Autonomously Functioning Thyroid Nodules Research Articles

Radioiodine versus radiofrequency ablation to treat autonomously functioning thyroid nodules: a systematic review and comparative meta-analysis.

Radioiodine (RAI) is a well-established first-line therapy for autonomously functioning thyroid nodules (AFTN). Radiofrequency ablation (RFA) is a minimally invasive procedure that has been proposed as an alternative treatment option for hyperthyroidism caused by AFTN. Although RFA has been shown to be useful for reducing nodule volume and improving TSH levels in AFTN, no comprehensive comparative clinical studies have been proposed to evaluate the overall response to RFA treatment. The aim of this comparative systematic review and meta-analysis was to evaluate the response of RAI and RFA treatments in AFTN. A systematic search strategy was applied in PubMed, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov until July 2023 without time or language restrictions. Studies investigating the response to RAI and/or RFA treatment in AFTN patients 6 and/or 12months after treatment were included. The risk of bias was assessed based on the study design. Random-effect models were used for the meta-analysis. Twenty-three articles (28 reports) met the inclusion criteria and were included in the study. Overall, RAI therapy was found to have a significantly higher treatment response (94%) than RFA (59%), although the volume of AFTNs was reduced to a similar extent. In the direct comparison (n = 3 studies), RFA showed a higher risk of non-response than RAI (RR, 1.24; 95% CI, 0.94-1.63; z = 1.55; p = 0.12). Our results demonstrate the superiority of RAI over RFA in terms of success rates and safety profile and confirm RAI as the first choice for the treatment of AFTNs.

Autonomously functioning thyroid nodules present intermediate malignancy risk according to European Thyroid Imaging Reporting and Data System (EU-TIRADS) and yield indeterminate cytology results.

The aim was to evaluate the clinical, ultrasound (US) and, when indicated, the cytological and histological characteristics of autonomously functioning thyroid nodules (AFTN) in consecutive patients. A prospective, single-centre study was conducted between March 2018 and September 2021. In total, 901 consecutive patients were referred for thyroid workup and of 67 AFTN were evaluated. All enrolled patients underwent 99mTcO4 - scintigraphy, additional 123I scintigraphy only in case of normal serum TSH, evaluation of thyroid function, US examination using European Thyroid Imaging and Reporting Data System (EU-TIRADS), and US-guided fine needle aspiration (FNA) cytology when indicated. All indeterminate FNA samples were subjected to DNA sequencing analysis. More than half of the evaluated patients with AFTN were euthyroid; median serum TSH was 0.41 (IQR: 0.03-0.97) mU/L. The median AFTN size measured by US was 27.0 (IQR: 21.1-35.0) mm. 28.4% of AFTN were classified as EU-TIRADS score 3 and 71.6% as EU-TIRADS score 4, indicating that the majority of AFTN had intermediate risk for malignancy according to US. Out of the 47 AFTN subjected to cytological evaluation, 24 (51%) yielded indeterminate FNA results. DNA sequencing revealed pathogenic TSHR and GNAS mutations in 60% of cases. No malignancy was detected at final histology in surgically excised AFTN (n = 12). Of the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.

SAT470 Outcomes Of Radiofrequency Ablation For Autonomously Functioning Thyroid Adenoma- Mayo Clinic Experience

Abstract Disclosure: M. Dhanasekaran: None. A.A. Rajwani: None. M.R. Castro: None. J.C. Morris: None. J. Schmitz: None. R.A. Lee: None. M. Callstrom: None. M. Stan: None. Context: Autonomously functioning thyroid nodules (AFTNs) constitutes 5% of thyroid nodules and is the second most common cause of hyperthyroidism following Graves’ Disease. Untreated hyperthyroidism is associated with adverse cardiovascular and skeletal complications. Currently, radioactive iodine (RAI) and surgery are the standard treatment options for AFTNs, and both incur a risk of post-procedural hypothyroidism. To overcome this and other surgery/radiation-related complications, radiofrequency ablation (RFA) has been utilized in multiple countries (for both toxic and non-toxic thyroid nodules). It has been shown to induce significant nodule volume reduction along with restoration of normal thyroid function in many AFTNs. Methods: We present a single-center experience using RFA as an alternative treatment modality for AFTNs. The study's primary aim was to assess the efficacy of RFA in normalizing thyroid hormone concentration and restoring the euthyroid state. In addition, we analyzed the efficacy of RFA in nodule volume rate reduction (VRR) and its associated adverse events. Results: A total of 22 consecutive patients (17 F and 5 M) underwent RFA for a solitary AFTN (hot nodule in thyroid uptake and scan) under variable degrees of general anesthesia. 72% (n=16) had subclinical hyperthyroidism, 9% (n=2) had overt hyperthyroidism, and 18% (n=4) were biochemically euthyroid on anti-thyroid drugs (ATD). The mean age at the time of ablation was 52.09 years (SD= 14.6), with a mean BMI of 27.36 kg/m2 (SD= 4.67). Average pre-treatment TSH was 0.41 mIU/L (SD= 0.980) and free T4 1.29 ng/dl (SD= 0.33). The thyroid function was assessed after a single RFA session. TSH normalized in all patients within 3-6 months following the ablation. All four patients on ATD pre-treatment discontinued therapy within three months following the procedure. The average VRR (62.54%) was achieved within 3-6 months following the RFA, and importantly, none of the nodules grew back during the follow-up period (up to 24 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and two (9%) developed mild hypothyroidism requiring levothyroxine therapy. One patient, euthyroid post RFA, developed recurrent hyperthyroidism 45 months later and elected to undergo lobectomy. No serious adverse effects were noted in this cohort. Conclusions - RAI and/or surgery represent the standard of care for toxic adenomas but RFA shows excellent efficacy along with an excellent safety profile. Therefore at centers with RFA expertise it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications. Presentation Date: Saturday, June 17, 2023

Radiofrequency ablation for autonomously functioning nodules as treatment for hyperthyroidism: subgroup analysis of toxic adenoma and multinodular goitre and predictors for treatment success

PurposeTreatment of hyperthyroidism caused by autonomously functioning thyroid nodules (AFTN) with 131I often leads to undesirable hypothyroidism. Radiofrequency ablation (RFA) has emerged as a promising alternative. This retrospective analysis aimed to examine the efficacy of, and postprocedural hypothyroidism after, RFA for AFTN.MethodsPatients with hyperthyroidism caused by AFTN and treated with RFA were included if follow-up of at least 1 year was available. Cure was defined as thyroid medication–free biochemical euthyroidism. To predict cure, patient and treatment factors were analysed. A distinction was made between solitary toxic adenoma (STA) and toxic multinodular goitre (TMG).ResultsForty-eight patients (36 STA, 12 TMG) were included. One year post-RFA cure rate was 72% in STA versus 25% in TMG (p = 0.004). One patient developed hypothyroidism. In 11 patients that remained hyperthyroid, a second RFA was successful in 83% of STA and 40% of TMG patients. At last available follow-up, this amounted to a total cure rate of 81% in STA and 33% in TMG (p = 0.002). In STA, cured patients had a higher baseline TSH and a lower FT3 than non-cured patients (p = 0.026 and 0.031). Cure was observed in 91% of patients when > 2.1 kJ/mL was delivered during RFA, compared to 44% when less energy was administered.ConclusionThe efficacy of RFA was nearly 3 times higher in STA patients compared to TMG. Severity of hyperthyroidism and kJ/mL delivered during RFA predicts cure. Direct comparison to the current standard of care is needed to implement RFA in treatment of hyperthyroidism caused by AFTN.

Abstract #1407308: Marine Lenhart Syndrome: Case Series of Autonomously Functioning Thyroid Nodule with Graves’ Disease

Marine-Lenhart syndrome, first described in 1911 by Marine and Lenhart is the coincidence of Graves’ disease with autonomous functioning thyroid nodules. It is a very rare condition, but now considered a distinct sub entity of Graves’ disease. Here we represent case series of seven patients. This is a case series of seven patients presented with autonomous functioning thyroid nodules (AFTN) on background of Graves’ disease. All our patients were females with mean age of 44.5 years. Symptoms of hyperthyroidism were present in 5 of these patients, while other two were asymptomatic at time of presentation. Four of them had Grave’s opthalmopathy with predominant symptom of proptosis. Autoimmunity especially thyroid receptor antibodies were present in almost all of these patients. Thyroid function tests of five patients showed hyperthyroidism, one had subclinical hyperthyroidism and other one was hypothyroid at time of presentation with history of taking Radioactive iodine (RAI) for thyroid nodule few years back. Six of them were treated with antithyroid drugs, while 3 also received RAI as definitive treatment. One patient was on thyroxine as she was hypothyroid after receiving RAI few years back. Thyroid nodules, which occur in 10–15 % of patients with Graves’ disease, may present as pseudo-nodules, nodular goiter, hyperplastic nodules, differentiated thyroid cancer, or as AFTN. Presence of AFTN is quite rare, reported prevalence was 0.8–2.7 %. Treatment of these nodules may prove to be difficult due to the higher dose of RAI treatment needed compared with patients having Graves’ disease alone. Few cases have been reported so far but the most appropriate management approach needs to be determined.

Image-guided Thermal Ablation as a Promising Approach to Both Nontoxic and Toxic Autonomously Functioning Thyroid Nodules

Although thermal ablation has been recommended as an alternative therapy option for autonomously functioning thyroid nodules (AFTN), current clinical evidence mainly focuses on toxic AFTN. This study aims to evaluate and compare the efficacy and safety of thermal ablation (percutaneous radiofrequency ablation or microwave ablation) in treating nontoxic and toxic AFTN. AFTN patients who received a single session of thermal ablation with a follow-up period ≥12 months were recruited. Changes in nodule volume and thyroid function, and complications were evaluated. Technical efficacy was defined as the maintenance or restoration of euthyroidism with a volume reduction rate (VRR) ≥80% at the last follow-up. In total, 51 AFTN patients (age: 43.8±13.9 years, female: 88.2%) with a median follow-up period of 18.0 (12.0-24.0) months were included, where 31 were nontoxic (nontoxic group), and 20 were toxic (toxic group) before ablation. The median VRR was 96.3% (80.1%-98.5%) and 88.3% (78.3%-96.2%) in the nontoxic and toxic groups, respectively, and the respective euthyroidism rates were 93.5% (29/31, 2 evolved to toxic) and 75.0% (15/20, 5 remained toxic). The corresponding technical efficacy was 77.4% (24/31) and 55.0% (11/20, p=0.126). Except for one case of stress-induced cardiomyopathy in the toxic group, no permanent hypothyroidism or other major complications occurred in both groups. Image-guided thermal ablation is efficacious and safe in treating AFTN, both nontoxic and toxic. Recognition of nontoxic AFTN would be helpful for treatment, efficacy evaluation, and follow-up.

Study of technetium pertechnetate (99mTcO4) thyroid scintigraphy imaging among patients presenting with thyrotoxicosis at a tertiary care hospital in Kathmandu, Nepal

Background: Thyroid disorders represent an important public health problem worldwide. Excess thyroid hormone in the circulation due to any cause is termed as thyrotoxicosis. There are many causes of thyrotoxicosis, and it is important to find the cause as this will determine the management of the condition. 99mTcO4scintigraphy is diagnostic tool to differentiate various causes of thyrotoxicosis. This study aims to study the age and gender distribution of different causes of thyrotoxicosis.
 Methods: This is a retrospective analysis of technetium pertechnetate(99mTcO4) thyroid scintigraphy reports done of patients having thyrotoxicosis from the period of January 01, 2016, to December 31, 2016, at the Nuclear Medicine unit of National Academy of Medical Sciences, Bir Hospital, Kathmandu. Gender and age group analysis of the data was done using SPSS program.
 Results: A total of 211 reports of 99m TcO 4 thyroid scintigraphy were included in the study. There were 61 male patients and 150 female patients. Various causes of thyrotoxicosis like thyroiditis, Graves’ disease, autonomous functioning thyroid nodule, toxic multinodular goiter was detected. Apart from toxic multinodular goiter, these disorders were more common in the age group 18-50 years and females.
 Conclusion: 99mTcO4 thyroid scintigraphy is one of the easy and highly effective tools for the differential diagnosis of thyrotoxicosis. Both thyroiditis and Graves’ disease are more predominant in the age group 18-50 years and in females. Further large community-based studies will be required for exact prevalence of the diseases in the population.

LBSAT314 Diagnosis And Management Of A Rare Case Of Marine-Lenhart Syndrome

Abstract Introduction Marine-Lenhart syndrome is defined as Graves’ disease with co-existing toxic thyroid nodules. Approximately 25% to 30% of patients with Graves’ disease have accompanying nodules. More than 95% of these nodules are hypoactive, and thus, only a tiny percentage are hyperactive. In these patients, Graves’ disease and toxic nodules both contribute to thyrotoxicosis11. Here we present a case that details this syndrome's diagnosis, management, and treatment complication. Clinical Case A 68-year-old female presented to the primary care physician's office with complaints of anxiety and heat intolerance. Three years before this visit, the patient was diagnosed with Graves’ disease. She had achieved remission after one year of methimazole therapy. During the office visit, the patient was in sinus tachycardia at 112 BPM. There were no signs of exophthalmos on examination, and the thyroid was not palpable. Further testing revealed thyrotoxicosis with suppressed TSH of <0. 01 mcIU/mL (0.36-3.74) and elevated free T4 of 2.49 ng/dL (0.76-1.46). Thyrotropin receptor antibody (TRAb) was positive at 2.60 IU/L (0. 00-1.75). The patient was started on atenolol. Although TRAb was positive, thyroid ultrasound and radioactive iodine uptake scan (RAIU) were ordered to look for alternative diagnoses. The thyroid ultrasound showed four nodules in the left lobe, the largest of which was 1.8×1.5×1.3 cm. RAIU showed increased 24-hour uptake of 45% and three areas of increased focal uptake in the left thyroid lobe consistent with toxic nodules. Definitive treatment was needed due to both toxic nodules and Graves’ disease. The patient agreed to radioiodine ablation therapy (RAI) and received a dose of 21 uCi. One month after receiving RAI, the patient complained of worsening anxiety and heat intolerance. On repeat testing, TSH was <0. 01mcIU/mL, and free T4 was 4.78 ng/dL. The patient developed radiation thyroiditis and was given methimazole 10mg daily for two weeks. Three weeks after the course of methimazole, the patient became hypothyroid and was managed with 88 mcg of levothyroxine daily with no symptoms. Conclusion Common causes of hyperthyroidism are Graves’ disease or autonomous functioning thyroid nodules per the American Thyroid Association12. However, in hyperthyroid patients, Marine-Lenhart syndrome should be considered, especially those with thyrotoxicosis recurrence. This diagnosis steers management away from antithyroid drugs and toward RAI or thyroidectomy. For patients treated with RAI, antithyroid medications should be included as an adjunct therapy to reduce post-radiation thyroiditis. References 1 Cakir, Mehtap. "Marine-Lenhart Syndrome.," Journal of the National Medical Association 97, no. 7 (July 2005): 1036-38.12 Ross, Burch, et al., Thyroid. Oct 2016, 26(10): 1343-1421. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT275 A Rare Case of Thyroid-Stimulating Immunoglobulin-Induced Thyrotoxicosis in Poorly Differentiated Metastatic Thyroid Cancer

Abstract We report case of a rare of hyperthyroidism secondary to functional metastatic thyroid carcinoma, which is an infrequent phenomenon that can be challenging to diagnose and treat, as low thyroid-stimulating hormone (TSH) levels can suppress the development and growth of differentiated thyroid carcinoma cells. Previous studies have reported that hyperfunctioning thyroid carcinoma may present as autonomous functioning thyroid nodules (AFTN) within the thyroid gland, or as functioning lesions in metastatic foci, which is our case. Functional thyroid carcinomas are capable of absorbing iodine, as well as synthesizing and releasing thyroxine, are often associated with follicular thyroid carcinomas. Potential mechanisms for the thyrotoxicosis include a large aggregate tumor mass, as well as the presence of thyroid-stimulating immunoglobulins (TSIs) that are able to stimulate the thyroid-stimulating hormone (TSH) receptors of the thyroid carcinoma. In this clinical case, patient presented with high titers of TSIs, and metastatic thyroid carcinoma, with persistent hyperthyroidism after thyroidectomy and with a remarkable radioactive iodine treatment response. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The FDG Pattern of Autonomously Functioning Thyroid Nodules Correlates With Thyroid-Stimulating Hormone and Histopathology.

Whereas the 18 F-FDG PET/CT pattern of malignant thyroid neoplasia is known, the glucose uptake of autonomously functioning thyroid nodules (AFTNs) has not been fully investigated. We aimed to analyze the FDG uptake of AFTNs and its correlation with clinical, laboratory, ultrasonography, and histological features. We retrospectively analyzed the records of all AFTN patients from 2 centers, in which an 18 F-FDG PET/CT, thyroid function tests, and neck ultrasound were available within a 3-month window from the thyroid scintigraphy. Forty-five patients (35 female patients; median age, 65 years) were retrospectively included. The presence of FDG uptake was compared with the laboratory data and, whenever available, the histology. Over a 36-month follow-up, 20 patients underwent surgery; 4 cancers, 10 follicular adenomas, and 6 follicular hyperplasias were found. Twenty-two AFTNs (48.9%) were FDG-positive, whereas the remaining 23 (51.1%) were not. Thyroid-stimulating hormone (TSH) was significantly lower in FDG-positive AFTNs than in negative ones (0.055 [0.02-0.42] vs 0.65 [0.2-0.96] mIU/L, P = 0.0018). On multivariate analysis, only TSH was independently associated with FDG uptake ( P = 0.008). On receiver operating characteristic curve analysis, TSH <0.08 mIU/L indicated FDG-positive AFTNs, with 64% sensitivity, 87% specificity, 4.88 positive likelihood ratio, and 0.42 negative likelihood ratio. In histologically proven benign lesions, TSH was significantly lower in follicular adenomas than in follicular hyperplasias ( P < 0.001). Patients with cancer had TSH in the low-normal range. Autonomously functioning thyroid nodules show heterogeneous uptake FDG pattern, which depends on histopathology and thyroid function. Particularly, follicular adenomas tend to display increased glucose uptake and suppressed TSH.

Indications and extended follow-up of radiofrequency ablation for treatment of hyperthyroidism caused by solitary autonomous functioning thyroid nodules

Indications and extended follow-up of radiofrequency ablation for treatment of hyperthyroidism caused by solitary autonomous functioning thyroid nodules

Role of Thyroid RFA in the Treatment of Autonomously Functioning Thyroid Nodules

Autonomously functioning thyroid nodules (AFTN) are a common cause of hyperthyroid symptoms. While hemithyroidectomy or radioactive iodine ablation have historically been used to treat AFTNs, percutaneous thyroid radiofrequency ablation (RFA) is emerging as a promising option for outpatient therapy. The technique is compared to medical therapy, radioactive iodine therapy, and surgery, with an emphasis on technical differences in the ablation procedure for AFTN vs other benign thyroid nodules.

Autonomously functioning thyroid nodule: a patient-based review

Autonomously Functioning Thyroid Nodule (AFTN) is a rare cause of hyperthyroidism. AFTN, first described by Emil Goetsch in 1918, is the presence of a single hyperfunctioning thyroid nodule, which is not under the control of the pituitary/thyroid axis. The current theory on the development of hyperfunctioning nodules is the constitutive activation of Thyroid Stimulating Hormone Receptor (TSHR) due to a somatic point mutation and mutations of Gsa. The reported incidence of AFTN is about 1% on the investigation of thyroid nodules. Only about 10% - 30% become hyperfunction. Due to the rarity and lack of understanding of its characteristic clinical behaviour, AFTNs are often overlooked and undertreated. The ensuing review is based on a 36-year-old female who underwent left hemithyroidectomy for an AFTN and is well to date. There are two main issues in the diagnosis and management of AFTN. The first is that the diagnosis is not always made as most patients with AFTNs are functionally euthyroid. The other is the paucity of data in the literature to offer evidencebased individualized management for patients. As there are no tissue diagnostic criteria for AFTN; clinical, biochemical and radiological assessments to establish TSH independent nodular hyperfunction will clinch the diagnosis.Surgery and Radioiodine ablation remain the main forms of treatment for AFTN. Other methods such as percutaneous ethanol injection therapy (PEIT), laser ablation (LA), radiofrequency ablation (RFA) have a limited role in the management of an AFTN. The newer methods alluded to above will need further evaluation and a better definition of exact roles in the management of an AFTN.

Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3years. Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. A total of 361 patients (244 females, 117 males, median age 58years, IQR 46-70years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2months, in 38.9% at 6months, and in 41.3% at 12months. A significant difference in the rate of patients who withdrawn medical therapy at 12months was registered between small (< 10mL) (74%), medium (49%), or large (> 30mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Radiofrequency Ablation and Autonomous Functioning Thyroid Nodules: Review of the Current Literature.

Autonomously functioning thyroid nodules (AFTNs) have long been treated with either surgery or radioactive iodine (RAI). Being an invasive procedure, even thyroid lobectomy for this condition is associated with complications such as anesthesia side effects, scarring, iatrogenic hypothyroidism, and injury to other structures. Similarly, RAI is associated with hypothyroidism and may require multiple courses. Therefore, minimally invasive techniques such as radiofrequency ablation (RFA) are being advocated as an alternative treatment for AFTNs. To date, only few studies have been published on this topic and are largely on European and Asian populations. The aim of this review is to assess the efficacy and safety of RFA as a potential alternative for treatment of AFTNs compared to conventional surgery and radioiodine. Comprehensive PubMed and Embase searches were performed using the following terms such as (autonomously functioning thyroid nodules and radiofrequency ablation), (radiofrequency ablation and hyperthyroidism), and (radiofrequency ablation and toxic thyroid nodule). Both prospective and retrospective studies were included based on the inclusion and exclusion criteria specified in the text. Initially, 57 studies were identified and after excluding 47 studies, finally 10 studies were included in the review. Although surgery remains the first line treatment for AFTN. However, RFA is a safe option compared to RAI or surgery, especially in patients who are high-risk surgical candidates or have absolute contraindications to RAI. Currently, trials with follow-up greater than or equal to 5 years are warranted. It will aid in formulating a standardized surveillance protocol and also generalize RFA's use for AFTN. Laryngoscope, 132:906-914, 2022.

Impact of molecular testing on detecting mimics of oncocytic neoplasms in thyroid fine-needle aspirates diagnosed as follicular neoplasm of Hürthle cell (oncocytic) type.

Some thyroid nodules cytologically presenting as follicular neoplasm, Hürthle cell (Oncocytic) type (FNHCT), are not oncocytic tumors and represent autonomously functioning thyroid nodules (AFTNs) with TSHR, GNAS, and EZH1 mutations or oncocytic metaplasia. A to be defined subset of FNHCT harbors genome haploidisation-type DNA copy number alterations (GH-CNA). Molecular profiling of FNHCT may distinguish oncocytic neoplasms from its mimics. Consecutive fine-needle aspirates of 180 thyroid nodules over 37 months diagnosed as FNHCT and tested by ThyroSeq v3 were identified. Histologic follow-up was available for 79 of 180 nodules (44%). No molecular alterations were found in 76 of 180 nodules (42%), of which 15 were resected (oncocytic metaplasia, n = 7; follicular oncocytic adenoma, n = 8). Of nodules followed without surgery, 17 of 101 (17%) showed TSHR, EZH1, and GNAS mutations of AFTNs. Papillary thyroid carcinoma was identified by BRAF V600E (n = 2) and hyalinizing trabecular adenoma by PAX8-GLIS3 (n = 1). GH-CNA alone was detected in 42 of 180 FNHCT nodules (23%), of which 29 were resected and histologically diagnosed as follicular oncocytic neoplasms. All remaining resected nodules were histologically proven oncocytic neoplasms: 1) RAS-like alterations without GH-CNA (n = 25) and 2) TERT and/or TP53 mutations co-occurring with GH-CNA (n = 6), including anaplastic thyroid carcinoma arising from follicular oncocytic carcinoma with TP53, TERT mutations with GH-CNA (n = 2). A proportion of FNHCT nodules are AFTNs and oncocytic metaplasias, which can be suspected based on characteristic mutations or lack of alterations on molecular testing. Among resected FNHCTs, GH-CNAs characterize approximately half of histologically confirmed follicular oncocytic neoplasms.

Challenges in the functional diagnosis of thyroid nodules before surgery for TSH-producing pituitary adenoma.

SummaryA 50-year-old woman with thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma) was diagnosed due to symptoms of thyrotoxicosis. Preoperatively, she showed thyrotoxicosis with the syndrome of inappropriate secretion of TSH (SITSH) and had a 5 cm nodule in her thyroid gland. Octreotide was administered preoperatively, which helped lower her serum TSH level but not her thyroid hormone level. These findings were atypical for a patient with TSHoma. The TSHoma was completely resected, and the TSH level dropped below the sensitivity limit shortly after surgery. Interestingly, however, thyroid hormone levels remained high. A clear clue to the aetiology was provided by consecutive thyroid scintigraphy. Although preoperative thyroid scintigraphy did not show a hot nodule and the mass was thought to be a non-functional thyroid nodule, the nodule was found to be hot in the postoperative phase of TSH suppression. By focusing on the atypical postoperative course of the TSHoma, we were able to conclude that this was a case of TSHoma combined with an autonomously functioning thyroid nodule (AFTN).Learning pointsThe diagnosis of autonomously functioning thyroid nodules (AFTNs) depends on suppressed serum TSH levels.If thyroid hormones are resistant to somatostatin analogue therapy or surgery for TSHoma, complications of AFTN as well as destructive thyroiditis need to be considered.It is important to revisit the basics when facing diagnostic difficulties and not to give up on understanding the pathology.

Application and Utility of Radiofrequency Ablation in the Treatment of Benign Thyroid Nodules

Most thyroid nodules are benign and asymptomatic; however, some will ultimately cause compressive symptoms or develop autonomous function. Radiofrequency ablation (RFA) has emerged as a novel treatment option in lieu of other minimally invasive ablative techniques. This article discusses the role of RFA in the management of benign thyroid nodules and reviews recent literature comparing outcomes between RFA, surgery, and medical therapy. Multiple studies have demonstrated the safety and efficacy of RFA in the treatment of autonomously functioning thyroid nodules (AFTN) and symptomatic, cold nodules (SCN). The “moving shot” technique has proven successful in normalizing thyroid function for ATFNs and decreasing cosmetic/symptomatic concerns for SCNs after a single treatment. Radiofrequency ablation is a viable treatment option for the treatment of AFTNs and SCNs in patients who refuse or are otherwise unable to tolerate surgery. Patient selection is critical and performance at high-volume centers is necessary for best outcomes.

Ultrasound Assessment of Autonomous Thyroid Nodules before and after Radioiodine Therapy Using Thyroid Imaging Reporting and Data System (TIRADS).

The Thyroid Imaging and Reporting System (TIRADS) allows a sonographic assessment of the malignancy risk of thyroid nodules (TNs). To date, there is a lack of systematic data about the change in ultrasound (US) features after therapeutic interventions. The aim of this study was to characterize the changes in autonomously functioning thyroid nodules (AFTNs) after radioiodine therapy (RIT) by using TIRADS. We retrospectively assessed data from 68 patients with AFTNs treated with RIT between 2016 and 2018 who had available first and second follow-up US imaging. Before RIT, 69.1% of the AFTNs were classified as low-risk TNs when applying Kwak TIRADS (EU-TIRADS 52.9%), 22.1% were intermediate-risk TNs (EU-TIRADS 19.1%), and 8.8% were high-risk TNs (EU-TIRADS 27.9%). Twelve months after RIT, 22.1% of the AFTNs showed features of high-risk TNs according to Kwak TIRADS (EU-TIRADS 45.6%). The proportion of intermediate TNs also increased to 36.8% (EU-TIRADS 29.4%), and 41.2% were low-risk TNs (EU-TIRADS 25%). A significant percentage of AFTNs presented with features suspicious for malignancy according to TIRADS before RIT, and this number increased significantly after therapy. Therefore, before thyroid US, thorough anamnesis regarding prior radioiodine treatment is necessary to prevent unneeded diagnostic procedures.

Surgical perspective on radiofrequency ablation of thyroid tumors

: Radiofrequency ablation (RFA) is a safe and effective, minimally invasive procedure that has been used for decades to treat various tumors in the body. More recently, RFA has been applied to the head and neck, namely the thyroid. Part of its appeal is the lack of a cervical incision, general anesthetic, or removal of the thyroid gland at all, making it an easy office procedure for ablation of benign or malignant tumors. For enlarged benign tumors causing compressive symptoms, RFA can provide a safe option without enduring potential hypothyroidism, or the downtown associated with surgical recovery. For autonomously functioning thyroid nodules (AFTN), RFA may produce modest results for improving symptoms of hyperthyroidism as well as compression, thus expanding the existing options of radioactive iodine (RAI) and anti-thyroidal medications. For the treatment of primary or recurrent thyroid cancer, surgery is the standard of care. However, not all patients are eligible for surgery and in certain instances, revision thyroid surgery for recurrent cancer can pose significant risk to the patient. Thus, the option of a minimally invasive nonsurgical technique for ablation can improve their quality of life and provide clinicians with an extra tool in their armamentarium. We review the literature of this novel procedure and the role RFA can play in treating benign tumors (nonfunctioning and functioning), primary and recurrent thyroid cancers for patients that do not wish to have surgery or are ineligible.