Background: Differentiated thyroid cancer (DTC) is the most prevalent cancer of thyroid and is among the most frequently diagnosed cancers in the United States. The practice guidelines of the American Thyroid Association (ATA) for DTC management in adult patients (previously combined with thyroid nodules) were published initially in 1996, with subsequent revisions based on advances in the field. The goal of this update is to provide clinicians, patients, researchers, and those involved in health policy with rigorous, comprehensive, and contemporary guidelines to assist in the management of adult patients with DTC, emphasizing the patient journey beginning with a thyroid cancer diagnosis. Methods: The questions addressed were based, in part, on prior versions of the guidelines, with input from a larger, more diverse complement of stakeholders. The panel included members from multiple specialties involved in thyroid cancer care, including a patient advocate and an expert in systematic reviews/meta-analyses/guidelines who educated and supported task force members. The panel conducted systematic literature reviews to inform the recommendations and commissioned two additional systematic reviews. Published English-language articles were eligible for inclusion, with a final search date of July 1, 2024. A modified Grading of Recommendations Assessment, Development and Evaluation system was used for critical appraisal of evidence and determining the quality of data. The guidelines panel had editorial independence from the ATA. Competing interests of task force members were pre-vetted, regularly updated, communicated with task force members, and assessed and managed by ATA leadership and the Clinical Practice Guidelines and Statements Committee. Results: These revised guidelines begin with the initial cancer diagnosis and continue with recommendations for staging and risk assessment, initial treatment decisions, assessment of treatment responses, monitoring approaches, diagnostic testing, and subsequent therapies based on the strength of evidence for response and consideration of side effects and outcomes. Patient-reported outcomes and identified areas of need for additional high-quality research are highlighted. Conclusions: These revised evidence-based recommendations inform clinical decision-making in the management of DTC that reflect the changing science and optimize the evidence-based clinical care of patients throughout their journey with DTC. Critical areas of need for additional research are highlighted. 

2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer.

CONTEXT
Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine-needle aspiration (FNA) samples has not been reported.


OBJECTIVE
To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules.


DESIGN
Retrospective analysis of FNA samples tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier.


SETTING
UPMC MGP laboratory.


PARTICIPANTS
A total of 50,734 BCIII-VI nodules from 48,225 patients.


INTERVENTION
None.


MAIN OUTCOME MEASURES
Prevalence of diagnostic, prognostic, and targetable genetic alterations.


RESULTS
Among 50,734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alteration. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.2% of cases.


CONCLUSIONS
In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutationsand targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.

Molecular Profiling of 50,734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management.

Simple Summary According to the American Cancer Society, approximately 53,000 new cases of thyroid cancer were diagnosed and more than 2200 people died from the disease in 2020. New developments in molecular imaging are significantly improving thyroid cancer diagnostics and therapy. Continuous research in molecular imaging techniques additionally contributes to an understanding of a variety of diseases and enables more efficient care of thyroid cancer patients. Molecular imaging-based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theragnostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contributes to the success of personalized medicine. This review details the inception of molecular imaging and theragnostic applications for thyroid cancer management. Abstract Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., 131I, 123I, 124I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [18F]F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT and/or [18F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review.

/pdf/molecular-imaging-and-theragnostics-of-thyroid-cancers-2uort0sz.pdf

Molecular Imaging and Theragnostics of Thyroid Cancers

Simple Summary The aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, present several molecular tests, and discuss the clinical applications of identifying these markers supported by the clinical experience of several high-volume thyroid cancer specialists at the McGill university teaching hospitals in Montreal, Canada. Abstract In the past few decades, molecular characterization of thyroid cancer has made significant progress and is able to identify thyroid-cancer-related molecular markers that can then be applied clinically for improved decision making. The aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, present several molecular tests, and discuss the clinical applications of identifying these markers supported by the clinical experience of several high-volume thyroid cancer specialists at the McGill university hospitals in Montreal, Canada. Our group experience showed that molecular testing can reclassify more than half of the patients with indeterminate thyroid nodules (Bethesda III and IV) into benign and spare these patients from unnecessary diagnostic surgery. Furthermore, it can help optimize the initial management in thyroid cancers with no evidence of high risk of recurrence of disease preoperatively. While routine molecular testing is not firmly established for thyroid FNA specimens that are suspicious or positive for malignancy (Bethesda V and VI), knowledge of a thyroid nodule’s molecular risk group profile in such cases, together with its clinical and radiologic features, can help select the optimal surgical options (lobectomy versus upfront total thyroidectomy and central neck dissection), as demonstrated by our studies.

/pdf/molecular-testing-for-thyroid-nodules-the-experience-at-1g6cnu8w.pdf

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada

Seeking Optimal Management for Radioactive Iodine Therapy-induced Adverse Effects.

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).

/pdf/thyroid-carcinoma-version-2-2022-nccn-clinical-practice-3hfa8dr3.pdf

Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Guidelines® Insights: Thyroid Carcinoma, Version 1.2025.

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Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Guidelines® Insights: Thyroid Carcinoma, Version 1.2025.