Stimulated Thyroglobulin and Neck Ultrasonography Facilitates Postsurgical Radioactive Iodine Remnant Ablation Selection in Patients with Low-Risk Well-Differentiated Thyroid Carcinoma

Dear Editor:

We read with great interest the article by Rosario et al. (1), which concluded that a stimulated thyroglobulin (Stim-Tg) <1 ng/mL combined with neck ultrasonography can be used to obviate the need for radioactive iodine remnant ablation (RRA) after a total thyroidectomy in low-risk well-differentiated thyroid carcinoma (WDTC) patients who do not have anti-Tg antibody interference. Based upon their retrospective analysis of a cohort of patients with low-risk WDTC, the authors have rightly concluded that a Stim-Tg of <1 ng/mL combined with negative high-resolution neck ultrasonography after a total thyroidectomy has a negative predictive value (NPV) for residual thyroid carcinoma of almost 100%. We applaud this approach and would like to emphasize that using a prospective strategy for low-risk WDTC, we obtained a postsurgical Stim-Tg of <1 ng/mL (∼3 months after initial total thyroidectomy) in 56.7% of our cohort (2), which is virtually identical to their 56% (1). This protocol, in the hands of experienced surgeons, translates into a 60% (1,2) decrease in RRA administration in low-risk WDTC patients after total thyroidectomy without prophylactic central and lateral neck dissections. Nascimento et al. (3) have also retrospectively concluded that RRA may be avoided in low-risk WDTC when a postsurgical Stim-Tg <1 ng/mL was obtained in the absence of detectable lymph nodes and aggressive histological variants of WDTC. However, their proposal differs from Rosario's (1) and ours (2) in that patients underwent routine prophylactic central and lateral neck compartment dissections while only achieving a 30% reduction in RRA administration for WDTC tumors that were <2 cm (4).

Rosario et al. have also proposed a strategy that administers a 30-mCi RRA dose for those low-risk WDTC patients who have a Stim-Tg value between 1 and 10 ng/mL (1). Since a weakly positive Stim-Tg after a total thyroidectomy could also represent a small residuum of normal tissue rather than thyroid carcinoma, we have deferred RRA for the majority of low-risk WDTC with a postsurgical Stim-Tg value between 1 and 5 ng/mL in favor of serial follow-up with repeat Stim-Tg and neck ultrasonography (2). Our follow-up of such a cohort who did not receive RRA for ∼4.7 years has shown that 97% of patients remained stable with no evidence of increasing Stim-Tg to >5 ng/mL, no significant increase in thyrotropin-basal ultrasensitive Tg, and no detectable abnormalities by neck ultrasonography (unpublished). Including these patients with a Stim-Tg <5 ng/mL to those with a Stim-Tg <1 ng/mL has resulted in nearly 85% of patients with low-risk WDTC avoiding RRA administration over several years of prospective follow-up (2).

Current RRA guidelines by the American Thyroid Association and other thyroid societies have not appreciated the high NPV of objective postsurgical Stim-Tg and neck ultrasonography to assist in RRA selection among low-risk WDTC patients. Instead, recommendations are based upon clinico-pathological variables such as patient age, tumor size, and presence of lymph node metastases, which result in a much higher RRA administration rate. However, our center has previously documented that patient age and tumor size do not reliably predict whether low-risk WDTC patients develop residual/recurrent disease when followed by Stim-Tg and neck ultrasonography (2). In our strategy, which includes surgery by expert surgeons, patients can be free of disease regardless of TNM staging without RRA as determined by long-term follow-up Stim-Tg and neck ultrasonography.

Early detection of low-risk thyroid cancer by thyroid ultrasonography and fine-needle aspiration biopsy in conjunction with a total thyroidectomy and therapeutic central compartment neck dissection (when indicated) has resulted in ∼60% of all detectable WDTC being of low risk (confined to the thyroid gland and/or minimal central compartment positive lymph nodes). The avoidance of RRA in ∼30%–60% (1 –3) of low-risk WDTC patients with a Stim-Tg <1 ng/mL and 85% with a Stim-Tg <5 ng/mL (2) will have a great impact on avoiding unnecessary RRA and merits consideration for future guidelines on the management of WDTC.