Radiofrequency ablation (RFA) reduces the size of symptomatic thyroid nodules. Two benign fine needle aspirations (FNA) prior to RFA are recommended to rule out malignancy. Here we present a case of high-grade thyroid cancer found on subsequent surgical pathology despite 2 benign FNAs prior to RFA. A 31-year-old female presented with 5.5 cm American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TI-RADS) 3 nodule. Her family history and radiation exposure were negative. She opted for RFA and underwent FNA twice, which was benign. Her compressive symptoms recurred in 6 months. Ultrasound 13 months post-RFA demonstrated enlargement of the nodule to 6.0 cm, representing a 26% growth from the original size before therapy. The nodule remained at TI-RADS 3 based on ultrasound. Due to her compressive symptoms, she underwent a right hemithyroidectomy. Pathology showed a 6.5 cm differentiated high-grade thyroid carcinoma with oncocytic features, tumor necrosis, and extensive angioinvasion (pT3aN0a). She underwent completion thyroidectomy followed by radioactive iodine therapy (RAI). She achieved no evidence of disease status with undetectable thyroglobulin 9 months after the RAI. Ongoing follow-up after RFA is important to monitor for nodule regrowth and to recognize potential malignancy.

Background/Objective:The optimal period of a low-iodine diet (LID) during preparation for radioactive iodine therapy (RAI) is not well established. At the University of Washington, we conducted a retrospective analysis of patients with a diagnosis of differentiated thyroid cancers who underwent total thyroidectomy and RAI during the period 2022-2024 and compared urine iodine concentration in patients who had either 1 or 2 week of LID prior to RAI. Case Report:All analyses were performed using SAS software 9.4 (SAS Institute). There were 72 patients who met the criteria. The median age of this cohort was 46 years (range: 19-82) and 63.9% were female. Of these, 53 patients underwent a 1-week and 19 patients underwent a 2-week LID before RAI. The median value of urine iodine after a 2-week restriction was lower at 0.228 μmol/L (29 μg/L) (range: <0.079-1.481 μmol/L; <10-188 μg/L) compared to 1 week at 0.362 μmol/L (46 μg/L) (range: <0.079-30.43 μmol/L; <10-3863 μg/L), but not statistically significant (P = .24). Discussion:Although the urine iodine level was lower in 2-week restriction, there was no statistically significant difference between 1 versus 2-week iodine restrictions following RAI. This suggests that a 1-week LID may be adequate for RAI treatment. This would decrease time to treatment for patients and decrease the burden of LID. Conclusion:There is a need for future large prospective randomized control trials to identify the optimal duration of LID and determine the goal urinary iodine level for successful RAI ablation.

The NCCN Guidelines for Thyroid Carcinoma address the management of different types of thyroid carcinoma, including papillary, follicular, oncocytic, medullary, and anaplastic carcinoma. The NCCN Thyroid Carcinoma Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on the panel's most recent recommendations regarding systemic therapies for thyroid carcinoma as well as the supporting clinical data.

Cribriform morular thyroid carcinoma (CMTC) is a rare thyroid malignancy strongly associated with familial adenomatous polyposis (FAP). About 50% of CMTC cases are associated with FAP, including a subset in which CMTC is the presenting symptom in previously undiagnosed FAP. We present a case of a young woman with thyroid nodules monitored for several years due to low suspicion ultrasound features. After development of macrocalcifications in 1 nodule, she had a fine needle aspiration (FNA). The cytology was concerning for papillary thyroid carcinoma. She underwent total thyroidectomy with final pathology of CMTC. Given the strong association between CMTC and FAP, the patient completed endoscopy, colonoscopy, and genetic testing, which led to a diagnosis of FAP. The diagnosis of CMTC can be difficult because nodules are often small without concerning ultrasound features, not meeting recommendations for FNA. Due to an increased risk of CMTC in individuals with FAP, current criteria may be inadequate in identifying nodules warranting thyroid FNA. Continued ultrasound surveillance should be considered for nodules with low suspicion ultrasound features in this population.

Background: Remote-access thyroid and parathyroid surgery has emerged as a safe and effective alternative to conventional transcervical approaches, particularly valued for its superior cosmetic outcomes. However, global adoption remains inconsistent, hindered by variability in clinical indications, geographic and economic factors, learning curves, and training infrastructure. This international consensus statement aims to provide comprehensive, evidence-based guidance on patient selection, surgeon training, surgical approaches, and expected outcomes. An expert panel was convened with representatives nominated by six leading international societies The Asia-Pacific Society of Thyroid Surgery, American Head and Neck Society, American Association of Endocrine Surgeons, American Thyroid Association, European Society of Endocrine Surgeons, and Latin American Thyroid Society. A modified Delphi process, consistent with Conducting and Reporting of Delphi Studies guidelines, was used. Expert subgroups performed targeted literature reviews and formulated recommendations, which were refined through multiple rounds of anonymous electronic voting. Consensus was defined a priori as ≥80% agreement on a 5-point Likert scale. Summary: A total of 23 consensus statements were established. These include recommendations on minimum surgeon volume requirements, structured training pathways (including cadaveric dissection and proctoring), and patient eligibility based on disease characteristics. The four most commonly utilized remote-access approaches-transoral, gasless transaxillary, bilateral axillo-breast, and retroauricular-each offer distinct advantages and limitations. With an experienced surgeon, these techniques demonstrate oncologic and surgical outcomes comparable with open surgery, with notable improvements in cosmetic satisfaction. Approach-specific complications and extended operative times were acknowledged. The importance of informed consent and the development of high-volume centers of excellence was emphasized. Conclusions: This international consensus statement provides structured, evidence-informed recommendations to support the safe and effective implementation of remote-access thyroid and parathyroid surgery. Widespread dissemination and adoption of these recommendations may improve patient outcomes and promote global standardization of care.

Disclosure: S. Puri: None. M.Y. Roth: None. K. Madani: None. T.A. Tylee: None. M. Endo: None. Background: The Bethesda scoring system is a standardized risk assessment for malignancy based on features of thyroid FNA results. Categories range from I (nondiagnostic) to VI (malignant). This project aims to compare the presence of aggressive features of medullary thyroid cancer (MTC) between Bethesda categories. Methods: A cohort of patients at The University of Washington with a history of MTC was identified using Epic LEAF tool. Relevant data including Bethesda category, presence of lymph node metastases, cancer staging information, pre-op carcinoembryonic antigen (CEA) and calcitonin levels, and CEA and calcitonin levels at last follow up were extracted via chart review. Data was analyzed using JMP Pro 17. Wilcoxon two sample t-tests were performed, comparing data between Bethesda II/III/IV and V/VI groups. N=73 (Bethesda II=1, III=14, IV=3, V=10, VI=45). Results: Lymph node metastasis was significantly higher in Bethesda V/VI than II/III/IV [II/III/IV (N0 vs N1A vs N1B= 44% vs 11 vs 17%); V/VI (N0 vs N1A vs N1B= 20% vs 9 vs 60%)], (p=0.01). Structural disease was higher in Bethesda V/VI than II/III/IV (56% vs 27%), but not statistically significant (p=0.1). The presence of germline mutations was significantly higher in Bethesda V/VI [II/III/IV: 0% germline, 100% somatic; V/VI: 28% germline, 72% somatic (p=0.04)]. There was no statistically significant difference in tumor grading, metastases, lymphovascular invasion (LVI), and extrathyroidal extension (ETE) between Bethesda groups. Pre-op calcitonin was significantly higher in Bethesda V/VI [II/III/IV vs V/VI= 506 vs 1550, median value (p=0.02)]. There was no statistically significant difference in pre-op CEA levels, but these were higher in V/VI [II/III/IV vs V/VI= 20 vs 35, median value (p=0.39)]. CEA at the last follow-up was significantly higher in Bethesda V/VI [II/II/IV vs V/VI = 1.3 vs 6.5, median value (p=0.03)]. However, there was no statistically significant difference in calcitonin at last follow-up between Bethesda categories [II/III/VI vs V/VI= 8 vs 78, median value (p=0.09)]. Conclusion: Patients with Bethesda V/VI cytology tended to have more aggressive features of MTC such as lymph node metastases and higher tumor marker levels than those with II/III/VI cytology. Thus, initial FNA cytology may play a role in risk stratification and guiding future management of MTC. Presentation: Sunday, July 13, 2025

Objective:Case reports of postvaccine early-onset Graves' hyperthyroidism (PVGD) after the administration of COVID-19 vaccination have emerged. Our aim was to investigate whether the incidence of Graves' hyperthyroidism (GD) has increased after the introduction of COVID-19 vaccination. Methods:We compared the incidence of new-onset GD at a single academic center during 2 periods: December 2017 to October 2019 and December 2020 to October 2022, ie, before and after the implementation of COVID-19 vaccinations. We defined PVGD as laboratory-confirmed hyperthyroidism and GD within 4 weeks after the vaccination or clear onset of symptoms of thyrotoxicosis within 4 weeks of vaccination with evidence of hyperthyroidism and GD within 3 months. Results:During the prevaccination period, 803 patients carried diagnoses of GD, and of these, 131 were new. During the postvaccination period, 901 patients carried diagnoses of GD, and of these, 138 were new. There was no statistically significant difference in the incidence of GD (P = .52), age at onset, gender, or race between the 2 groups. Twenty-four of 138 newly diagnosed patients in the post-COVID-19 group met the criteria for PVGD. The median free T4 was higher, but this was not statistically significant (3.9 vs 2.5 ng/dL, P = .05). There were no differences in age, gender, race, antibody titers, or type of vaccination between PVGD and controls. Conclusion:There was no increase in new-onset GD after COVID-19 vaccination. Median free T4 was higher in patients with PVGD, but this was not statistically significant. & COPY; 2023 AACE. Published by Elsevier Inc. All rights reserved.

Clinical ThyroidologyVol. 34, No. 2 Thyroid CancerNewly Developed Pathologic Grading System Predicts Clinical Outcomes in Medullary Thyroid CarcinomaMayumi Endo, Eric C. Huang, and Mara Y. RothMayumi EndoDepartment of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, U.S.A.Search for more papers by this author, Eric C. HuangDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, U.S.A.Search for more papers by this author, and Mara Y. RothDepartment of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, U.S.A.Search for more papers by this authorPublished Online:14 Feb 2022https://doi.org/10.1089/ct.2022;34.89-91AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 34Issue 2Feb 2022 InformationCopyright 2022, Mary Ann Liebert, Inc.To cite this article:Mayumi Endo, Eric C. Huang, and Mara Y. Roth.Newly Developed Pathologic Grading System Predicts Clinical Outcomes in Medullary Thyroid Carcinoma.Clinical Thyroidology.Feb 2022.89-91.http://doi.org/10.1089/ct.2022;34.89-91Published in Volume: 34 Issue 2: February 14, 2022PDF download

Thyroglobulin (Tg), the substrate of thyroid hormone production, is a tumor marker used in the surveillance of differentiated thyroid cancer. Measurement by immunoassay has become increasingly sensitive, providing a window into the presence of residual and recurrent disease. However, testing is plagued by the challenge of Tg autoantibodies present in a substantial portion of the cancer population. Assays utilizing liquid chromatography-tandem mass spectrometry circumvent this problem but are not free from potential hurdles. Here, we review the current clinical application of Tg measurement, the challenge posed by anti-Tg antibodies to standard immunometric platforms, and the development of mass spectrometry-based approaches. Efforts to harmonize (or assess harmonization) of newer methods and further improve sensitivity are discussed, as well as clinical workflows for using mass spectrometry alongside standard immunoassay testing.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

Objective This work aims to guide clinicians practicing endocrinology in the use of telehealth (synchronous patient-clinician visits conducted over video or telephone) for outpatient care. Participants The Endocrine Society convened a 9-member panel of US endocrinologists with expertise in telehealth clinical care, telehealth operations, patient-centered care, health care delivery research, and/or evidence-based medicine. Evidence The panel conducted a literature search to identify studies published since 2000 about telehealth in endocrinology. One member extracted a list of factors affecting the quality of endocrine care via telehealth from the extant literature. The panel grouped these factors into 5 domains: clinical, patient, patient-clinician relationship, clinician, and health care setting and technology. Consensus Process For each domain, 2 or 3 members drew on existing literature and their expert opinions to draft a section examining the effect of the domain’s component factors on the appropriateness of telehealth use within endocrine practice. Appropriateness was evaluated in the context of the 6 Institute of Medicine aims for health care quality: patient-centeredness, equity, safety, effectiveness, timeliness, and efficiency. The panel held monthly virtual meetings to discuss and revise each domain. Two members wrote the remaining sections and integrated them with the domains to create the full policy perspective, which was reviewed and revised by all members. Conclusions Telehealth has become a common care modality within endocrinology. This policy perspective summarizes the factors determining telehealth appropriateness in various patient care scenarios. Strategies to increase the quality of telehealth care are offered. More research is needed to develop a robust evidence base for future guideline development.

Objective To determine the association between pathologic features and molecular classes (BRAF-like, RAS-like, and non-BRAF-like non-RAS-like [NBNR]). Methods Retrospective review of a merged database containing 676 patients, 84% (571/676) were assigned to a molecular class from publicly accessible sequenced data of thyroid neoplasms. Results The merged cohort included 571 neoplasms: 353 (62%) BRAF-like, 172 (30%) RAS-like, and 46 (8.1%) NBNR. Lymph node metastasis (any N1 disease) was present in 166/337 (49%) of BRAF-like, 23/164 (14%) of RAS-like, and 0/46 (0%) of NBNR and are significantly different (P < .001). Gross extra-thyroidal extension was observed in 27 patients, including 24/331 (7%) of BRAF-like, 2/160 (1%) of RAS-like, and 1/46 (2%) of NBNR (P = .01). N1B lymph node metastases or T4 disease was present in 74/333 (22%) of BRAF-like, 10/160 (6%) of RAS-like, and 1/46 (2%) of NBNR (P < .0001). Distant metastasis was present in 4/151 (2.6%) of BRAF-like, 2/50 (4%) of RAS-like and 0/46 for NBNR (P = .627). Angioinvasion was present in 0/81 (0%) of BRAF-like, 3/53 (6%) of RAS-like, and 3/46 (7%) of NBNR (P = .08); and multifocality was present in 27/81 (33%) of BRAF-like, 9/53 (17%) of RAS-like, and 1/46 (2%) for NBNR (P = .0001). Conclusion Pathological features of metastasis, gross extra-thyroidal extension, and multifocality were more prevalent in BRAF-like samples compared to RAS-like and NBNR. A trend towards increased frequency of angioinvasion in RAS-like and NBNR cancers compared to BRAF-like samples was observed. Further studies are needed to evaluate if preoperative knowledge of molecular mutations in thyroid tumors aids in decision-making regarding extent of surgery.

OBJECTIVE:To understand patient perspective regarding recommended changes in the 2015 American Thyroid Association (ATA) guidelines. Specifically, in regard to active surveillance (AS) of some small differentiated thyroid cancer (DTC), performance of less extensive surgery for low-risk DTC, and more selective administration of radioactive iodine (RAI).METHODS:An online survey was disseminated to thyroid cancer patient advocacy organizations and members of the ATA to distribute to the patients. Data were collected on demographic and treatment information, and patient experience with DTC. Patients were asked "what if" scenarios on core topics, including AS, extent of surgery, and indications for RAI.RESULTS:Survey responses were analyzed from 1546 patients with DTC: 1478 (96%) had a total thyroidectomy, and 1167 (76%) underwent RAI. If there was no change in the overall cancer outcome, 606 (39%) of respondents would have considered lobectomy over total thyroidectomy, 536 (35%) would have opted for AS, and 638 (41%) would have chosen to forego RAI. Moreover, (774/1217) 64% of respondents wanted more time with their clinicians when making decisions about the extent of surgery. A total of 621/1167 of patients experienced significant side effects with RAI, and 351/1167 of patients felt that the risks of treatment were not well explained. 1237/1546 (80%) of patients felt that AS would not be overly burdensome, and quality of life was the main reason cited for choosing AS.CONCLUSION:Patient perspective regarding choice in the management of low-risk DTC varies widely, and a large proportion of DTC patients would change aspects of their care if oncologic outcomes were equivalent.

OPINION STATEMENT:The landscape of treatment options for radioactive iodine refractory thyroid cancer is rapidly changing. While there are no curative options in this setting, tyrosine kinase inhibitors (TKIs) have revolutionized the management of radioiodine refractory disease to help delay progression of metastatic and life-threatening disease. Ongoing development of more selective targeted inhibitors will certainly improve medication tolerability and tumor specificity. In this review, we discuss the epidemiology of radioactive iodine refractory thyroid cancer and examine the definition of radioactive iodine refractory disease and the current systemic therapy options. We then discuss molecularly targeted strategies both approved by the FDA and currently under study in clinical trials. In particular, we examine the data relevant to specific targeted mutations in thyroid cancer. We also discuss novel approaches in development, such as immunotherapy, to the management of radioactive iodine refractory disease.

Abstract Adrenocortical carcinoma (ACC) is a rare malignancy that usually is detected as a result of symptoms of hormone excess or mass effect. We describe a rare presentation of ACC with primary aldosterone production leading to profound hypokalemia and cardiac arrest. The patient was previously asymptomatic with low-grade, untreated hypertension and no documented electrolyte abnormalities. She had sudden cardiac arrest, and potassium levels were undetectable. After successful resuscitation, imaging showed a 6-cm left adrenal mass highly suspicious for malignancy. Biochemical workup revealed aldosterone excess as well as cortisol excess, despite the absence of Cushingoid symptoms. Histopathological examination after surgical resection demonstrated high-grade ACC. This case illustrates that the workup of cardiac arrest as a result of electrolyte abnormalities should include evaluation for adrenal pathology.

BACKGROUND:Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone® (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical.OBJECTIVE:Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups.DESIGN:We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment.RESULTS:Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels.CONCLUSION:Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.

Thyroid nodules affect nearly two‐thirds of the world population. Fine‐needle biopsy with cytologic evaluation remains the diagnostic test of choice to distinguish benign from malignant thyroid nodules yet fails to discriminate as benign or malignant in up to one‐third of cases. This review discusses the limitation of current cytopathologic evaluation, the development of thyroid molecular testing, and the strengths and limitations of commercially available tests. Initial cytomolecular testing sought to identify specific gene mutations associated with thyroid cancer. Although the presence of a mutation was strongly associated with cancer, the likelihood of identifying a mutation was low; therefore, the test had low sensitivity. Subsequent tests developed have sought to improve the accuracy of cytomolecular testing for thyroid fine‐needle aspirations, both to reassure patients and providers when malignancy may be absent and to confirm the malignancy when present. The development of cytomolecular testing for thyroid nodules has informed and improved current understanding of thyroid nodule formation and progression. When used appropriately and with clear understanding of the advantages and disadvantages, cytomolecular testing has the potential to improve patient care in the setting of indeterminate thyroid nodules by helping to guide both the need for and the extent of thyroid surgery. Cancer 2018;124:888‐98. © 2017 American Cancer Society.

Measurement of intratesticular sex steroid concentrations in men informs both the development of male hormonal contraceptives and the understanding of male infertility. Given the challenges of using invasive techniques to measure testicular hormone physiology, our group has used a minimally-invasive fine-needle aspiration technique to measure intratesticular hormones in normal healthy men. Herein, we present a post-hoc analysis of the safety and efficacy of testicular fine-needle aspiration (FNA) completed as part of six clinical trials. From 2001 through 2011, a total of 404 procedures were conducted among 163 research volunteers, 85.9% of which were successful in obtaining sufficient fluid for the measurement of intratesticular steroid concentrations. Pain was the most common side effect, with 36.8% of procedures associated with moderate procedural pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and abated within a few days. Mild local bruising occurred with 14.9% of procedures. Two serious adverse events (0.5%) required surgical intervention. The risk of an adverse event was not associated with age, body mass index, testicular size, or the volume of fluid aspirated. Testicular FNA to obtain fluid for measurement of intratesticular steroid concentrations frequently causes mild to moderate procedural pain, but serious adverse events occur rarely. Testicular FNA has been instrumental for defining human intratesticular hormone physiology and is a minimally-invasive, safe, effective method for obtaining fluid for research on testicular physiology and pathology.