER 427

Thyroid Cancer Basic Poster

DDB2 AS AN ONCOGENIC BIOMARKER PROMOTES PAPILLARY THYROID CANCER GROWTH AND METASTASIS

Bo Song*

China Medical University, China

Objective: Papillary Thyroid cancer (PTC) is the most common endocrine malignancy worldwide. The incidence of PTC is high and increasing worldwide due to continuous improvements in diagnostic technology. Therefore, determining accurate prognostic predictions to stratify PTC patients is important.

Methods: We analyzed damage specific DNA binding protein 2 (DDB2) expression and its relation with the clinicopathological features of PTC using The Cancer Genome Atlas (TCGA) database. Next, qRT‐PCR analysis and Western blot analysis were used to investigate the expression of DDB2 in PTC tissues and cell lines. Moreover, we investigated the effects of DDB2 knockdown on cell proliferation, apoptosis, metastasis and invasion . Subsequently, a PPI network highly related to the DDB2 encoded protein was constructed using STRING database. The univariate, multivariate, and LASSO Cox regression analyses were used to obtain an DDB2‐Related Gene Risk Signature. We evaluated the signature in terms of prognostic independence, predictive value, immune cell infiltration, immune status and ICI‐related molecules efficacy.

Results: In this study, we found that DDB2 was significantly overexpressed in the TCGA cohort. High expression of DDB2 is associated with worse overall survival (OS), higher grade, node metastasis, and advanced clinical stage in patients with TC. RT‐PCR and Western blot analysis found that DDB2 was unregulated in human PTC tissues and cell lines. Furthermore, DDB2 knockdown significantly suppressed the proliferation, migration, and invasion of TPC cells, and the significantly promoted cell apoptosis. Then we identified 4 DDB2‐related genes as the risk signature, which divided TC patients from the TCGA cohort into two different risk groups. The high‐risk group had a significantly poorerprognosis than the low‐risk group. With the ESTIMATE algorithm, we found that high‐risk group might be associated with the immunosuppressive microenvironment. Several immune checkpoint inhibitor (ICI)‐related molecules, such asPD‐1 and PD‐L1, showed a positive correlation with the high‐risk group.

Conclusion: Our findings indicated that DDB2 might be involved in the progression of TC and can be used as a potential therapeutic target. Moreover, we constructed a DDB2‐related risk signature that can predict TC patient survival, and also sheds light on TC's novel clinical treatments, such as ICB therapy.

POSTER 428

Thyroid Cancer Basic Poster

LONG‐TERM EXPOSURE TO DECABROMODIPHENYL ETHER INDUCES ACQUIRED DABRAFENIB RESISTANCE IN BRAF MUTATED THYROID CANCER THROUGH MAPK SIGNAL WAY

Zhiyan Liu*

Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China

Objective: As an analogue of thyroid hormone, Decabromodiphenyl ether (BDE209) was found to have tumorigenic effects on the thyroid carcinoma. For advanced thyroid carcinoma patients harboring BRAFV600E mutation, BRAF kinase inhibitor Dabrafenib has dramatically changed the therapeutic landscape, but drug resistance often leads to termination of the single agent treatment.

POSTER 429

Thyroid Cancer Translational Poster

Β‐CATENIN ATTENUATION LEADS TO UP‐REGULATION OF ACTIVATING NKG2D LIGANDS AND TUMOR REGRESSION IN BRAFV600E‐DRIVEN THYROID CANCER CELLS

Minjing Zou*, Suhad Al‐Yahya, Monther Al‐Alwan, Huda BinEssa, Khalid Abu Khabar, Falah Almohanna, Abdullah Assiri, Abdulmohsen Altaweel, Amal Qattan, Brian Meyer, Ali Alzahrani, Yufei Shi

King Faisal Specialist Hospital and Research Centre, Saudi Arabia

BRAFV600E mutations frequently occur in papillary thyroid cancer (PTC). β‐catenin, encoded by CTNNB1, is a key downstream component of the canonical Wnt signaling pathway and is often overexpressed in PTC. BRAFV600E‐driven PTC tumors rely on Wnt/β‐catenin signaling to sustain growth and progression. In the present study, we investigated the tumorigenicity of thyroid cancer cells derived from BrafV600E PTC mice following Ctnnb1 ablation (BVE‐Ctnnb1^null). Remarkably, the tumorigenic potential of BVE‐Ctnnb1^null tumor cells was lost in nude mice. Global gene expression analysis of BVE‐Ctnnb1^null tumor cells showed up‐regulation of NKG2D receptor activating ligands (H60a, H60b, H60c, Raet1a, Raet1b, Raet1c, Raet1d, Raet1e, and Ulbp1) and down‐regulation of inhibitory MHC class I molecules H‐2L and H‐2K2 in BVE‐Ctnnb1^null tumor cells. In vitro cytotoxicity assay demonstrated that BVE‐Ctnnb1^wt tumor cells were resistant to NK cell‐mediated cytotoxicity, whereas BVE‐Ctnnb1^null tumor cells were sensitive to NK cell‐mediated killing. Furthermore, overexpression of any one of these NKG2D ligands in the BVE‐Ctnnb1^wt cell line resulted in a significant reduction of tumor growth in nude mice. Our results indicate that active β‐catenin signaling inhibits NK cell‐mediated immune responses against thyroid cancer cells. Targeting the β‐catenin signaling pathway may have significant therapeutic benefits against thyroid cancer by not only inhibiting tumor growth but also enhancing host immune response.

POSTER 430

Thyroid Cancer Translational Poster

THE DEVELOPMENT OF THE FIRST CROSS‐POPULATION MICROSIMULATION MODEL TO REPRESENT PAPILLARY THYROID CARCINOMA EPIDEMIOLOGY IN THE UNITED STATES

Oguzhan Alagoz*¹, Yichi Zhang¹, Natalia Arroyo¹, Sara Fernandes‐Taylor¹, Dou‐Yan Yang¹, Manasa Venkatesh¹, Vivian Hsiao¹, Erin Bowles², Louise Davies^3,4,5, David Francis¹

¹University of Wisconsin‐Madison, USA,²Kaiser Permanente Washington, USA,³The VA Outcomes Group, Department of Veterans Affairs Medical Center College, USA,⁴Geisel School of Medicine at Dartmouth, USA,⁵The Dartmouth Institute for Health Policy and Clinical Practice, USA

Objective: Evidence‐based thyroid cancer control requires answering open questions, such as optimal biopsy recommendations and utility of active surveillance. Prospective trials and conventional statistical models are not always feasible to address such open questions. We developed the PApillary Thyroid CArcinoma Microsimulation model (PATCAM; NIH R01 2020‐2025). PATCAM replicates thyroid cancer epidemiology in the U.S. over time using a modeling approach that has been successfully applied to address similar questions for breast, lung, and colon cancer and informed guideline development by US Preventive Services Task Forces and American Cancer Society. To date, no similar microsimulation model has been developed for thyroid cancer.

Methods: PATCAM simulates individuals by birth cohort from age 15 until death starting from 1975 using five inter‐related components: (1) natural history; (2) detection: representing the use and effectiveness of ultrasound and biopsy; (3) healthcare utilization/referral; (4) treatment; and (5) other‐cause mortality. PATCAM was developed using high‐quality data including age and sex‐specific thyroid ultrasound referral and biopsy rates between 1993 and 2015. Parameters governing the natural history of thyroid cancer were estimated using a novel machine learning‐based calibration procedure and the CONDOR high‐throughout computing system.

Results: PATCAM successfully replicates observed age‐, sex‐, and stage‐specific incidence and mortality as reported by the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2015 indicating internal validity. In particular, PATCAM mimicked the drastic increase in thyroid cancer incidence between 1990s and 2010 as well as flattening of incidence since 2010. Predicted age‐adjusted overall incidence fell within 99% confidence intervals of reported data in 32 and 35 out of 41 years for females and males, respectively. Predicted sex‐ and age group‐specific incidence as well as predicted mortality fell within the 95% confidence intervals of the reported data in most years.

Discussion: PATCAM is the first simulation model that successfully reproduces observed US thyroid cancer incidence including sex‐ and age‐specific differences in thyroid cancer trends. PATCAM is poised to address counterfactual problems (e.g., impact of incidental imaging on thyroid cancer incidence, optimal biopsy timing, and utility of active surveillance) within thyroid cancer that cannot be answered with conventional statistical models.

POSTER 432

Thyroid Cancer Translational Poster

ASSOCIATION BETWEEN HIGH EXPOSURE TO PER‐ AND POLYFLUOROALKYL SUBSTANCES (PFAS) EXPOSURE AND THYROID CANCER RISK

Maaike van Gerwen*¹, Elena Colicino¹, Haibin Guan¹, Georgia Dolios¹, Mathilda Alsen¹, Girish Nadkarni¹, Eric Genden¹, Lauren Petrick^1,2

¹Icahn School of Medicine at Mount Sinai, USA,²The Bert Strassburger Metabolic Center, Sheba Medical Center, Israel

Objective: Exposure to per‐ and polyfluoroalkyl substances (PFAS) is a potential contributor to the increasing thyroid cancer trend. Therefore, the current study investigated whether high levels of individual PFAS are associated with an increased risk of thyroid cancer diagnosis.

Methods: A nested case‐control study was performed using 31 thyroid cancer patients with plasma samples collected ≥1 year before cancer diagnosis and 31 pair‐matched healthy (non‐cancer) controls available in BioMe, a medical record‐linked biobank at the Icahn School of Medicine at Mount Sinai in New York. Since 2007, BioMe has been collecting plasma samples, clinical medical record and questionnaire data of study participants from all New York City (NYC) boroughs and the larger metropolitan area, thus representing a diverse racial/ethnic and socioeconomic population. We measured eight PFAS chemicals using untargeted liquid chromatography‐ high resolution mass spectrometry. For each PFAS, participants were characterized as high or low PFAS exposure by the median PFAS intensity. We then calculated hazard ratios (HR) from a Cox proportional‐hazards model to investigate the association between cancer and high and low PFAS exposure, adjusting for age, sex, race, BMI, and storage time.

Results: The mean time between plasma sample collection and thyroid cancer diagnosis was 4 years. The HR for the cancer‐PFAS association was significantly different for the following PFAS: linear perfluorohexanesulfonic acid (HR: 1.6 (95% CI: 1‐2.7); p: 0.049) and branched Perfluorooctanesulfonic acid (HR: 1.4 (95% CI: 1‐.1); p: 0.043). A tendency towards significance was found for perfluorooctylphosphonic acid (HR: 1.4 (95% C: 0.99‐1.9); p: 0.059)).

Discussion/ Conclusion: PFAS chemical exposure is associated with harmful effects, including thyroid dysfunction and carcinogenesis. To our knowledge, this is the first prospective study to examine the association between high PFAS exposure and thyroid cancer risk. Results of our study provide critical evidence that high PFAS exposure increases thyroid cancer risk thus warranting the reduction of PFAS from potential exposure routes (e.g., drinking water, water‐resistant clothing, plastic packaging, etc.).

POSTER 433

Thyroid Cancer Translational Poster

RASOPATHIES UNLEASHED: DECODING THE DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE IN THYROID NODULES

Eman Toraih*¹, Emad Kandil²

¹Tulane, USA,²Tulane, USA

Objective: RAS mutations are among the most frequently identified genetic alterations in thyroid nodules, and their presence has been associated with a higher risk of malignancy. Human Genome Epidemiology (HuGE) analysis will enhance our understanding of these complex driving mutations and their impact on thyroid health. We aimed to decipher the diagnostic and prognostic implications of various types of Ras mutations on risk of malignancy and metastasis.

Method: Genetic variants of NRAS, KRAS, and HRAS in various thyroid diseases were investigated in several databases and literature, including COSMIC database, Multi‐cancer AACR project GENIE registry, cBioPortal for Cancer Genomics, and Genomic Data Commons Data Portal. In addition, RAS mutations at codons 12, 13, and 61 were analyzed in 470 thyroid cancer patients of our institute. The prevalence of RAS mutations was compared across age, sex, race, pathological subtypes, nodal infiltration, distant metastasis, recurrence, and iodine intake. Regression analyses were employed to assess prognostic implications of RAS‐associated thyroid neoplasms.

Results: The study examined 2917 indeterminate, 6449 benign, and 38545 malignant nodules in patients with adenoma/goiter and different types of thyroid cancer, including papillary, follicular, anaplastic, medullary, insular, and Hurthle cell TC. The prevalence of NRAS was higher in malignant than benign nodules in the Black population (p = 0.007) and poorly differentiated TC (PDTC) (p = 0.001). Nodules with NRAS Q61 mutations were more likely to be malignant (RR = 1.07, 95%CI = 1.05‐1.08, p < 0.001). Patients with NRAS mutations were less likely to have nodal metastasis (p < 0.001) and extrathyroidal extension (p = 0.006), and exhibited higher survival times in the presence of TERT and BRAF mutations. However, Q61K was associated with distant metastasis in PDTC (p = 0.033).

Conclusion: Our results showed that genetic alterations of RAS genes have different impact on patient's outcomes. Therefore, it is crucial to evaluate these mutations while considering the patient's overall clinical situation.

POSTER 434

Thyroid Cancer Case Study Poster

ABERRANT KI‐67 IMMUNOREACTIVITY OF A HYALINIZING TRABECULAR TUMOR IN MULTINODULAR THYROID GOITER: REVISITING THE HALLMARKS OF THIS UNIQUE THYROID NEOPLASM

Arya May*, Anitha Gondhi, Mouna Gunda, Carlos Arguello

University of Alabama Birmingham, USA

Introduction: Hyalinizing trabecular tumor (HTT), per the 2022 WHO classification, is a low‐risk follicular cell‐derived neoplasm with a prevalence of <1% of thyroid neoplasms. While histology overlaps with medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC), HTT has a distinctive immunohistochemical profile. We present a case of HTT with unique immunohistochemistry characteristics.

Description of the Case: A 65‐year‐old female presented for evaluation of a multinodular goiter (MNG) discovered incidentally during dysphagia evaluation. She had no other compressive symptoms. She denied any history of neck irradiation, and no personal or family history of cancer. She was clinically euthyroid, confirmed by normal thyroid function tests. Thyroid ultrasonography revealed two hypoechoic nodules in the right lobe, three sub‐centimeter nodules in the left lobe, and one isthmus nodule measuring 2.1 cm x 1.9 cm. FNA of the largest nodules in both lobes and isthmus was performed. FNA cytology revealed MTC in the isthmic nodule. Serum calcium, calcitonin and plasma free metanephrines were within the normal reference range. Neck CT revealed concerning cervical lymph nodes.

She underwent total thyroidectomy with central compartment lymphadenectomy. Cytopathology showed nodular thyroid hyperplasia with hyalinizing trabecular isthmus tumor without metastasis, infiltration, or invasion. Histological examination of the isthmus tumor showed prominent trabeculae architecture with abundant intertrabecular and focal intra‐trabecular hyaline, psammoma bodies, negative CK19, and calcitonin immunostaining‐ classic for HTT. The tumor immunoreactivity was negative for call membrane staining for Ki‐67. Nonetheless, HTT was confirmed based on the immunohistochemical profile despite <1% Ki‐67 proliferation of the cell membrane: a distinctive feature of HTT but lacks sensitivity. Serial neck imaging of our patient over the eight years post‐surgery shows no evidence of recurrence.

Discussion: Immunostaining and histopathology of a resected tumor helps identify HTT. Ki‐67, a clone of MIB‐1, is membranous staining that helps differentiate HTT from PTC or other malignant thyroid tumors. An accurate diagnosis of HTT is crucial to avoid overtreatment of this indolent tumor since conservative surgical excision is the mainstay treatment of HTT. The absence of Ki‐67 makes this case unique and provides an opportunity to revisit the histology and immunoreactivity of HTT.

POSTER 435

Thyroid Cancer Case Study Poster

METASTATIC DIFFERENTIATED THYROID CANCER WITH NEGATIVE THYROGLOBULIN AND THYROGLOBULIN ANTIBODY: A CASE REPORT

Ibrahim Ajwah*, Lujain Alkhalifa, Sameerah Alshehri

Department of Endocrinology, Diabetes and Metabolism, King Abdulaziz Medical City, Ministry of the National Guard‐Health Affairs, Saudi Arabia

Introduction: Thyroglobulin (Tg) has been established as a reliable tumor marker in patients with differentiated thyroid cancer (DTC). Thyroglobulin can be measured in non‐stimulated stat while the patient is on the levothyroxine replacement therapy or in stimulated stat after levothyroxine withdrawal or through the use of human recombinant TSH. Long‐term measurement of the Tg and Tg antibodies (TgAB) levels as a routine surveillance plays a valuable role in predicting the presence of tumor residual or recurrence. While some patients will have an incomplete biochemical response after the initial therapy (elevated Tg/ TgAB) with negative structural imaging, including the whole‐body radioiodine scan (WBS) assessment, the opposite is rarely encountered. We report a case of iodine avid metastatic differentiated thyroid cancer (DTC) with undetectable Tg levels and negative TgAB.

Description of the Case: A 53‐year‐old lady who initially presented spinal cord compression from a spinal lesion which turned out to be a metastatic DTC. Subsequently, she underwent a total thyroidectomy with central neck dissection. Histopathological examination confirms a unifocal 3.5 cm, left thyroid lobe, widely invasive follicular carcinoma. The post‐operative biochemical assessment reveals undetectable stimulated Tg level along with negative TgAB. While the WBS shows multiple foci of radiotracer activity involving the thyroid bed, cervical spine, sacrum, and bilateral lungs. Tg levels remain undetectable despite a serial measurement and Tg dilution to rule out both laboratory error and the Hock effect. Additionally, she was treated with a therapeutic dose of radioactive iodine ablation and palliative radiotherapy to the cervical spine.

Discussion: Long‐term monitoring of Tg/TgAB along with structural imaging is the standard for monitoring patients with DTC. Although low or undetectable Tg/TgAB levels during the postoperative period are good prognostic indicators, it should not replace structural imaging, especially in a high‐risk DTC group.

POSTER 436

Thyroid Cancer Case Study Poster

SUBLINGUAL PAPILLARY THYROID CANCER: A CASE REPORT

Lisette Rodriguez*, Christine Eagleson

University of Virginia, USA

Introduction: Ectopic thyroid tissue is a rare entity that results from incomplete migration of the thyroid gland during embryogenesis. Thyroid carcinomas arising from ectopic thyroid tissue are unusual and can represent a therapeutic challenge because, due to the rarity of this entity, there is no consensus about the optimal treatment strategy.

Case Report: A 47‐year‐old female presented to the clinic with a left neck mass. Neck ultrasound showed a heterogeneous, an abnormal level III lymph node measuring 8 x 9 x 9 mm. In addition, multiple thyroid nodules were identified, including a dominant left lower lobe nodule measuring 1.5 x 1.8 cm, and a mid‐right thyroid nodule measuring 1.3 x 1.4 cm. FNA biopsy of these lesions showed follicular lesion (left nodule), papillary thyroid carcinoma (right nodule), and rare atypical cells (lymph node). She underwent total thyroidectomy and left neck lymph node dissection. Surgical pathology reported multifocal, bilateral papillary thyroid cancer with greatest dimension of 2 cm, and one level III lymph node positive for papillary thyroid cancer. She underwent radioactive iodine therapy (151.3 mCi). Post‐RAI scan showed bilateral uptake in thyroid bed consistent with residual thyroid tissue, and no evidence of metastatic disease. Her thyroglobulin nadired at 11 and then continued to rise in subsequent months. She had a neck ultrasound which showed an 8mm hypoechoic lesion in the right thyroid bed. A CT neck showed a 1.7 x 2.5 x 2 cm midline sublingual space mass suspicious for ectopic thyroid tissue. She underwent FNA biopsy of this tissue which confirmed papillary thyroid carcinoma. She underwent external beam radiation therapy to the base of the tongue (70 Gy in 35 fractions). 6‐months post‐radiation therapy, she had a PET‐CT which showed no abnormal FDG. Stimulated thyroglobulin then was 12 ng/mL. Two years post‐radiation therapy, thyroglobulin was <0.1ng/mL.

Discussion: Thyroid cancer arising from ectopic thyroid tissue is rare. Most common treatment approach is surgical excision of the lesion and/or radioactive iodine therapy. Very few cases with advanced disease undergo external radiation therapy. In this case, the patient underwent external beam radiation therapy, with no evidence of biochemical or structural disease at two years post‐treatment.

POSTER 437

Thyroid Cancer Case Study Poster

DIFFERENTIATED THYROID CANCER AND THE CO‐OCCURRENCE OF A PRIMARY LUNG MALIGNANCY

Marnie Aguasvivas*, Timothy Kearney, Rebekah Campbell, Pamela Schroeder

MedStar Union Memorial Hospital, USA

Introduction: Differentiated thyroid carcinoma (DTC) accounts for >90% of thyroid cancers, and the long‐life expectancy of patients with DTC could be a factor in the detection of other primary cancers. Retrospective data has shown the association of thyroid cancer with synchronous nonthyroidal primary malignancies, but causality is not documented. We present a case of a patient with a primary lung adenocarcinoma metastasis in a mediastinal lymph node unexpectedly found during total thyroidectomy.

Case description: A 66‐year‐old female with history of right upper lobe non‐small cell lung carcinoma treated with lobectomy 7 years prior was found to have multinodular goiter on surveillance CT scan of the lung. She had hyperthyroidism with negative thyroid antibodies. Thyroid uptake scan showed multiple right sided hyperfunctioning nodules and one hypofunctioning left nodule. Ultrasound‐guided fine‐needle aspiration of the left nodule was benign. Repeat ultrasound one year post biopsy showed increased volume of all thyroid nodules compared with baseline. She had compressive symptoms and underwent total thyroidectomy. During the procedure, a small abnormal‐appearing lymph node in level VII was removed and sent to pathology. The pathology showed a right 1.3‐cm noninvasive follicular thyroid neoplasm with papillary‐like nuclear features and a right 2.5‐mm micropapillary thyroid cancer. She was also found to have a metastatic adenocarcinoma consistent with lung cancer involving one mediastinal/level VII lymph node. Genomic panel demonstrated the lymph node to be positive for CBL and DNMT3 genomic alterations.

Discussion: A large population‐based analysis of second cancers in patients with thyroid cancer suggested an increased risk of cancers in all sites, but most commonly kidney, salivary gland, lymphoma and leukemia. Synchronous presentation of lung cancer and DTC has not been commonly reported. Possible explanations of this association include increased surveillance, treatment side effects of the first‐ diagnosed cancer or due to shared environmental or genetic factors. Contrasting with our case, genetic alterations in the DNMT3A gene has been associated with poorly differentiated thyroid cancer, highlighting the importance of further investigation of the genomes associated with thyroid cancer and the association with other non‐thyroidal cancers.

POSTER 438

Thyroid Cancer Case Study Poster

THE ROLE OF MEK INHIBITORS IN PAPILLARY THYROID CANCER: A CASE REPORT

MARIA PESANTEZ*¹, CARLOS PEREZ², SILVIA GRA¹

¹UNIVERSITY OF MIAMI, USA,²Rutgers Health/Trinitas Regional Medical Center, USA

Introduction: Molecular markers may aid in the differentiation of Papillary thyroid cancer(PTC) and predict the response to treatment. BRAF mutation, for example, activates the MAPK pathway and correlates with response to radioactive iodine(RAI) therapy. Radioiodine avidity decreases in high tumor burden patients as thyroid cells lose the ability to uptake iodine.

NF1 gene mutation can be recognized in certain patients with PTC. Usually mutually exclusive with BRAF, it regulates the RAS/MEK pathway, causing uncontrolled replication. It is more common in men and commonly associated with lateral cervical lymph node metastasis. Targeted therapy with MEK inhibitors could increase sensitivity to RAI and BRAF inhibitors.

Case: 62 year old male presenting to our clinic for a follow up on Papillary thyroid cancer with metastasis to mediastinum and left scapula. Despite being compliant with levothyroxine, the last Thyroglobulin was 1510 and TSH21.

Patient underwent a total thyroidectomy seven years prior. Sentinel node biopsy was positive. He completed radioactive Iodine(RAI) therapy with 100mCI. One year after diagnosis, a CT Neck revealed a right neck lymph node and biopsy confirmed metastatic thyroid cancer. A right radical lateral neck dissection was performed followed by RAl with 200mCl. Ten months after surgery, a palpable right upper neck mass was noticed. A right lateral neck dissection with partial excision of right internal jugular was performed. A follow up CT showed right pretracheal and paratracheal soft tissue densities measuring 2.5cm and 1.6cm. In addition, a 3.3 mass in the upper pole of the left kidney was incidentally found and was later diagnosed as renal cell carcinoma. Patient was then started on Lenvatinib, however in the following 6 months the right paratracheal densities increased in size. Lenvima was stopped, and 15 radiation sessions were completed. A MEK inhibitor was started after a NF1 mutation was found. However, 6 months later, he was he was found to have a metastatic lesion in the left scapula managed with palliative radiation

Discussion: MEK inhibitors could be helpful in advanced, RAI resistant thyroid cancer. Studies have shown that targeted therapy may ‘sensitize’ the thyroid cells to take up RAI. Unfortunately in this instance, MEK inhibitors were started after receiving RAI twice and failing multiple lines of treatment. This case highlights the importance of considering targeted therapy early in the treatment of thyroid cancer.

POSTER 439

Thyroid Cancer Case Study Poster

SELPERCATINIB INCREASES THE RADIOACTIVE IODINE AVIDITY IN AN ADOLESCENT WITH RET FUSION‐POSITIVE METASTATIC PAPILLARY THYROID CARCINOMA

Priya Mahajan*^1,2, Andrew Sher³, Samara Potter^4,5

¹Department of Pediatrics, Baylor College of Medicine, USA,²Texas Children's Cancer Center, USA,³Department of Radiology, Texas Children's Hospital, USA,⁴The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, USA,⁵Department of Pediatrics, The Ohio State University, USA

Introduction: RET fusions have been reported in 22% to 45% of children and young adults with papillary thyroid carcinoma (PTC). Selpercatinib, a highly selective RET inhibitor, is FDA approved in children 12 years and older with radioactive iodine (RAI) refractory advanced or metastatic RET altered PTC. Targeted kinase inhibitors have demonstrated high response rates in PTC, and a few case reports have described resensitization to RAI therapy after use of such oncogene specific agents.

Description of the Case: A 16‐year‐old female presented with a one year history of a neck mass. Thyroid ultrasound showed a solid mass with echogenic foci completely infiltrating the left lobe, and a 1.2 cm solid mass within the right lobe. Bilateral cervical, pretracheal, and suprasternal lymphadenopathy was noted. Computed tomography (CT) of the chest demonstrated innumerable bilateral pulmonary nodules. Biopsy of the thyroid nodules and lateral cervical lymph nodes demonstrated PTC harboring a RET‐NCOA4 fusion. Patient underwent a total thyroidectomy and a bilateral central and lateral lymph node dissection. TNM staging was T3bN1bM1. Post surgical diagnostic I‐123 whole body scan (WBS) revealed no iodine avid disease; TSH stimulated Tg was 285.5 ng/mL. RAI was deferred given no iodine avid disease and patient was started on oral selpercatinib 160 mg twice a day. Patient received 5 months of selpercatinib with no adverse events. Repeat CT chest showed a decrease in size of the bilateral pulmonary nodules, with no new nodules noted. Repeat I‐123 WBS demonstrated iodine uptake in the lungs exclusively; TSH stimulated thyroglobulin was 102.5 ng/mL. Patient received 146 mCi I‐131 and post‐RAI WBS demonstrated iodine uptake overlying the chest. Selpercatinib therapy was discontinued and patient remains clinically well.

Discussion: Selpercatinib increases RAI avidity in adolescents with metastatic RET fusion‐positive PTC. Further investigations into the use of targeted therapies prior to RAI therapy or to resensitize patients to RAI therapy in patients with metastatic fusion positive PTC are warranted.

POSTER 440

Thyroid Cancer Case Study Poster

TUMOR‐TO‐TUMOR METASTASIS: RENAL CELL CARCINOMA METASTATIC TO FOLLICULAR VARIANT PAPILLARY THYROID CARCINOMA

Shourya Tadisina*¹, Daniel Mettman², Maricel Ridella^2,1

¹UMKC, USA,²KCVA, USA

Introduction: Primary thyroid malignancies are increasing in incidence, but metastatic tumors account for only 2‐3% of thyroid malignancies. Metastasis to the thyroid from different primary solid malignancies and the coexistence of different primary thyroid cancers is not unheard of. Tumor to tumor metastasis is extremely rare and we report a case where the primary thyroid tumor is a recipient for metastasis from renal cell carcinoma(RCC).Only 11 other cases have been reported thus far based on literature review.

Case Description: A 65‐year‐old male with a history of RCC status post left radical nephrectomy 7 years ago; pT3aNx was being evaluated for multinodular goiter (MNG). He had a 2.1 cm TIRADS 5 suspicious nodule in the right inferior thyroid which was biopsied by fine needle aspiration (FNA) and showed atypical epithelial cells with focal papillary architecture, pleomorphic cells and cell block preparation was positive for CAIX (renal cell marker), another cell population was positive for TTF1 and PAX‐8. Final cytology consistent with atypia of undetermined significance/ follicular lesion of undetermined significance (AUS/FLUS).Molecular testing came back positive level 2. Patient decided to monitor with serial imaging. Follow‐up thyroid ultrasound (US) showed an increase in size of the nodule by >20% in a year. Referral was made to an ENT surgeon and a right hemithyroidectomy was performed. Surgical pathology report confirmed metastatic clear cell renal cell carcinoma 3 cm, completely excised. Infiltrative follicular variant papillary thyroid carcinoma was 1‐3 cm not precisely determined as tumor was fragmented with RCC. On review of all previous records we identified the presence of MNG over a decade ago but was never biopsied or followed up until now.So, was sent for completion left hemithyroidectomy and pathology revealed two papillary microcarcinomas with infiltrative follicular variant and no RCC.

Discussion: Tumor to tumor metastasis is extremely rare and requires strict criteria for diagnosis that the recipient must be a true neoplasm and there must be true metastasis from the donor tumor. Recurrence of RCC after nephrectomy is unpredictable and can present as late metastasis several years after initial diagnosis. In our case patient had MNG even before the diagnosis of RCC. The right thyroid nodule was never biopsied but had >50% increase in size. Metastatic RCC should always be considered as a possibility when clear cells are identified in the thyroid nodule FNA biopsy and when there is a previous history of RCC.

POSTER 441

WITHDRAWN

POSTER 442

Thyroid Cancer Clinical Poster

REAL‐WORLD TREATMENT PATTERNS AND CLINICAL OUTCOMES IN ELDERLY RADIOIODINE‐REFRACTORY DIFFERENTIATED THYROID CANCER (RAI‐R DTC) PATIENTS TREATED WITH LENVATINIB MONOTHERAPY

Olivera Rajkovic‐Hooley¹, Jingchuan Zhang*², Neil Reynolds¹, Gary Milligan¹, Francis Worden³

¹Adelphi Real World, United Kingdom,²Eisai Inc., USA,³University of Michigan Health System, USA

Objective: Lenvatinib was approved for the treatment of patients with radioiodine‐refractory differentiated thyroid cancer (RAI‐R DTC) in the United States (US) in 2015. In the current analyses we aim to assess real‐world clinical effectiveness in elderly (≥65 years) RAI‐R DTC patients treated with first line lenvatinib monotherapy in the US.

Methods: We conducted a retrospective patient chart review of RAI‐R DTC patients who initiated lenvatinib monotherapy as first line treatment between February 13, 2015 and September 30, 2020. Data were abstracted by prescribing physicians from individual patients' electronic health records. All patient data were de‐identified prior to analyses. Clinical outcomes included real‐world best overall response (rwBOR, as recorded in patients' electronic health records), real‐world progression‐free survival (rwPFS), and overall survival (OS). Time to event endpoints were assessed using Kaplan‐Meier methods in a cohort of patients who were ≥65 years at the time of initiation of lenvatinib treatment.

Results: 108 RAI‐R DTC patients were ≥65 years at lenvatinib initiation, with a median age of 70 years. Within this patient cohort, 48.2% were female, 78.7% were White/Caucasian and 13.9% were African American. At the initiation of lenvatinib, 63.9% had ECOG score of 0 or 1. Common sites of metastases included lymph nodes, lung, bone, and liver. Over the available follow‐up period, 43.5% of patients discontinued first line lenvatinib. Median duration of lenvatinib treatment was 16.7 months overall. Provider‐reported rwBOR during lenvatinib treatment was reported to be complete or partial response in 62.0% of patients. Median rwPFS was not reached. Estimated rwPFS rates at 12 and 48 months since the initiation of lenvatinib treatment were 72.7% and 52.1%, respectively. By the end of follow‐up, 63.9% of the patients were still alive. Median OS was not reached. OS rates at 12 and 60 months since the initiation of lenvatinib treatment were estimated to be 83.3% and 64.3%, respectively.

Conclusion: Our analyses results showed clinical effectiveness of lenvatinib in elderly patients with RAI‐R DTC in real‐world clinical practice in the US.

POSTER 443

Thyroid Cancer Clinical Poster

EXTERNAL BEAM RADIATION THERAPY FOR RECURRENT OR RESIDUAL THYROID CANCER: WHAT IS THE BEST TIME AND THE BEST CANDIDATE FOR A LONG TERM LOCAL DISEASE CONTROL?

Lara Cavalcante^1,2, Natalia Treistman^1,2, Fabiola Gonzalez¹, Pollyanna Fernandes¹, Fernanda Andrade¹, Paulo Alves‐Junior¹, Rossana Corbo¹, Daniel Bulzico¹, Fernanda Vaisman*^1,2

¹Instituto Nacional do Cancer, Brazil,²Faculdade de Medicina, Universidade Federal do Rio de janeiro, Brazil

Objective: The aim of this study was to determine clinical and molecular features that could predict the best candidates for External Beam radiation Therapy (ERBT) for local disease control and the best therapy sequencing regarding radioiodine (RAIT) and ERBT

Methods: we retrospectively reviewed thyroid cancer patients treated with ERBT for macroscopic residual disease or recurrent disease and performed molecular analysis in the primary tumor

Results: Between January 1995 and May 2022, 71 adults, median age of 61 years (range 33‐81), were included. Majority were females, 21.5% had T3 tumors, and 43% T4. Lymph node involvement was present in 43% and distant metastasis in 46,8%. Papillary thyroid carcinoma corresponded to 70.8%. According to the indication for EBRT, 64.6% were treated for gross residual cervical disease and35.4% treated for recurrent lymph node metastasis. The group that presented cervical progression consisted of older patients (63.1 vs 59.3, p = 0.01) and with a higher number of lymph nodes affected (12.1 vs 2.8, P = 0.04). Patients who underwent EBRT for the residual macroscopic disease had a worse overall survival (OS) than those whose reason for EBRT was recurrent lymph node disease (13.3 vs 7.5, p = 0.02). As for the timing of RAIT concerning EBRT, we found that in patients who underwent RAIT after EBRT the disease free survival was higher than that of patients who experienced it before (56.3 vs 17.7, p = 0.032). Regarding molecular analysis, 12.5% had BRAF alterations, 2.5% P53, 1.3 DICER1, 2.5% FAT1, 1.3 ROS1 11.3, NTRK 2.5%, NF1 1.3%, RET 2.5%, ERBB2 1.3%, KRAS 2.5% and TERT 2.5%. However, there was no statistically significant difference in cervical outcomes response among different molecular profiles.

Discussion/Conclusion: Our data show that younger patients, without residual macroscopic disease after surgery, with fewer affected lymph nodes and with ERBT performed less than 2 years after surgery and that had RAIT after ERBT had better cervical disease control. Also worse OS was seen in patients who underwent EBRT for gross residual disease. Further studies are necessary to clarify the role for molecular testing to tailor better candidates for cervical ERBT.

POSTER 444

Thyroid Cancer Clinical Poster

THE MIR‐146B‐5P EXPRESSION LEVELS IN FINE‐NEEDLE ASPIRATION PREDICTS CLINICAL‐PATHOLOGICAL PHENOTYPES ASSOCIATED WITH WORST PROGNOSIS IN DIFFERENTIATED THYROID CARCINOMAS

Marcos dos Santos*¹, Isabela Martins¹, Andrei de Oliveira¹, Bruno Fredi¹, Miriane de Oliveira¹, Bruna Rabelo¹, Nathalia Rodrigues¹, Diego Vilela¹, Bruna Rodrigues¹, Rosália Padovani², Gustavo Cunha², Carolina da Silva², Antonio Bertelli²

¹Onkos Molecular Diagnostics, Brazil,²Santa Casa de Sao Paulo School of Medical Sciences, Brazil

Objective: Many studies suggested the association between the high expression of the microRNA‐146b‐5p (miR‐146b) in differentiated thyroid carcinomas (DTC) and worst prognostic outcomes. In this study, our objective was to define cut‐offs and characterize the miR‐146b expression as a prognostic biomarker for preoperative early identification of clinical‐pathological phenotypes associated with potentially aggressive behaviors in DTC using fine‐needle aspiration (FNA) smear slides, allowing a more accurate clinical management of patients.

Methodology: The cohort of this study consisted of 173 nodules of DTC. The microRNA and DNA were obtained using the preoperative FNA smear slides. All samples were subjected to analysis of miR‐146b expression and the presence of BRAF V600E by qPCR. The patients' anatomopathological reports were examined and clinical‐pathological characteristics were identified: Extrathyroidal Invasion (EI), Vascular Invasion (VI), Lymph Node Metastasis (LNM) and ATA Recurrence Risk (RR). Using the Receiver Operator Characteristic (ROC) curve, two miR‐146b expression cut‐offs values for each characteristic were defined, generating three “miR‐146b expression zones”: low, moderate and high. All results were calculated using the 95% Confidence Interval (CI).

Results: Based on the normalized miR‐146b expression, the risk of developing each characteristic in the respective “miR‐146b expression zones” were: Presence of LNM ‐ 9.1% (CI 4.0% to 17.1%) (low), 32.1% (CI 15.8% to 52.3%) (moderate) and 75.0% (CI 19.4% to 99.3) (high); Probability of being Intermediate/High risk at ATA RR ‐ 13.7% (CI 8.3% to 20.8%) (low), 51.1% (CI 35.7% to 66.3%) (moderate) and 66.7% (CI 22.8% to 95.6%) (high); Presence of BRAF V600E ‐ 7.4% (CI 3.0% to 14.5%) (low), 68.8% (CI 41.3% to 88.9%) (moderate) and 92.9% (CI 66.1% to 99.8%) (high). The miR‐146b expression did not correlate with presence of EI or VI.

Discussion/Conclusion: The results suggested that miR‐146b normalized expression can be considered as a prognostic biomarker to predict relevant clinical‐pathological phenotypes and potential aggressive behaviors of DTC in the preoperative setting.

POSTER 445

Thyroid Cancer Clinical Poster

SURVIVAL BENEFITS FROM EXTENSIVE SURGERY FOR PAPILLARY THYROID MICROCARCINOMA

Marcela Herrera*, Mohamed Hussein, Emily Persons, Eman Toraih

Tulane, USA

Background: Papillary Thyroid Microcarcinoma (PTMC) is attributed to the rise in the incidence of thyroid cancer. Treatment for PTMC is still variable; the current ATA guidelines recommend hemithyroidectomy. However, studies have shown an increase in PTMC patients undergoing total thyroidectomy.

Aim: This study aims to determine whether extensive surgery (total thyroidectomy) for PTMC patients has any survival benefits compared to non‐extensive surgery (subtotal, lobectomy, or less than lobectomy).

Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries 17 and 22 were used to include patients over the age of 22 with a single thyroid cancer record of either follicular or papillary thyroid carcinoma. Patients with other prior cancers, radiotherapy, or thyroid cancer diagnosed at autopsy were excluded. Cox proportional hazards, univariate, and multivariate logistic regressions were performed in addition to Kaplan‐Meier survival curves to analyze the data.

Results: In the study, 60.2% of the 6,064 patients underwent extensive surgery, while 39.8% underwent a non‐extensive procedure. The participants were mainly female (82.1%, p = 0.012). Those who had extensive surgery were more likely to receive RAI (19.6% vs 3.4%, p < 0.001). The Kaplan‐Meier plot indicated that those who underwent total thyroidectomy had a higher overall survival (p = 0.001) and a significantly lower risk of recurrence (OR = 0.07, p = 0.01) than those who did not have an extensive procedure. However, there was no statistically significant difference in risk of second primary cancer between the two groups (p = 0.74).

Conclusion: Our findings suggest that extensive surgery is the preferred treatment for patients with PTMC, and surgeons should consider the increased overall survival of extensive thyroid surgery when drafting a treatment plan for patients with PTMC.

POSTER 446

Thyroid Cancer Clinical Poster

CLINICAL CHARACTERISTICS AND SIGNIFICANCE OF DICER1 MUTATION IN DIFFERENTIATED THYROID CANCER

Cong Shi, Wen‐Ting Guo, Xin Zhang, Zhuan‐Zhuan Mu, Di Sun, Yu‐Qing Sun, Yan‐Song Lin*

Peking Union Medical College Hospital, China

Objective: DICER1 mutation has been described with increasing frequency in differentiated thyroid cancer (DTC). This study aimed to investigated the association of DICER1 with clinical significance as well as radioactive iodine reponse of DTC.

Method: A total of 313 FFPE samples from patients with DTC who underwent total thyroidectomy between 2011 and 2022 were collected and targeted next‐generation sequencing was performed by ThyroLead panel with 26 genes included. The clinicopathological characteristics and response to radioiodine therapy, particularly radioactive iodine‐refractory (RAIR) status of patients with DICER1 point mutation were retrospectively analyzed.

Results: A total of 313 DTC patients with intermediate or high risk features were included in our cohort. The overall prevalence of DICER1 mutation was 7.3% (23/313) in DTC patients with a mean age at diagnosis of 36.6 ± 15.3 years old. Comparing with DICER1 mutation‐negative, larger primary tumor (P = 0.008) and more aggressive pathological type (P < 0.001) was observed in DICER1 mutation‐positive patients. Comparing with no mutation wild type group, more advanced AJCC T staging occurred in DICER1 mutation alone group (III/IV occurrence 100% vs. 42.9%, P = 0.04) except difference in primary tumor size (P = 0.002) and pathological type (P = 0.01). Of note, 69.6% (16/23) DICER1 mutated patients were identified coexisting with other active genetic alterations implicated with aggressive DTC evolvement, including BRAF, TP53, TERT promoter mutations, and RET fusions. Among these DICER1 co‐mutation patients, except for the features of larger primary tumor size(P = 0.04) and more aggressive pathological type (P < 0.0001), worse response to RAI therapy was also observed, indicating the possible synergistic role of DICER1 mutation in promoting the progression of DTC, even loss of RAI avidity, and poor response to RAI therapy.

Conclusion: In this Chinese DTC cohort with intermediate or high risk features, DICER1 mutation was revealed to associate with large tumor size, aggressive pathological type, and advanced TNM staging. The more common coexistence of DICER1 mutation and aggressive genetic events such as BRAF, TP53, and TERT promoter mutations suggested it might play synergistic role in promoting the progression of DTC, even loss of RAI avidity, and poor response to RAI therapy.

POSTER 447

Thyroid Cancer Clinical Poster

THE MULTI‐INSTITUTIONAL MEDULLARY THYROID CANCER COLLABORATIVE REGISTRY (MTCC): CAN A RARE TUMOR REGISTRY ACCURATELY REPRESENT ALL PATIENTS WITH THE DISEASE?

Thomas Szabo Yamashita*¹, Michelle Mulder², Alyssa Cortella², Chiung‐Hiu Huang², Hui Zhao¹, Susan Peterson¹, Mimi Hu¹, Mark Zefereo¹, Jessica Gosnell², Julie Sosa², Elizabeth Grubbs¹

¹MD Anderson Cancer Center, USA,²University of California San Francisco, USA

Objective: Utilization of large databases, such as the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, is necessary to study rare tumors such as medullary thyroid cancer (MTC) but they lack data to understand the natural history. The multi‐institutional Medullary Thyroid Cancer Collaborative Registry (MTCC) is a comprehensive longitudinal collection of demographic, clinical, and pathologic data and patient‐reported outcomes. We compared clinical and demographic characteristics of patients enrolled in MTCC with a state registry and SEER.

Methods: MTCC registrants' demographic and clinical characteristics were compared with Texas Cancer Registry (TCR) and SEER, 1995‐2018. MTCC enrollment occurs at tertiary care centers and through patient support organizations.

Results: 1239 patients were identified in MTCC, 257 in TCR and 3890 in SEER. Percentage of patients <19 years and 20‐54 years in MTCC was 14% and 59%, 5% and 47% in TCR(p < 0.0001) and 4% and 44% in SEER (p < 0.0001). Female sex was 56% in MTCC, 65% in TCR(p = 0.004) and 58% in SEER(p = 0.11). Percentage of Hispanic and African American patients was 10% and 4% for MTCC, 27% and 10% for TCR (p < 0.001), 15% and 8% for SEER(p < 0.001). The MTCC cohort presented with more advanced T and N stages [MTCC 28% T3‐4 and 49% N1; TCR 10% T3‐4, 30% N1 (p < 0.001); SEER 25% T3‐4, 40%N1 (p < 0.001)]. Prevalence of M1 disease was 10% in MTCC, 9% in TCR (p = 0.79) and 10.4% in SEER (p < 0.001). In MTCC, a higher percentage of patients underwent total thyroidectomy, and a lower percentage had no surgical interventions: 87% and 1%, vs 74% and 9% in TCR (p < 0.0001) and 83% and 9% in SEER(p < 0.0001). Eleven percent of MTCC patients received chemotherapy vs 4% of TCR patients(p < 0.001), data point unavailable in SEER.

Discussion/Conclusion: The clinico‐demographic profile of MTC patients in the MTCC differs from two population‐based databases, with lower proportions of Hispanic and African American patients and higher proportion of younger patients. Moving forward, MTCC enrollment efforts should focus on enhancing recruitment of these underrepresented groups by utilizing community engagement techniques, patient stakeholder involvement and inclusion of languages other than English to better capture the true presentation of the disease.

POSTER 448

Thyroid Cancer Clinical Poster

ANALYTICAL PERFORMANCE COMPARISON BETWEEN THE OLD AND THE NEW VERSION OF A MICRORNA AND DNA‐BASED MOLECULAR CLASSIFIER FOR INDETERMINATE THYROID NODULES IN A REAL‐WORLD COHORT OF SAMPLES

Marcos dos Santos*, Andrei de Oliveira, Diego Vilela, Bruna Rodrigues, Bruno Fredi, Isabela Martins, Miriane de Oliveira, Bruna Rabelo, Nathalia Rodrigues

Onkos Molecular Diagnostics, Brazil

Objective: In 2018 we presented the first version (v1) of our microRNA‐based algorithm for indeterminate thyroid nodules classification, which has being used in real‐world clinical routine until recently, when an optimized version (v2) was released using new machine learning techniques and adding DNA analysis to microRNA data. Here, we aimed to simulate and observe what the performance of v2 would have been, if it had been used in the classification of the same samples classified by v1 in the real‐world clinical routine.

Methods: The cohort of this study was composed of thyroid FNA smear slide samples of 1718 nodules (from 1687 patients) (945 Bethesda III and 773 Bethesda IV) that were originally classified by v1 had the microRNA and DNA data re‐analyzed and classified by v2. The molecular analysis performed in the samples consisted of microRNA profile and DNA mutation analysis (BRAF V600E and pTERT C228T/C250T). From those, anatomopathological data was available for 329 nodules (112 benign and 217 malignant) and used to evaluate the performance of v2. Due to the unrealistically high disease prevalence (66.0%), a real‐world adjusted prevalence (32%) was performed based on Bayes´ theorem.

Results: When comparing the results of v1 vs v2, 979 vs 1175 samples were classified as negative (Benign Call Rate/BCR ‐ 57.0% vs 68.4%) and 739 vs 543 samples as positive. In this simulation, the real‐world performance of v2 would be: 94.5% of sensibility, 75.9% of specificity, 64.8% of positive predictive value (PPV), 96.7% of negative predictive value (NPV) and 81.8% of accuracy.

Discussion/Conclusion: The results show an BCR improvement in performance of v2 compared to v1, resulting in an increment of the number of cases that would have been benefited from the test avoiding unnecessary surgeries. The v2 also showed high PPV and NPV, suggesting that real‐world performance will also be optimized.

POSTER 449

Thyroid Cancer Clinical Poster

ANTIRESORPTIVE THERAPY PREVENTS MORBIDITY IN THYROID CANCER PATIENTS WITH BONE METASTASES: A CLINICAL‐GENOMIC STUDY

Athanasios Bikas*¹, Sara Ahmadi¹, Theodora Pappa^1,2, Freddy Toloza Bonilla¹, Benjamin Altshuler¹, Pingping Xiang¹, Jacob Haase¹, Ellen Marqusee¹, Kartik Sehgal², Iñigo Landa¹, Erik Alexander¹

¹Brigham and Women's Hospital, USA,²Dana Farber Cancer Institute, USA

Introduction/Objective: Osseous metastases (OM) confer increased morbidity and mortality in patients with thyroid cancer. There is still very limited information on the genomic background of OM in thyroid cancer. Moreover, the role of antiresorptive therapy (ARx) is still being debated as it has also been postulated ARx can cause osteonecrosis of the jaw (ONJ) when combined with tyrosine kinase inhibitors (TKI). The objective of the current study was to explore the genomic background of OM in thyroid cancers, and examine the risk‐benefit ratio of ARx in OM.

Methods: We performed a clinical–genomic analysis of consecutive patients with OM from differentiated (DTC), poorly differentiated (PDTC), anaplastic (ATC) and medullary thyroid cancers (MTC), who underwent surgery or received advanced therapy at our institution. For a subset of our cohort, custom‐targeted next generation sequencing was performed. We compared clinical features and outcomes based on administration of ARx. Skeletal‐related events (SRE) were defined as surgery or radiation to OM, pathologic fracture, cord compression or hypercalcemia of malignancy.

Results: A total of 148 thyroid cancer patients with OM were included (47% DTC, 13% PDTC, 14% ATC, 26% MTC). Sixty patients had genomic characterization through NGS. In follicular cell‐derived cancers, 27 tumors had other oncogenic mutations apart for RAS or BRAFV600E, including PIK3CA, PTEN, TERT promoter, TP53, ARID1A, ARID1B, ARID2 and CDKN2A. No additional oncogenic mutations were found in MTCs, other than RET and RAS. Sixty‐five patients (65/148, 45%) were treated with antiresorptive therapy for a median duration of 6 months, and the vast majority (85%) were placed on ARx after a SRE had already happened. Although patients on ARx had more significant bone disease as shown by more total SREs, ARx prolonged SRE‐free survival (2 months before ARx vs. 11 months after ARx, p = 0.019). Five cases of ONJ were observed (5/148, 3%). No statistically significant difference was found in the ONJ incidence between the patients that received ARx alone or in combination with TKIs (p = 0.63).

Discussion/Conclusion: ARx prevents morbidity in thyroid cancer, producing a favorable risk‐benefit ratio, and should be considered especially in patients with extensive OM. Genomic profiling of patients with OM might help explain the heterogeneity of the disease.

POSTER 450

Thyroid Cancer Clinical Poster

DIAGNOSTIC PERFORMANCE OF THE THYGENX AND THYRAMIR PLATFORM FROM INTERPACE DIAGNOSTICS IN NON‐DIAGNOSTIC THYROID NODULES

Peter Issa*¹, Tyler Metz², Aaron Albuck², Alexandra LaForteza², Ali Abdelhady², Mohamed Shama², Younes Aljohmani², Krzysztof Moroz², Eman Toraih², Emad Kandil²

¹LSU Health Sciences Center, USA,²Tulane University, USA

Objective: Approximately 10%–34% of thyroid nodules sent for cytological analysis are read as non‐diagnostic. The genetic testing platform ThyGeNEXT and ThyraMIR by Interpace Diagnostics has been marketed as a suitable test for the assessment of non‐diagnostic nodules. To our best knowledge, no studies have investigated the diagnostic accuracy of the ThyGeNEXT and ThyraMIR platform in this setting. We aimed to assess the diagnostic performance of the ThyGeNEXT and ThyraMIR genetic testing platform in non‐diagnostic thyroid nodules at a single institution.

Methods: Patients with non‐diagnostic thyroid nodules from November 2016 to November 2021 with genetic testing and who underwent subsequent thyroid surgery were included. All nodules underwent ThyGeNEXT and ThyraMIR genetic testing. Nodule preoperative biopsy sites were matched to nodules surgical pathology. Using surgical pathology as the standard, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR).

Results: A total of 44 nodules were non‐diagnostic were included. Of these, 4 (10.0%) were read as insufficient allowing the diagnostic assessment of 40 nodules. The specificity of the test was 88.57%. The sensitivity was 20.0%. The single true positive identified was a patient with a medullary thyroid carcinoma. The NPV was determined to be 88.57%. There were four nodules preoperatively misidentified to be benign (false negatives), three of which were malignancies <5 millimeters (mm) on surgical pathology. These incidental malignancies were likely not sampled, which might have improved the NPV to 96.88%. The remaining false negative nodule was 18 mm in largest diameter. All missed malignancies were papillary thyroid carcinoma.

Discussion: The Interpace Diagnostics genetic testing platform ThyGeNEXT and ThyraMIR is a suitable rule‐out test with a NPV of almost 90%. Considering that the majority (75%) of false positives were due to malignancies <5 mm, these microcarcinomas were likely not sampled preoperatively which artificially deflated the true NPV of the test. Genetic testing of non‐diagnostic thyroid nodules using the ThyGeNEXT and ThyraMIR platform enhances patient risk stratification and is a recommended ancillary tool. Future investigation with larger sample sizes are warranted to corroborate and expand on these findings.

POSTER 451

Thyroid Cancer Clinical Poster

FEATURES AND TRENDS OF THYROID CANCER IN ALBANIA FROM 2018 TO 2022

Dorina Ylli*¹, Violeta Hoxha², Ardita Muja¹, Marjeta Kermaj², Klodiana Poshi¹, Ejona Celiku¹, Agron Ylli¹, Majlinda Ikonomi¹

¹University of Medicine, Tirana, Albania,²“Mother Teresa” University Hospital Center, Albania

Background: The incidence of thyroid cancer (TC) has markedly increased, while the associated mortality remains unchanged and has remained relatively low and stable. However, no information is available regarding Albania.

Objectives: This study aims to investigate the features and trends of TC in the past 5 years in Albania.

Methods: Thyroid pathology reports of “Mother Teresa” University Hospital Center (MTUHC) dating from 2018 to 2022, were reviewed. Data regarding age, histology type, vascular and capsular invasions, multifocality, stage, and metastases were obtained. All public hospitals in Albania send their biopsies to MTUHC, thus these results, reflect a nationwide trend of thyroid cancer.

Results: In 3052 thyroid pathology reports, 441 were diagnoses of TC. From 2018 to 2022 the number of patients diagnosed with TC has increased by 40% (79 in 2018, 75 in 2019 88 in 2020, 88 in 2021, and 111 in 2022). The incidence increased from 2.7/100.000 to 3.9/100.000 people‐year. Differentiated TC increased from 89.9% in 2018 to 93.7% in 2022. Instead, medullary and anaplastic cancer decreased from 5.8 to 3.2% and from 4.3 to 2.1% respectively. In the differentiated TC group, an increase of PTC and Hurthle cell carcinoma was observed from 93.5% to 96.6%. and from 1.6% to 2.2% respectively. Follicular TC decreased from 4.8% in 2018 to 1,1% in 2022. The percentage of males varied from 15.9% in 2018 to 39.7% in 2019,17.4% in 2020, 22.5% in 2021, and 18.9% in 2022.

In differentiated thyroid cancer vascular invasion decreased from 25% to 14%, capsular invasion decreased from 65% to 63.6%, and multifocality increased from 11.7% to 19.5%. Lymph node metastases increased from 1.9% to 4.6%. In 2018 microcarcinomas were present in 16.7% of the cases but increased to 54.35% in 2022. The mean age at diagnosis slightly increased from 48 years old to 50 years old.

Discussion: Thyroid cancer cases have increased by 40% in Albania compared to 5 years ago. This may be due to better diagnosis and environmental factors. Whether there is a shift in aggressive behaviors is still unclear. Further studies investigating the prognoses are needed to offer better insight.

POSTER 452

Thyroid Cancer Clinical Poster

A META‐ANALYSIS AND REVIEW OF THE BRAF K601E MUTATION VS. THE V600E MUTATION

Alyssa Webster*¹, Robert Clark¹, Peter Issa², Eman Toraih^3,4, Emad Kandil³

¹Tulane University School of Medicine, USA,²Louisiana State University Health Sciences Center, USA,³Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, USA,⁴Medical Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Egypt

Objective: BRAF is the most commonly mutated oncogene in papillary thyroid cancer (PTC), which has recently been increasing in incidence. Previous studies on BRAF have mostly focused on V600E, the most common BRAF mutant, and have found it is associated with indicators of poor prognosis. However, the second most common BRAF mutation, K601E, has not been studied extensively and exhibits significantly different biochemical and molecular behaviors when compared to V600E. It is almost always seen in tumors with follicular histology, while in comparison V600E is found in many variants of PTC (most commonly the classic variant), but rarely in follicular types. Additionally, recent studies have suggested that K601E may be associated with a more indolent course when compared to V600E. We aimed to review the data on this mutation.

Methods: In this systematic review and meta‐analysis, we seek to analyze cases with BRAF K601E mutations and evaluate whether they can be categorized as distinct from BRAF V600E. Available literature was reviewed between 2003 and 2022.

Results: The histological representation differed between the two mutations, with PTC‐FV comprising the majority (59%) of K601E mutated cancers, while it is the one of the less common PTC variants in V600E mutants (10%). It is also occasionally found in FTC and FA (8% and 6% respectively), compared to V600E which was only found in 1 FTC and 0 FA. V600E mutants are more evenly distributed among non‐follicular histological subtypes, most commonly in the classic variant of PTC (28%). A larger proportion of V600E mutants exhibited local invasion or extrathyroidal extension (∼1.5:1 ratio of no extension to extension) compared to K601E mutants (∼3:1 ratio).

Conclusions: We found an association of K601E mutants with follicular variants of thyroid cancer such as FV‐PTC, FA, and FTC. Our findings may also be consistent with K601E mutants having a more indolent course, but more data is needed to show significance and make clinical recommendations.

POSTER 453

Thyroid Cancer Clinical Poster

EVALUATION OF TRACHEAL INVASION IN PAPILLARY THYROID CARCINOMA BASED ON THE ANGLES BETWEEN TRACHEAL CARTILAGE AND TUMOR SURFACE: DIFFERENCE IN ACCURACY DEPENDING ON SURGEON'S EXPERIENCE

Yasuhiro Ito*, Akira Miyauchi, Hiroo Masuoka, Takuya Higashiyama, Naoyoshi Onoda, Akihiro Miya, Takashi Akamizu

Kuma Hospital, Japan

Objective: It is often difficult to evaluate papillary thyroid carcinoma (PTC) invasion to the trachea when tumors attach it on imaging studies. We previously demonstrated that determining the angles between the trachea cartilage and tumor surface is useful for predicting trachea invasion of PTCs ≤1 cm; if the angle is acute, tumor is unlikely to invade to the trachea, but if tumor forms obtuse angle with the tracheal cartilage, tracheal invasion is suspected. Here we investigated whether this evaluation standard is useful for larger PTCs.

Methods: We enrolled 284 patients with PTC >1 cm touching the trachea on imaging studies: 82 (29%) showed significant tracheal invasion on intra‐operative findings and required airway resection. Two staff surgeons (Surgeon group), two surgical trainees (Trainee group) and two radiology technologists (Radiology group) blindly evaluated the trachea invasion of tumors on CT scan. Trachea invasion was evaluated mainly based on the angles between the trachea cartilage and tumor surface using three categories: positive, indeterminate, and negative.

Results: In tumors touching 1/3 the circumference or less of the trachea, the specificity of the Surgeons group, Trainee group, and Radiologist group was 52, 15, 17%, respectively and the Surgeons group's specificity was significantly higher (p < 0.0001) than the other two groups. The Surgeon group's efficiency was 50%, which was also higher (p < 0.0001) than those of the other groups (21% and 30%). In the subset of tumors touching more than 1/3 the circumference of the trachea, the Surgeon group's specificity became lower, at 27%, but was still higher than that of the Trainee group (5%; p = 0.0253) and that of the Radiology group (11%; p = 0.0758). However, the efficiency did not significantly differ among the three groups (40%, 40%, and 50%).

Conclusions: An evaluation based on the angle between the trachea cartilage and tumor surface is useful not only for PTCs ≤1 cm but also for larger PTCs. Surgeons' clinical experience appears to help them more accurately predict the status of trachea invasion of PTCs. However, lower specificity of the Surgeons group and the lack of difference in efficiency among the three groups in tumors touching more than 1/3 the circumference of the trachea indicates the difficulty of prediction of trachea invasion in PTCs widely attaching to the trachea.

POSTER 454

Thyroid Cancer Clinical Poster

MANAGEMENT OF ELDERLY PATIENTS WITH PAPILLARY THYROID MICROCARCINOMA: ANALYSIS OF PROGNOSIS FOR SURGERY VERSUS NON‐SURGERY

Zihan Xi*, Wenhui Li, Jun Zhou

Department of Breast and Thyroid Surgery Union Hospital, Tongji Medical College Huazhong University of Science and Technology, China

Objective: Papillary thyroid microcarcinoma (PTMC) is one of the most common types of thyroid cancer and the prognosis of patients who have undergone surgery is usually good. However, the risk of surgery is higher in elderly patients than that in younger patients. Surgery as a treatment for elderly patients with PTMC remains controversial. Thus, a retrospective study was performed to evaluate the effect of surgery on the prognosis of elderly patients with PTMC (aged 65 years or older).

Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we carried out a retrospective study to evaluate the clinical significance of surgery and non‐surgery in elderly patients with PTMC. Cox regression analyses were performed to identify the risk factors for these patients. Propensity score matching (PSM) analysis was also conducted to minimize potential selection bias.

Results: We collected data from 8,401 elderly patients with PTMC from SEER. In multivariate Cox analysis before PSM, the independent risk factors of both overall survival and cancer‐specific survival were: age at diagnosis, N category, multifocality, histological grade, and non‐surgery (p < 0.001). In Kaplan‐Meier survival analysis before and after PSM, both overall survival and cancer‐specific survival were better for elderly patients with PTMC who underwent surgery than those without surgery (p < 0.05).

Discussion/Conclusion: Our study indicates that elderly patients with PTMC who underwent surgery had a better prognosis than those who did not. Surgery is positively associated with an improved prognosis, and to some extent recommended for these patients after appropriate risk assessment.

POSTER 455

Thyroid Cancer Clinical Poster

MEDULLARY THYROID CARCINOMA WITH NEGATIVE CALCITONIN STAIN FOR PROVEN METASTASIS

Farah Kitana*, Deema Al‐Souri, Dmitriy Stasishin, Kenneth Burman, Leila Shobab

Medstar Washington Hospital center, USA

Introduction: Medullary thyroid carcinomas (MTC) are Neuroendocrine tumors (NET) of the thyroid gland that derive from parafollicular endocrine cells. MTC is an uncommon thyroid malignancy, accounting to 1 to 10% of all thyroid cancers. It is characterized by a mean survival of 8.6 years, and a 10‐years survival rates ranging from 69 to 89%. Calcitonin is almost always detected in MTC and is an important component of clinical and pathological diagnosis. We report a case of a 72 year‐old female who presents with recurrent medullary thyroid cancer and undetectable calcitonin on serum and tissue immunohistochemistry.

Description of the case:72‐year‐old female patient, presenting with an enlarged lymph node in 2013. Fine needle aspiration biopsy (FNAB) lead to the diagnosis of MTC. She underwent total thyroidectomy and pathology confirmed MTC. In 2017, she presented with recurrence of disease in her cervical lymph nodes. Her calcitonin continued to be negative with a value of <2.

In 2020, patient developed new widespread bony metastasis as well as pulmonary metastasis. Her CEA level was elevated at 332 ng/mL. She underwent Biopsy of right iliac crest. Immunostaining for calcitonin was negative. However, tumor cells were positive for CK 7, chromogranin, synaptophysin, PAX8, and TTF‐1.

Discussion: Infrequently, MTC and NET produce different markers, such as procalcitonin, neuron specific enolase (NSE) and chromogranin A (CgA), without the presence of calcitonin. The prevalence of calcitonin‐negative MTC has been documented as approximately 12% in the literature. High CgA serum levels are characteristic of NETs, which share the same neural crest ectoderm derivation similar to parafollicular C‐cells with MTC. Establishing the diagnosis can be challenging with negative staining for Calcitonin but positive for neuroendocrine markers such as chromogranin A (CgA), synaptophysin, and neuron specific enolase (NSE). Calcitonin negative MTC is a rare and understudied cancer. Diagnosis is often challenging and delayed, due to the lack of elevation of serum markers. These cancers may represent dedifferentiated and more aggressive types of MTC. Further studies are needed to identify new and reliable biomarkers to help with diagnosis.

POSTER 456

WITHDRAWN

POSTER 457

Thyroid Cancer Clinical Poster

SIMULTANEOUS OCCURRENCE OF MEDULLARY THYROID CARCINOMA AND PAPILLARY THYROID CARCINOMA: A CASE SERIES WITH LITERATURE REVIEW

Poupak Fallahi¹, Armando Patrizio*², Giulio Stoppini³, Giusy Elia⁴, Francesca Ragusa⁴, Sabrina Paparo⁵, Eugenia Balestri³, Valeria Mazzi³, Chiara Botrini³, Gilda Varricchi⁶, Salvatore Ulisse⁷, Marco Ghionzoli⁸, Silvia Ferrari⁹, Alessandro Antonell¹⁰

¹Department of Translational Research and New Technologies in Medicine and Surgery, Italy,²Department of Emergency Medicine, Azienda Ospedaliero‐Universitaria Pisana, Italy,³Department of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Italy,⁴Department of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa,, Italy,⁵Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa,, Italy,⁶Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy; World Allergy Organization (WAO), Center of Excellence, Naples, Italy; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, Naples, Italy., Italy,⁷Department of Surgical Sciences, 'Sapienza' University of Rome, Italy,⁸Division of Pediatric Surgery, Department of Surgical Pathology, University of Pisa,, Italy,⁹Department of Clinical and Experimental Medicine, University of Pisa, Italy,¹⁰Department of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, Italy

Abstract

Objective: Papillary thyroid carcinoma (PTC) is the most common type of differentiated thyroid cancer (DTC), while medullary carcinoma of the thyroid (MTC) accounts for the 4%. The concomitant presence of PTC and MTC is rare.

Methods: This is a retrospective, single‐center observational study conducted over 16 years (from 2001 to 2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit‐Department of Medicine of the University Hospital of Pisa (AOUP), Italy.

Results: Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular thyroid carcinoma or hereditary MTC (familial MTC [FMTC]/Multiple Endocrine neoplasia type 2 [MEN2]) was found. Concerning the 5 cases of PTC/MTC, there was a male prevalence (M:F = 3:2) and, at the diagnosis, all PTC components were at stage 1 (100%), whereas MTC counterparts were in stage I and III in 2/5 each (40%), and in stage II in 1/5 patient (20%). 3/5 (60%) MTC patients recovered while patients 2/5 (40%) developed metastatic disease; no recurrence for PTC was detected. The search for germline mutations of the RET gene resulted negative in all 5 patients.

Conclusions: The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of the PTC/MTC forms is still unknown although many believe that this simultaneous occurrence is only a coincidence, but we cannot exclude the hypothesis of a shared genetic origin. The PTC/MTC association does not modify the epidemiological and pathological behavior and clinical characteristics of the cancer forms.

POSTER 458

Thyroid Cancer Clinical Poster

HIGH RATE OF PRIMARY TREATMENT FAILURE AFTER POSTOPERATIVE HIGH DOSE RADIOACTIVE IODINE IN DIFFERENTIATED THYROID CANCER PATIENTS

Ralf Paschke, Jiahui Wu, Parthiv Amin, Sana Ghaznavi*

University of Calgary, Canada

Objective: Initial postoperative RAI dose is determined based on a patient's risk of disease‐related mortality and recurrence. Patients receiving initial high dose RAI (³ 100 mCi) typically have high risk features such as local tumour invasion, bulky lymphadenopathy, or distant metastatic disease. We evaluated the natural history of differentiated thyroid cancer (DTC) patients treated with ³ 100 mCi RAI.

Methods: using our institutional prospective thyroid cancer database, we identified DTC patients treated with an initial postoperative RAI dose ³ 100 mCi between 2017‐2022, with a minimum follow up of one year. Our primary outcome was the rate of primary treatment failure, as defined by structural incomplete response.

Results: Among 763 database patients, we included 111 DTC patients with median age at diagnosis of 51 years (range 14‐84), 54% female, and 86% papillary histology. The ATA risk of recurrence was: low (n = 1, 1%), intermediate (n = 13, 12%), high (n = 97, 87%). Initial treatment included: total thyroidectomy (n = 110, 99%), central neck dissection (n = 77, 69%), lateral neck dissection (n = 65, 59%), and external beam radiotherapy (n = 11, 10%). The initial postoperative RAI dose was: 100 mCi (n = 89, 80%), 150 mCi (n = 21, 19%), 200 mCi (n = 1, 1%).

The rate of structural incomplete response (SIR) during a median of 44 months of follow up was 42% (n = 47 patients), including locoregional disease [LR] (n = 20, 43%), distant metastases [DM] (n = 23 patients, 49%), and both LR and DM (n = 4, 9%). Management of SIR patients included: observation (n = 21, 45%), additional surgery (n = 10, 21%), additional RAI (n = 12, 26%), systemic therapy (n = 11, 23%), and external beam radiotherapy (n = 1, 2%).

Conclusion: The high rate (42%) of structural incomplete response after high dose (³ 100 mCi) postoperative RAI for treatment of DTC patients illustrates the need for more efficacious treatments, beyond RAI alone, for patients deemed to be at high risk for primary treatment failure.

POSTER 459

Thyroid Cancer Clinical Poster

DIAGNOSTIC ACCURACY OF PREOPERATIVE RADIOLOGIC FINDINGS IN PAPILLARY THYROID MICROCARCINOMA: DISCREPANCIES WITH POSTOPERATIVE PATHOLOGIC DIAGNOSIS AND IMPLICATIONS FOR CLINICAL OUTCOMES

Ying Li*¹, Seul Ki Kwon^1,2, Hoonsung Choi³, Yoo Hyung Kim⁴, Sunyoung Kang^1,2, Kyeong Cheon Jung⁵, Jae‐Kyung Won⁵, Do Joon Park^1,4, Young Joo Park^1,4, Sun Wook Cho^1,4

¹Department of Internal Medicine, Seoul National University College of Medicine, Korea, Republic of,²Department of Internal Medicine, Uijeongbu Eulji Medical Center, Korea, Republic of,³Department of Internal Medicine, Chung‐Ang University College of Medicine, Korea, Republic of,⁴Department of Internal Medicine, Seoul National University Hospital, Korea, Republic of,⁵Department of Pathology, Seoul National University College of Medicine, Seoul National University Hospital, Korea, Republic of

Objective: Active surveillance (AS) has been proposed as an alternative approach to immediate surgery for low‐risk papillary thyroid microcarcinoma (PTMC). However, the accuracy of preoperative radiologic evaluation in predicting tumor characteristics and clinical outcomes remains unclear. This study aimed to access the diagnostic accuracy of preoperative radiologic findings in PTMC and explore their correlation with clinical outcomes.

Methods: A total of 939 PTMC patients who underwent surgery were enrolled. Preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months prior to surgery and compared with postoperative pathologic findings. The discrepancy between preoperative and postoperative tumor sizes were analyzed, and clinical outcomes including distant metastasis and recurrence, were accessed.

Results: The agreement rates between radiological and pathological tumor size was approximately 60%, with a notable discrepancy observed, including an increase in tumor size in 24.3% of cases. 10.8% of patients had postoperative tumor sizes larger than 1 cm, which were initially classified as 0.5‐1.0 cm on preoperative radiologic imaging. Pathologic aggressive factors, including multiplicity, microscopic extrathyroidal extension and LNM were associated with postoperative tumor size >1 cm. Patients with postoperative tumor size >1 cm had a higher risk of distant metastasis compared to those with tumor size ≤1 cm. As for LNM, 30.1% of patients who were not suspected before surgery were diagnosed with LNM after surgery (post‐only LNM). The post‐only LNM group showed smaller metastatic foci and lower risks of distant metastasis or recurrence compared to the pre‐post LNM group, which included patients with lymph node metastasis detected both before and after surgery.

Conclusion: In a subset of PTMCs, tumor size increased and confirmed to be over 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis. These findings improve our understanding of the diagnostic accuracy of preoperative radiologic evaluation in PTMC and provide insights for predicting clinical outcomes based on tumor size.

POSTER 460

Thyroid Cancer Clinical Poster

FIVE‐YEAR OUTCOMES OF PERCUTANEOUSTHERMAL ABLATION FOR THE TREATMENT OF SOLITARY PAPILLARY THYROID MICROCARCINOMA: A MULTICENTER RETROSPECTIVE STUDY

Lin Yan*¹, Jie Ren², Ying Che³, Shurong Wang⁴, Hui Wang⁵, Yukun Luo¹

¹Chinese PLA General Hospital, China,²The Third Affiliated Hospital of Sun Yat‐sen University, China,³First Affiliated Hospital of Dalian Medical University, China,⁴Yantai Hospital of Shandong Wendeng Orthopaedics &Traumatology, China,⁵China‐Japan Union Hospital of Jilin University, China

Objective: To investigate more than 5‐year outcomes of percutaneous thermal ablation (TA) for patients with solitary low‐risk papillary thyroid microcarcinoma(PTMC) in a large multicenter cohort.

Methods: This retrospective multicenter study included 475 patients with solitary low‐risk PTMC treated with TA (358 for Radiofrequency ablation; 117 for microwave ablation) from five centers and followed up for at least 5 years from October 2010 to June 2017. Disease progression including lymph node metastasis(LNM) and recurrent tumors, volume reduction rate(VRR), tumor disappearance rate, complications, and delayed surgery were assessed. A Cox proportional hazards model was used to identify the variables associated with disease progression.

Results: A total of 475 patients(mean age, 44.1 ± 10.4 years, 371 females, 104 males). During the mean follow‐up period of 78.9 ± 14.4 months, disease progression incidence, LNM and recurrent tumors rates were 3.6% (17/475), 1.1% (5/475) and 2.5% (12/475), respectively. No distant metastases were detected. Age <40 years old, male sex, Hashimoto thyroiditisand tumor size were not independent factors associated with disease progression by Cox analysis. The median VRR was 100%, and 471 tumors disappeared(99.2%). Eight patients developed complications(1.7%) and they experienced transient voice change which recovered within 3 months. None of the patients underwent delayed surgery because of anxiety.

Conclusion: This multicenter study revealed that TA was an effective and safe treatment for patients with solitary low‐risk PTMC, which can be offered as a treatment option for the management for low‐risk PTMC.

POSTER 461

WITHDRAWN

POSTER 462

WITHDRAWN

POSTER 463

WITHDRAWN

POSTER 464

Thyroid Cancer Clinical Poster

IMPACT OF RADIOACTIVE IODINE THERAPY ON MENSTRUAL CYCLE AND PREGNANCY (IRON‐MAP) IN WOMEN WITH DIFFERENTIATED THYROID CANCER

Deema Al‐Souri*¹, Lindsey Alpeter¹, Lauren Barrison¹, Azrin Haque Mir², William Kunestner², Serenity Budd³, Rajeev Agrawal³, Neelam Baral¹, Jacqueline Maher⁴, Jacqueline Jonklaas⁵, Veronica Gomez‐Lobo⁴, Kenneth Burman¹, Leonard Wartofsky¹, Leila Shobab¹

¹MedStar Washington Hospital, USA,²Georgetown School of Medicine, USA,³MedStar Health Research Institute, USA,⁴National Institutes of Health, USA,⁵Georgetown University Hospital, USA

Background and Objective: Thyroid cancer (TC) has a striking female predominance with >half of cases occurring before age 50. Radioactive iodine (RAI) therapy is suspected to have deleterious effect on ovarian function but studies on effects of RAI on post treatment reproductive history are lacking. Currently, no guidelines inform fertility planning/preservation. Our primary objective was to evaluate RAI effects on subsequent reproductive events among young women with TC.

Methods and Analysis: Retrospective cohort study based on chart review and telephone interview. We included female patients with TC between 18‐42 years at diagnosis. The treatment in the intervention group was surgery and RAI; the control group received surgery. Patients treated with hormones for gender transformation were excluded. Continuous variables are presented as means (+/‐) SD and compared using a two sample T‐test. Point‐biserial correlation was used to measure strength and direction of associations.

Results: Of 48 patients, 35 received RAI (Intervention) and 13 had surgery only (control). In comparison of intervention to control, average age at diagnosis was similar (30 vs 34yr, p = 0.2).; tumor size was significantly larger (2.2 vs 0.8 cm, p < 0.001); number of pregnancies after treatment was significantly lower (0.38 vs 1.08, p = 0.03). Time since initial treatment was 7.1yr (SD5.0, range 3‐15); average age at menarche was similar in both groups (12.7vs12.6, p = 0.9); average number of RAI‐treatments was 1.2 (SD 0.5) and average cumulative dose was 137mCi 131I (SD 78). 48% of intervention and 38% of control reported irregular menses after treatment (p = 0.5). There was no significant difference in the number of preterm deliveries (0.03 vs 0.15, p = 0.3) and spontaneous abortions (0.09 vs 0.23, p = 0.4) between the intervention vs control groups. 28% of the intervention and 38% of control were unable to conceive after 1‐year of trying (p = 0.6) following treatment. Diagnosis and treatment of TC was associated with significantly lower desire to engage in intimacy in intervention vs control (p = 0.01) and patients in the intervention group had a higher tendency for altered mood (p = 0.07).

Conclusion: Of factors related to the treatment of TC that may have important impact on reproduction, future, long‐term, controlled studies are needed to better understand potential psychological effects.

POSTER 465

Thyroid Hormone Action Metabolism and Regulation Basic Poster

CYSTEINE AND GLYCINE RICH PROTEIN 3, CSRP3, INHIBITS THYROID HORMONE RECEPTOR Β1 PROTEIN DEGRADATION

Dolena Ledee*

Seattle Children's Research Institute, USA,University of Washington, USA

Objective: Thyroid hormones play a critical role in the metabolic phenotype of the heart; and most of the effects involve transcriptional regulation via thyroid hormone receptors (TRs). TRs ability to form combinatorial complexes with an array of partners accounts for TRs physiological flexibility in modulating gene expression. Therefore, the goal of this project was to identify novel proteins that interact with TRβ1in the heart and investigate the functional relationship.

Methods: To identify proteins that associate with TRβ1 in the heart we performed a pull‐down assay on cardiac tissue using GST‐TRβ1 as bait and identified the bound proteins by LC MS/MS. To identify the subcellular localization of TRβ1 and CSRP3 we performed immunocytochemistry. We performed DNA pulldown assay to assess CSRP3 ability to affect TRβ1 binding to its TR elements (TRE) sequence. GST‐pulldown assays were performed to assess the TRβ1 domain that interacts with the CSRP3 protein. To assess CSRP3 effect on TRβ1 protein expression Cos1 cells were transfected with CSRP3 and TRβ1 plasmids and whole cell lysate subjected to western blot analysis.

Results: Cysteine and Glycine Rich Protein 3, CSRP3, was identified as a novel TRβ1 interacting protein. We confirmed CSRP3 colocalized with TRβ1 at location in and outside of the nucleus. GST‐pulldown assays identified the TRβ1 N‐terminal transactivation domain as an important region for binding between TRβ1 and CSRP3. CSRP3 did not affect TRβ1 transcriptional ability and showed no affinity to for TRβ1 TRE sequence. Overexpression of CSRP3 inhibited T3 induced TRβ1degradation.

Conclusion: T3 is known to induce rapid degradation of ubiquitinated TRs, and one form of TRs regulation is the proteasome‐degradation pathway. In this study we identified CSRP3 as a novel protein interacting with TRβ1. CSRP3 acts as an inhibitor to TRβ1degradation, however, the increased TRβ1 levels did not affect the transcriptional activity of the TRβ1 protein. Therefore, increased TRβ1 levels due to CSRP3 overexpression is not a determining factor for repression or activation of transcription.

POSTER 466

Thyroid Hormone Action Metabolism and Regulation Translational Poster

LASN01, A HIGH AFFINITY ANTI‐INTERLEUKIN‐11 RECEPTOR ANTIBODY, BLOCKS PATHOLOGICAL MECHANISMS OF THYROID EYE DISEASE LINKED TO CLINICAL EFFICACY

James Swaney*¹, Toni Jun², Eric Elliott¹, Ivan Lu¹, Shira Geller¹, Merrick Chai¹, Deborah witherden¹, Puneet Arora¹, Rona Silkiss³, David King¹

¹Lassen Therapeutics, USA,²Lassen Therapeutics, USA,³Silkiss Eye Surgery, USA

Objective: Interleukin‐11 (IL‐11), a cytokine in the IL‐6 family, has been implicated in immunofibrotic disease states, especially tissue fibrosis. Recent studies have suggested that IL‐11 is upregulated in thyroid eye disease (TED, also known as Graves' orbitopathy). This study was undertaken to determine if IL‐11 is involved in the pathobiology of TED and to assess the potential therapeutic benefits of blocking the IL‐11 signaling pathway with an anti‐IL‐11R antibody.

Methods: Primary orbital fibroblasts (OF) were isolated from tissue discarded during TED patient decompression surgeries. Either alone, or in combination with other agents, IL‐11 was tested for its ability to stimulate OF proliferation, hyaluronan (HA) production and the induction of markers of fibrosis. Following cell stimulation for 96 hours, HA and fibrotic markers were measured by ELISA. Inhibition studies were also carried out with LASN01, an investigational human antibody that blocks IL‐11 signaling, which is currently in Phase I clinical studies in healthy volunteer subjects.

Results: IL‐11 stimulates OF cell proliferation and the production of extracellular matrix molecules including HA. LASN01, an anti‐IL‐11R antibody currently being studied in a Phase 1 trial, is a potent inhibitor of IL‐11 driven pSTAT3 (canonical) and pERK (non‐canonical) signaling pathways. In OF, LASN01 inhibits production of HA by OF, when stimulated with IL‐11, IGF‐1, or combinations of stimuli, suggesting that IL‐11 may be a novel interventional target in the pathobiology of TED.

Conclusions: IL‐11 is implicated in the pathogenesis of TED, possibly downstream of other known stimuli relevant to TED biology. LASN01 is a potent inhibitor of IL‐11 signaling, leading to the suppression of cell proliferation and HA secretion from TED OF, while also demonstrating anti‐fibrotic activity. For this reason, LASN01 is worthy of further investigation as a potential new therapeutic agent for the treatment of TED.

POSTER 467

Thyroid Hormone Action Metabolism and Regulation Case Study Poster

ORAL LEVOTHYROXINE GIVEN BY ILEOSTOMY IN A COLON CANCER PATIENT WITH PERSISTENT VOMITING

Hearty Yao*, Lizette Kristine Lopez

University of Santo Tomas Hospital, Philippines

A 64‐year‐old Filipino female underwent total thyroidectomy for adenomatous goiter one year ago. She takes 75 micrograms (mcg) of oral levothyroxine daily. She later had colon adenocarcinoma, managed with right hemicolectomy, ileostomy creation, and chemotherapy.

Seven months later, she developed persistent vomiting and epigastric pain. PET/CT scan with contrast revealed a 5‐centimeter pancreatic head mass obstructing the pylorus. She underwent exploratory laparotomy, adhesiolysis, and gastrojejunostomy to bypass the pancreatic head mass. Administration of oral levothyroxine were attempted after surgery; however, she had recurrent vomiting and required prolonged nothing per orem and parenteral nutrition. Scout film of the abdomen showed ileus. Hypothyroidism was thought to be a contributing factor, as the patient had been unable to regularly take oral levothyroxine for over two weeks.

At this time, thyroid stimulating hormone (TSH) was elevated at 23.2 uIU/ml (0.35‐4.94 uIU/ml) with low normal free T4 0.7 ng/dl (0.70‐1.48 ng/dl). Rectal administration of levothyroxine was considered, but since the patient already had ileostomy, we decided to give levothyroxine solution via ileostomy. Levothyroxine solution was prepared by dissolving 300 mcg levothyroxine in 50ml of plain saline solution, four times her oral maintenance dose. It was given via ileostomy using a French 24 foley catheter and allowed to dwell for 2 hours. Levothyroxine dose was titrated daily depending on the free T4 level drawn 12 hours after every dose, with the steady‐state dose at 600 mcg daily by day 6 (free T4 1.2 ng/dl). She was given levothyroxine by ileostomy for a total of 7 days, after which oral levothyroxine was resumed after resolution of vomiting. She later succumbed to recurrent infections and complications from metastatic cancer.

Managing hypothyroidism in this patient was challenging because she was unable to take oral levothyroxine due to recurrent vomiting despite surgical therapy. An estimated 40‐80% of oral levothyroxine is absorbed from the jejunum and upper ileum. Since she already had an ileostomy access, we delivered the levothyroxine solution via ileostomy. We were able to achieve normal free T4 levels at a dose of 6 to 13 μg per kg/day, which is four to eight times the full replacement oral dose, versus over ten times the oral dose required for rectal administration in previous case reports. In patients in whom this route is available, ileostomy is an alternative means of levothyroxine administration among patients who cannot use the oral route.

POSTER 468

Thyroid Hormone Action Metabolism and Regulation Clinical Poster

SENSITIVITY TO THYROID HORMONES WITH SERUM URIC ACID LEVELS IN EUTHYROID ADULTS: RESULTS FROM SURVEYS IN THE USA AND CHINA

Genfeng Yu, Qintao Ma, Heng Wan, Jie Shen*

Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), China

Background Association between thyroid hormones sensitivity index and uric acid (UA) has yet to be assessed in different populations. The aim of this study was to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, thyroid feedback quantile‐based index by FT4 (TFQI_FT4), thyroid feedback quantile‐based index by FT3 (TFQI_FT3), thyroid‐stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with serum uric acid (SUA) using two large data sets from the USA and China.

Methods 5557 and 8972 euthyroid adults in US NHANES and China SPEED‐Shunde respectively were included in this community‐based study. We calculated FT3/FT4 ratio (indicating peripheral thyroid hormone sensitivity), TFQI_FT3, TFQI_FT4, TSHI, and TT4RI (indicating central thyroid hormone sensitivity). The multivariable logistic/linear regression analysis, stratified analysis, and restricted cubic spline (RCS) analysis were conducted.

Results In US NHANES, compared with participants in quartile 1st (Q1), those in quartile 4th (Q4) of FT3/FT4 ratio (β 0.14, 95% CI (0.03, 0.26)) and TFQI_FT3 (β 0.23, 95% CI (0.11, 0.34)) had higher SUA. Compared with participants in quartile 1st (Q1), No associations of TFQI_FT4, TSHI, and TT4RI with SUA were found. In China SPEED‐Shunde, compared with participants in Q1, those in Q4 of FT3/FT4 ratio, TFQI_FT3, TFQI_FT4, TSHI, and TT4RI had higher UA (all P value <0.05). The results of FT3/FT4 ratio, TFQI_FT3, and TFQI_FT4 remained significant by logistic analysis (all P value <0.05). The associations of the FT3/FT4 ratio and TFQI_FT3 with SUA were generally consistent across the subgroups of age in both populations (all P values <0.05).

Conclusions Associations between TFQI_FT4 and hyperuricemia were significant in Chinese euthyroid adults, while not in US, confirming the need for more prospective cohort studies on race‐specific manner. Furthermore, increased FT3/FT4 ratio and TFQI_FT3 were significantly associated with a higher prevalence of hyperuricemia in both populations. The possible predictive effect of FT3/FT4 ratio and TFQI_FT3 on hyperuricemia was suggested to be taken seriously.

POSTER 469

Thyroid Hormone Action Metabolism and Regulation Clinical Poster

A MACHINE LEARNING‐ASSISTED SYSTEM TO PREDICT THYROTOXICOSIS USING PATIENTS' HEART RATE MONITORING DATA

Kyubo Shin¹, Jongchan Kim¹, Jaemin Park¹, Jae Hoon Moon*^1,2

¹THYROSCOPE INC., Korea, Republic of,²Department of Internal Medicine, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Korea, Republic of

Background: Previous studies have shown a correlation between resting heart rate (HR) measured by wearable devices and serum free thyroxine concentration in patients with thyroid dysfunction. We have developed a machine learning (ML)‐assisted system that uses HR data collected from wearable devices to predict the occurrence of thyrotoxicosis in patients.

Methods: HR monitoring data were collected using a wearable device for a period of 4 months in 175 patients with Graves' disease. During this period, 3 or 4 thyroid function tests (TFTs) were performed on each patient at intervals of at least one month. The HR data collected during the 10 days prior to each TFT were paired with the corresponding TFT results, resulting in a total of 662 pairs of data. Our ML‐assisted system predicted thyrotoxicosis of a patient at a given time point based on their HR‐TFT data pair at another time point. Thyrotoxicosis was defined as a predicted free T4 level >1.78 ng/dL.

Results: Our ML‐assisted system divided the 662 TFT results into either normal or thyrotoxicosis. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of our system for predicting thyrotoxicosis were 85.15%, 85.03%, 50.59%, and 96.95%, respectively. When subclinical thyrotoxicosis was excluded from the analysis, the sensitivity, specificity, PPV, and NPV of our system for predicting thyrotoxicosis were 85.15%, 97.99%, 93.48%, and 95.11%, respectively. Our ML‐assisted system used the change in mean, relative standard deviation, skewness, and kurtosis of HR while sleeping, and the Jensen‐Shannon divergence of sleep HR and TFT distribution as major parameters for predicting thyrotoxicosis.

Conclusion: Our ML‐assisted system has shown reasonably accurate predictions of thyrotoxicosis in patients with thyroid dysfunction. The accuracy of the system could be improved by gathering more data. This predictive system has the potential to monitor patients' thyroid function status without the need for blood tests.

POSTER 470

Thyroid Imaging Case Study Poster

THYROID MASS INVASION INTO INTERNAL JUGULAR VEIN

Sakshi Sharma*, K. Romo, Qasim Iqbal

Ochsner Clinic Foundation, USA

Introduction: While microscopic vascular invasion may be seen in thyroid cancers, particularly in follicular and poorly differentiated thyroid cancer subtypes, invasion of thyroid mass into the internal jugular vein (IJV) is a rare complication. The following is a case of a man with a thyroid mass thrombus within the IJV.

Description of the Case: A 72‐ year‐old‐male with prostate cancer s/p prostatectomy and radiation, hypertension, hyperlipidemia, and hyperthyroidism presented with tremors and unintentional weight loss of 10 lbs in the past two weeks. Exam revealed tachycardia, goiter, fine tremor on outstretched hands, without exophthalmos. Labs notable for TSH <0.10 (nl 0.4‐4.0), fT4 2.18 (nl 0.71‐1.51), T3 338 (nl 60‐180 ng/dL), and TRAb 21 (nl 0.0‐1.75 IU/L). Thyroid US with multiple right lobe with small cystic, hypere and solid nodules, appearing predominantly solid and hyperechoic, as well as isoechoic to hypoechoic components in the left lobe. He was started on metoprolol 12.5 mg BID and methimazole 10 mg BID. While performing FNA biopsy, extension of the right lobe of thyroid was seen towards the IJV, with possible compression/encasement. CT Neck with contrast done for better visualization showed a tumor thrombus within the right IJV. Evaluated by vascular surgery who recommended US to assess right IJ compressibility, found to be non‐compressible and started on anticoagulation with apixaban. ENT recommended non‐urgent thyroidectomy, pending.

Discussion: Because invasion of IJV with a thyroid mass is extremely rare, little is known regarding treatment and intervention approaches that may decrease morbidity and mortality for these patients. Rarity of cases may be due to underdiagnosis, thus increasing awareness may be helpful in identifying thyroid mass cervical vein involvement. Additionally, perioperative evaluation of patency of cervical veins may be useful.

POSTER 471

Thyroid Imaging Clinical Poster

CHARACTERISTICS INCLUDING THYROID ULTRASONOGRAPHY OF 315 PATIENTS WITH PAINLESS THYROIDITIS: DO PATIENTS WHO SHOW HYPOECHOIC AREAS HAVE SPECIFIC CLINICAL CHARACTERISTICS?

Miho Fukushita*, Natsuko Watanabe, Hideyuki Imai, Shigenori Hiruma, Nami Suzuki, Masako Matsumoto, Ai Yoshihara, Jaeduk Noh, Kiminori Sugino, Koichi Ito

Ito hospital, Japan

Background: Some patients with painless thyroiditis show irregularly shaped hypoechoic lesions on thyroid ultrasonography.

Objective: The characteristics of patients with painless thyroiditis and irregularly shaped hypoechoic ultrasonography were investigated.

Subjects and Methods: A total of 315 patients with painless thyroiditis who presented with thyrotoxicosis and no tenderness or pain in the neck to our hospital in 2021 were retrospectively evaluated. They were divided into two groups: one showed hypoechoic lesions (HE group: 14 patients, 4.4%); and the other showed no hypoechoic lesions (N group: 301 patients, 95.6%).

Results: The mean age (range) of the HE and N groups was 54 (21‐79) years and 36 (10‐79) years (p = 0.005), and the sex ratio (F:M) was 3:4 and 1:5.8 (p = 0.01), respectively; 7 (50.0%) and 201 (66.8%; p = 0.19) patients were positive for anti‐thyroglobulin antibodies, and 4 (28.6%) and 104 (33.6%; p = 0.65) patients were positive for anti‐thyroid peroxidase antibody, respectively. The HE group tended to include more male and elderly patients than the N group. In patients whose thyroid volume could be measured, there was no significant difference between the two groups: 19.6 (range 11.7‐51) ml in the HE group (11 patients) and 21.1 (3.8‐70.6) ml in the N group (292 patients). Final thyroid function showed no significant difference in the two groups, excluding patients who wanted to become pregnant and whose thyroid function was checked for less than 60 days; in the HE group, 11 patients recovered to within the reference interval (RI) (92.3%), and one patient showed subclinical hypothyroidism (7.7%), and in the N group, 178 patients recovered to within the RI (89%), and 22 patients showed hypothyroidism and subclinical hypothyroidism (7.7%). In the HE group, the hypoechoic lesion was present in both thyroid lobes in 7 patients and in the lateral lobe in 7 patients.

Conclusion: Irregularly shaped hypoechoic lesions were observed in 4.4% of patients with painless thyroiditis and were more common in male and elderly patients. Final thyroid function recovered to the RIs in about 90% of patients, with no difference between the HE and N groups.

POSTER 472

Thyroid Nodules and Goiter Basic Poster

THYROID NODULES ON THE RISE: UNDERSTANDING PREVALENCE AND RISK FACTORS IN PRIMARY CARE PATIENTS

Harshavardhini Kommavarapu*, Srinidhi Manchiraju, Jaime Nix, Oco Montoya, Tejasvi Pamganamamula, Gowtham Dronavalli, Madhu Pamganamamula

Center for Hypertension and Internal Medicine, USA

INTRODUCTION: Most thyroid nodules go undetected during routine clinical examination via palpation, especially in high BMI patients. This combined with their indolent nature, hinders their early detection. While most nodules are benign, there is always a concern for malignancy, warranting thorough screening criteria for thyroid nodules.

OBJECTIVE: To evaluate the prevalence of thyroid nodules in a diverse patient population, to determine their relationship with BMI, and to identify other risk factors to aid in the screening.

METHODS: A cross‐sectional study was conducted to detect the incidence and the number of thyroid nodules using ultrasonography among 1145 subjects attending a primary care clinic. The findings were evaluated for relationships with BMI, age, gender, free serum T3 levels, free serum T4 levels, and serum TSH levels as independent risk factors. Those with nodules sized >1.5 cm were referred for fine needle aspiration cytology (FNAC) and their results were analyzed to detect malignancy. The study used appropriate statistical analysis methods such as the chi‐square analysis and logistic regression to compare the findings within the various groups.

RESULTS: Thyroid nodules were detected in 552 individuals (48.2%), the average nodule size being 1 cm in either lobe and 0.89 cm in the isthmus of the gland.

37.5% underweight, 46.22% of normal, 50.55% overweight and 47.04% obese individuals had nodules. Chi‐square analysis did not reveal any significant association between BMI and the presence of nodules.

Females had a higher incidence (56.5%) than males (33.49%) (p < 0.001). Nodule prevalence increased with age, with the peak age group being 60‐80 years. Logistic regression analysis showed a statistically significant effect of age group on the presence of nodules (p < 0.05)

No significant relationship was detected between the incidence of nodules and any of the thyroid hormone levels. No specific risk factor was identifiable to result in an increased number or size of the nodules.

146 of 552 individuals with nodules had undergone FNAC with a malignancy being identified in only 3 individuals.

CONCLUSION: The study did not detect any significant association between BMI and the presence of thyroid nodules. It supports the concept that female gender and advancing age are important risk factors for the development of thyroid nodules. These factors should be considered in routine health check‐ups to promote timely detection and intervention. Further investigation into the influence of occupation, lifestyle, ethnicity, and medical history on the incidence of nodules may improve screening criteria and ultimately enhance patient outcomes.

POSTER 473

Thyroid Nodules and Goiter Case Study Poster

RECURRENCE OF THYROID NODULES AFTER TOTAL THYROIDECTOMY

Anusha Kothapalli, Issra Jamal*

UMass Chan Medical School‐Baystate, USA

Introduction: Total thyroidectomy is preferred to subtotal thyroidectomy for management of benign multinodular goiter since it has been demonstrated to be safe if performed by surgeons trained in the technique and is associated with lower rates of recurrence [1]. One study found that goiter can recur in up to 23% of those who underwent subtotal thyroidectomy, compared to 1 out of 3044 thyroid bed recurrences in those who underwent total thyroidectomy[1]. Recurrences can occur due to thyroid rests within embryological remnants, such as the thyrothymic tract or pyramidal lobe, which may not be identified as thyroid tissue and therefore may not be removed during surgery[1,2,3]. Another rare etiology proposed is intrathoracic ectopic thyroid tissue.

Case Presentation: A 35‐year‐old female initially presented to endocrinology for incidental finding of suppressed TSH on labs. Thyroid ultrasound and uptake scan confirmed toxic multinodular goiter. Given compressive symptoms, goiter size and hyperthyroidism patient was rendered euthyroid with methimazole followed by total thyroidectomy. Postoperative pathology noted nodular follicular hyperplasia and lymphocytic thyroiditis. Eight years later, neck CT after MVA incidentally revealed two nodules in the thyroidectomy bed described as complex nodules on outside neck US. Hence, she returned to endocrinology for further workup. Neck ultrasound noted right mid 1.58x1.52x2.10cm complex appearing nodule with intranodular vascularity and small area of echogenic foci as well as left mid 1.89x1.60x2.81cm complex appearing nodule , without calcifications. FNA biopsy was performed and the results were consistent with benign follicular thyroid nodules. Patient denied compressive symptoms so it was decided to follow up the nodules routinely.

Discussion: Even after total thyroidectomy, for a few reasons, the possibility of thyroid nodule recurrence remains. In the instances where nodules recur after total thyroidectomy, it is typically due to embryologic tissue remnants that were not removed during surgery, therefore to reduce the risk of recurrence of nodules post‐thyroidectomy it is important to be aware of the potential presence of these remnants and how to accurately identify them in order to completely remove them. There is some evidence that the thyrothymic tract may be the most difficult embryologic remnant to identify and completely remove. Post thyroidectomy, ultrasound surveillance when indicated can be a helpful tool to identify and appropriately risk stratify any nodules that may arise after total thyroidectomy.

POSTER 474

Thyroid Nodules and Goiter Case Study Poster

NOW YOU SEE ME, NOW YOU DON'T: COMPLETE RESOLUTION OF A SUSPICIOUS THYROID NODULE AFTER IMMUNOTHERAPY FOR UTERINE CANCER

Megan Parmer*, Gustavo Romero‐Velez, Allan Siperstein

Cleveland Clinic Foundation, USA

We present the case of a suspicious thyroid nodule that completely resolved while being treated with Pembrolizumab and Lenvatinib immunotherapy for metastatic uterine cancer. The patient is a female in her mid‐50s with stage IVB uterine serous carcinoma who underwent oncologic resection then carboplatin and paclitaxel therapy followed by bevacizumab, but had progression of disease. In the workup of her disease progression, she was found to have a left thyroid nodule which was later incidentally noted to be FDG‐PET avid. Thyroid ultrasound and biopsy at that time revealed a 1cm hypoechoic nodule with pathology demonstrating atypia of undetermined significance and Afirma genomic sequencing classifier was suspicious indicating at least a 50% chance of malignancy. The patient elected for serial ultrasound monitoring. Then, she started Pembrolizumab and Lenvatinib immunotherapy for her uterine cancer over the next 4 months. She was intermittently on levothyroxine during this time for hypothyroidism. Repeat ultrasound six months and again 1 year after biopsy demonstrated an atrophic thyroid and complete resolution of the left thyroid nodule. Given the timeline, we presume that the combination immunotherapy with Pembrolizumab and Lenvatinib lead to complete resolution of her suspicious nodule. Lenvatinib therapy is known to increase progression free survival in patients with metastatic radioactive iodine resistant disease despite its poor tolerance, however, it rarely causes resolution of disease. Pembrolizumab is known to cause adverse effects on the thyroid, including hypothyroidism. It is unclear which, if either, of these immunotherapies were responsible for complete resolution of the suspicious nodule or could have any treatment potential in the future for malignant thyroid nodules.

POSTER 475

Thyroid Nodules and Goiter Case Study Poster

A NOVEL DICER1 MUTATION IDENTIFIED IN A MALE WITH MULTINODULAR GOITER: A CASE REPORT

Amjad Ali*, Sarah Chaaban

Rainbow Babies and Children's Hospital, USA

Introduction: DICER1 syndrome is an autosomal dominant condition with reduced penetrance, characterized by cancer predisposition with thyroid manifestations of early onset multinodular goiter and differentiated thyroid cancer. We report a novel pathogenic DICER1 mutation (c.5528‐2del) in a family with multinodular goiter.

Case discussion: DICER1 mutation was suspected when a male patient presented with multinodular goiter incidentally noted on physical exam at 13 years of age. A thyroid ultrasound showed 5 isoechoic or hyperechoic solid and complex nodules. FNA with biopsy was suggestive of benign follicular nodules. Upon follow up, noted to have rapid interval growth of nodules. Genetic testing revealed a novel monoallelic mutation in the DICER1 gene located at c.5528‐2del (splice site), expected to lead to a loss of protein function. Of note, his mother and grandmother had a history of thyroid nodules requiring thyroidectomy. Mother's pathology consistent colloid adenoma with pseudopapillary hyperplasia and focal papillary adenomatous hyperplasia. His 11‐year‐old sister also with history of multinodular goiter. Similar to her brother, all solid and complex nodules were isoechoic or hyperechoic, with FNA biopsy findings consistent with benign follicular lesions. Both mother and sister underwent genetic testing which revealed the same DICER1 mutation.

Screening for other conditions associated with DICER1 mutation was unremarkable. He subsequently underwent thyroidectomy. Pathology was consistent with multifocal follicular adenomas with papillary architecture.

Discussion: We report a novel pathogenic DICER1 mutation (c.5528‐2del) in a family with early onset multinodular goiter. Our case further supports that early onset, familial, or male multinodular goiter should prompt the consideration of the presence of DICER1 syndrome.

POSTER 476

Thyroid Nodules and Goiter Clinical Poster

TREATMENT OUTCOMES FOLLOWING RADIOFREQUENCY ABLATION TREATMENT OF HYPER‐FUNCTIONING TOXIC THYROID NODULES: A PROSPECTIVE CASE SERIES AND SYSTEMATIC META‐ANALYSIS

Alexandra LaForteza*¹, Peter Issa², Chad Issa², Mohamed Hussein¹, Mohamed Shama¹, Eman Toraih¹, Emad Kandil¹

¹Department of Surgery, Tulane University School of Medicine, USA,²Louisiana State University Health Sciences Center School of Medicine, USA

Objective: Hyper‐functioning toxic thyroid nodules are characterized by overproduction of thyroid stimulating hormone (TSH) leading to hyperthyroidism over time. Radio frequency ablation (RFA) has previously been introduced to treat benign thyroid nodules. Due to efficacy and tolerability, this technique has become a new treatment in reducing the size of nodules and normalizing thyroid hormone levels in hyper functioning toxic nodules. Although this technique is promising, few North American works report the benefits of RFA for toxic nodules. This study aimed to evaluate the efficacy of RFA as a treatment option for hyper‐functioning toxic thyroid nodules.

Methods: Case series patients pre‐operative and post‐operative data were collected for each patient treated with RFA and followed up for 3 months to one year. The systematic meta‐analysis includes relevant studies published through March 2022 that met the following inclusion criteria: (1) Patients were diagnosed with hyperthyroidism with thyroid nodules and (2) patients underwent RFA for the treatment of hyper‐functioning thyroid nodules.

Results: The case series study included 8 hyper functioning toxic thyroid nodules treated with RFA. 7 of 8 patients who underwent RFA treatment experienced TSH normalization and discontinued medication. The mean TSH levels before RFA session was 0.047 ± 0.03 uIU/mL that increased to 1.89 ± 2.11 uIU/mL after ablation. The mean volume before RFA session was 13.05 ± 12.20 mL with a volume reduction rate (VRR) of 72.03% ± 22.32% at the final follow up period. The meta‐analysis, total of 14 studies including 426 thyroid nodules in 410 patients, concluded that the overall cure rate was 64% with increasing efficacy over the recent years and the total VRR of all toxic nodules was 72.86%.

Discussion: The results of our case series are consistent with the conclusions found in the meta‐analysis noting that RFA treatment of hyper‐functioning toxic nodules shows successful outcomes with normalizing TSH levels and reducing the size of the nodules. This study suggests that RFA may be an effective and safe treatment for toxic thyroid nodules for those who select against surgery. Further research of long‐term outcomes is needed for it to become a standard treatment.

POSTER 477

Thyroid Nodules and Goiter Clinical Poster

SERUM THYROXINE AS A PREDICTIVE FACTOR FOR DIFFERENTIATED THYROID CARCINOMA AND MALIGNANT NODULE CYTOLOGY AND ASSOCIATION TO INSULIN RESISTANCE FACTORS

Lina Celescuekci¹, Mariana Pinto¹, Ilka Mara Botelho², Elizabeth Pavin², Denise Zantut‐Wittmann*²

¹Faculty of Medicine, Pontifical Catholic University of Campinas, Brazil,²Division of Endocrinology, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Brazil

In recent years, there has been a significant increase in the number of thyroid cancer diagnosis and factors related to cardiovascular risk and insulin sensitivity, such as greater waist circumference, high concentrations of triglycerides and glycated hemoglobin, and high Homeostases Model Assessment‐Insulin Resistance Index (HOMA‐IR), seem to have a relationship with this increase, but there is still a lack of studies to corroborate these hypotheses.

Aims: This cross‐sectional study evaluated the relationship between ultrasonographic, clinical, cytological and anatomopathological characteristics of thyroid nodules with factors indicative of cardiovascular risk, changes in lipid and glucose profiles through medical records and interviews during routine medical consultation.

Results: The study included 160 patients with thyroid nodule, 85.53% women, 41.3% with obesity, 24.18% with type 2 Diabetes Mellitus, 63.4% hypertensive, 9.15% with a previous cardiovascular disease, 38.16% with dyslipidemia. Of these, 38.5% had Papillary Thyroid Carcinoma and 8.5%, Follicular Carcinoma. Regarding cytology, 34.64% of these patients had Bethesda II, 8.5% Bethesda III, 11.11% Bethesda IV, 26.8% Bethesda V, 8.5% Bethesda VI. Microcalcifications were associated with higher values of Framingham and ASCVD Cardiovascular Risk Scores, fasting glucose, and glycated hemoglobin. Nodules cytology Bethesda II had lower fasting glucose; Bethesda III greater glycated hemoglobin; and Bethesda IV, higher values on both cardiovascular risk scores. Framingham Score was lower in patients with papillary carcinoma, as well as the abdominal waist was lower in follicular thyroid carcinoma. Univariate logistic regression analysis showed that higher FT4 increased the chance of malignant cytology by 4.7 times In multivariate logistic regression analysis, higher HDL was a predictive factor for malignant cytology (OR = 1.064) and higher serum FT4, for Differentiated Thyroid Carcinoma (OR = 7.409).

In conclusion, nodules with higher malignancy potential on ultrasound were associated with increased Cardiovascular Risk and altered glucose metabolism, as well as larger and multiple nodules and goiters were related to factors indicative of insulin resistance. Malignant, and potentially malignant nodules seem to be related to hormonal factors that induce greater cell replication, such as thyroxine and insulin resistance and also, changes in glucose metabolism, however these findings report additional studies for due evidence.