Abstract
Background:
Surgical management of symptomatic benign thyroid nodules in patients with previous lobectomy poses a dilemma for physicians. Radiofrequency (RF) ablation may provide a treatment option that avoids surgery and preserves thyroid function. We evaluated whether RF ablation of benign thyroid nodules affects thyroid function in patients with previous lobectomy.
Methods:
A total of 11 patients with 14 thyroid nodules were enrolled using the following criteria: (i) having a predominantly solid nodule; (ii) reporting pressure symptoms or cosmetic problems; (iii) cytological confirmation of benignancy; (iv) no malignant features detected using ultrasound; (v) serum thyroid hormone and thyrotropin (TSH) levels within normal limits; and (vi) refusal of or ineligibility for surgery. Thyroid function, nodule volumes, and clinical concerns were evaluated before RF ablation and during follow-up after RF ablation.
Results:
The mean follow-up duration after RF ablation was 43.7±30.7 months (range=7–92 months). The mean nodule volume was 9.7 mL (0.9–57.6 mL) before the procedure, and was significantly decreased at the last follow-up (p<0.001) with a mean volume reduction rate of 87.2%. The mean symptom score (p=0.003) and cosmetic score (p=0.003) were both significantly decreased at the last follow-up. Levels of TSH, free thyroxine, and triiodothyronine were not significantly different prior to treatment and at the last follow-up (p>0.05), and remained normal in all patients.
Conclusions:
In patients with previous lobectomy, RF ablation should be considered as a first-line treatment for symptomatic benign thyroid nodules to preserve thyroid function.
Introduction
Several studies have suggested that RF ablation is an effective and safe alternative to surgery for treating benign thyroid nodules (2,7,11). Regarding thyroid function, transient hyperthyroidism has been reported in a few patients after RF ablation (2,12). Permanent hypothyroidism was reported in two studies: one from a large series of studies involving 1459 patients (13), and the other from a study of autonomously functioning thyroid nodules (8). However, the reason for permanent hypothyroidism was unclear owing to the elevated levels of antibodies against thyroid peroxidase (TPO) before ablation. Although thyroid function seems to be rarely influenced by RF ablation, we are not aware of any studies that investigated whether RF ablation affects thyroid function in patients with previous lobectomy.
The purpose of this study was to evaluate whether RF ablation for the treatment of benign thyroid nodules in patients with previous lobectomy affects thyroid function.
Materials and Methods
Patients
The protocol used in this retrospective study was approved by an Institutional Review Board that did not require either patient approval or informed consent for review of images and medical records. However, all patients undergoing ultrasound (US)-guided fine-needle aspiration and RF ablation provided written informed consent before each procedure.
Between June 2002 and December 2009, a total of 22 patients with previous lobectomy received RF ablation for the treatment of benign thyroid nodules. All patients had undergone prior lobectomies to treat benign thyroid nodules. Among them, seven patients were excluded because they were taking L-T4 after surgery because of hypothyroidism, and four patients were excluded because they were followed-up <6 months after RF ablation. A total of 11 patients with 14 thyroid nodules were finally included in this study (11 women; mean age=44.2 years; range=30–64 years). All enrolled patients fulfilled the following criteria: (i) having a thyroid nodule (solid portion >50%); (ii) reporting pressure symptoms or cosmetic problems; (iii) cytologic confirmation of benignancy at least twice, using US-guided fine-needle aspiration; (iv) no malignant features detected using US (14 –16); (v) serum thyroid hormone and thyrotropin (TSH) levels within normal limits; and (vi) refusal of or ineligibility for surgery. The relevant clinical data are summarized in Table 1.
Normal range of TSH is 0.4–4.0 mU/mL, whereas that of fT4 is 0.8–1.9 ng/dL and that of T3 is 61–173 ng/dL.
TSH, thyrotropin; fT4, free thyroxine; T3, triiodothyronine; TPO, thyroid peroxidase; Tg, thyroglobulin; NA, not applicable.
Preablation assessment, procedure, and follow-up
US examinations, fine-needle aspiration cytology, clinical concerns, and laboratory data were evaluated for all patients prior to RF ablation. The US and US-guided fine-needle aspiration examinations were performed by a radiologist (J.H.B.), using a 5–14 MHz linear probe fitted to a real-time US system (EUB-7500, Hitachi; iU-22, Philips; Aplio SSA-770A, Toshiba). The three orthogonal diameters of each nodule (the largest diameter and two other perpendicular diameters) were measured by US examination, and the volumes of nodules were calculated as Volume=π·a·b·c/6, where a is the largest diameter, and b and c are the other two perpendicular diameters. At enrollment, patients were asked to rate their symptoms on a 10-cm visual analog scale, ranging from 0 to 10 (17 –19). Physicians recorded a cosmetic score (1, no palpable mass; 2, no cosmetic problem but palpable mass; 3, a cosmetic problem on swallowing only; and 4, a readily detected cosmetic problem) (17 –19). The baseline protocol for laboratory data included assessment of TSH, free T4 (fT4), and triiodothyronine (T3). The presence of antibodies against TPO, thyroglobulin (Tg), and the TSH receptor was checked in 6 of 11 patients.
The RF ablation procedure was performed by the radiologist who performed the preablation assessments, using previously described techniques (2,7,11,17 –22). After skin sterilization and anesthesia with 2% lidocaine at the puncture site, an 18-gauge 1-cm active-tip internally cooled electrode was inserted into the nodule under US guidance, and the nodules were treated by using the moving-shot technique. During and after the procedure, complications were evaluated by monitoring for the appropriate clinical signs and symptoms, and the patients were discharged after 30 minutes of observation in the hospital (13,17,18).
After RF ablation, US examinations, clinical concerns, and laboratory data were followed up for all patients in the same manner as before RF ablation. The US examinations were performed at 1-month, 6-month, and last follow-up visits. Laboratory data and clinical concerns were evaluated after 6 months and last follow-up visits. We also evaluated any complications during the follow-up period.
Statistical analysis
Statistical analysis was performed using SPSS for Windows (version 14.0; SPSS Inc.). We compared the variables by use of Wilcoxon's signed rank test at enrollment and at the time of the last follow-up visit. The significance level was defined as p<0.05.
Results
The clinical data at the times of enrollment and the last follow-up are summarized in Table 2. The mean interval between surgery and RF ablation was 122.9±151.3 months (range=2–328 months). The mean follow-up duration after RF ablation was 43.7±30.7 months (range=7–92 months). After RF ablation, the mean nodule volume was significantly decreased at the last follow-up (p<0.001), with a mean volume reduction rate of 87.2%. The mean symptom score (p=0.003) and cosmetic score (p=0.003) were also significantly decreased at the last follow-up. Serum TSH, fT4, and T3 levels remained within normal limits in all patients, and mean serum levels were not changed significantly at the last follow-up (p>0.05).
Data are presented as mean±standard deviation (range).
Before RF ablation, four patients tested positive for thyroid antibodies. One patient was positive for both anti-TPO and anti-Tg antibodies, and three patients were positive for anti-Tg antibodies. The follow-up periods of these four patients were 36, 43, 69, and 92 months, respectively. After RF ablation, thyroid antibodies were still present in three of the patients, but had converted to negative in one patient. None of the patients were found to develop thyroid antibodies during the follow-up period.
We observed no major complications, such as voice change and hypoparathyroidism, after RF ablation throughout the follow-up period. None of the patients required surgery to address insufficient reductions of nodule volumes or clinical concerns after RF ablation.
Discussion
This study demonstrates that RF ablation does not affect thyroid function in patients with previous lobectomy during the mean follow-up period of 43.7 months. The absence of major complications, such as recurrent laryngeal nerve injury or hypoparathyroidism, indicates that RF ablation is a safe procedure, regardless of prior lobectomy. Regarding the efficacy of RF ablation, we achieved significant reductions in nodule volumes and improvement of clinical concerns, with no patients requiring additional surgery or other treatment.
Although surgery is a curative approach for treating thyroid nodules, permanent hypothyroidism is inevitable after total thyroidectomy (3,4). When symptomatic benign thyroid nodules develop in patients with previous lobectomy, the decision whether surgical management is the best treatment modality often poses a dilemma for physicians. The use of RAI therapy to treat autonomously functioning thyroid nodules may also cause hypothyroidism owing to its effects on the entire thyroid gland (5,6,8,23 –26). Nonsurgical treatments, such as RF, laser, and ethanol ablation, are thus attractive treatment options for preservation of thyroid function in these patients (10,19,27 –32). Unlike surgery or RAI therapy, damage to surrounding normal thyroid gland can be minimized because the efficacy of nonsurgical treatment is usually confined to targeted nodules. In our study, we treated one patient with four nodules in the remnant thyroid gland. Thyroid function in this individual was well preserved throughout the 92-month follow-up period.
There have been few reported cases of hypothyroidism after nonsurgical treatment of benign thyroid nodules. Regarding RF ablation, two cases of hypothyroidism have been reported (8,13). Of the two, one patient was treated for an autonomously functioning thyroid nodule, and both patients showed persistent elevation of serum thyroid antibodies before and after RF ablation. Regarding laser ablation, two patients with cold thyroid nodules developed hypothyroidism between 1 and 6 months after treatment (10). Both patients also showed persistent elevation of serum thyroid antibodies before and after RF ablation. Regarding ethanol ablation, hypothyroidism has been reported more commonly than either RF or laser ablation. The majority of these cases resulted from ethanol ablation of autonomously functioning thyroid nodules (5,6,23 –26). In a study where patients with previous thyroid surgery received ethanol ablation, 3 of 12 patients became hypothyroid: one with a toxic nodule and two with nontoxic solid nodules (33). The causes of hypothyroidism were ascribed to previous bilateral subtotal thyroidectomy and/or RAI therapy prior to ethanol ablation.
The cause of hypothyroidism arising after nonsurgical treatment of thyroid nodules is unclear, but previous studies suggest some general trends. Most patients had thyroid antibodies before treatment (5,6,8,13,24 –26), and some developed thyroid antibodies after treatment (6,34). When considering these trends, the main cause of hypothyroidism seems to be a progression of autoimmune thyroiditis associated with preexisting thyroid antibodies (24). Several studies reported the development of thyroid antibodies after laser ablation and ethanol ablation (6,34). Monzani et al. hypothesized that this phenomenon was related to elevation in levels of antibodies to Tg and to the release of denatured Tg into the bloodstream after ethanol ablation (6,35). However, development of anti-Tg antibodies is rarely reported, and is estimated to occur at a frequency of only 0%–1% after 1–3 years of follow-up (23). In our study, no patients developed thyroid antibodies after RF ablation. In addition, patients with newly developed thyroid antibodies did not develop hypothyroidism in studies that investigated the effects of ethanol and laser ablation (6,34). These results suggest a low probability of immunological activation and subsequent late hypothyroidism after nonsurgical treatment (23). Therefore, although the risk of hypothyroidism is very low after nonsurgical treatment of thyroid nodules, it may be prudent to warn patients with thyroid antibodies before treatment about the possibility of hypothyroidism (8,13).
Our study has several limitations, including its retrospective design and the small number of patients involved. However, because RF ablation of benign thyroid nodules is currently uncommon in patients with previous lobectomy, our preliminary findings may have a larger impact if they motivate more extensive prospective studies to assess the role of RF ablation in the management of symptomatic thyroid nodules in patients with previous lobectomy.
In conclusion, in patients with previous lobectomy, RF ablation has advantages over surgery or RAI therapy for the treatment of benign thyroid nodules in terms of maintaining thyroid function. To preserve thyroid function, RF ablation should be considered as a first-line treatment for selected patients.
Footnotes
Disclosure Statement
There is no conflict of interest to be disclosed for any of the authors regarding this article.