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Current guidelines for the application of radiofrequency ablation for thyroid nodules: a narrative review

Lui, Michael S; Patel, Kepal N
BACKGROUND AND OBJECTIVE/UNASSIGNED:Thyroid nodules are frequently incidentally found on physical exam or imaging for an unrelated work-up. Although surgery remains the gold standard for treating symptomatic benign and/or malignant thyroid nodules, radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option for high risk patients and those who decline surgery. The novel application of RFA to treat thyroid disease was originally described for symptomatic, benign thyroid nodules. Since then, several studies have tried to expand its indication to treat primary and recurrent well-differentiated thyroid cancer. The high success rates and the low complication profile, has allowed for quick adoption of RFA as a treatment option for well-selected patients with benign thyroid nodules and locoregional recurrent thyroid malignancy. As such, multidisciplinary guidelines and consensus statements were developed to standardize indications, techniques, outcome measures, and follow-up to ensure the best patient care. This article summarizes the current indications and recommendations to help guide clinicians on how best to effectively and safely utilize RFA to treat thyroid disease. METHODS/UNASSIGNED:A PubMed/MEDLINE search between 2000-2022 using a combination of "radiofrequency ablation", "RFA", "thyroid nodule", and "guidelines" was conducted. The inclusion criteria were articles published in English which offered recommendations on RFA use for thyroid nodules. KEY CONTENT AND FINDINGS/UNASSIGNED:For symptomatic, benign thyroid nodules, RFA is effective at significantly reducing nodule volume. For large nodules, multiple RFA sessions may be needed to achieve clinically significant volume reduction. Patients undergoing RFA for autonomously functioning thyroid nodules may see symptomatic relief but success rates are variable. RFA may serve a curative or palliative role in recurrent well-differentiated thyroid cancers. There is little data describing the use of RFA for primary well-differentiated thyroid cancer >1 cm and the role of RFA for thyroid microcarcinomas remains controversial. CONCLUSIONS/UNASSIGNED:RFA is a safe minimally invasive technique and may be considered, in appropriate circumstances, a first-line treatment option for benign thyroid nodules. Practices adopting RFA will likely increase as more clinicians become familiar with this technique, highlighting the importance of developing standardized guidelines.
PMCID:10839702
PMID: 38323237
ISSN: 2227-684x
CID: 5632662

Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

Wright, Kyla; Fisher, Jason C.; Rothberger, Gary D.; Prescott, Jason D.; Allendorf, John D.; Patel, Kepal; Suh, Insoo
Background: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer"”Gallium-68 DOTATATE"”has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. Methods: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. Results: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. Conclusion: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.
SCOPUS:85175319745
ISSN: 0039-6060
CID: 5616582

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

Chiosea, Simion; Hodak, Steven P; Yip, Linwah; Abraham, Devaprabu; Baldwin, Chelsey; Baloch, Zubair; Gulec, Seza A; Hannoush, Zeina C; Haugen, Bryan R; Joseph, Lija; Kargi, Atil Y; Khanafshar, Elham; Livhits, Masha J; McIver, Bryan; Patel, Kepal; Patel, Snehal G; Randolph, Gregory W; Shaha, Ashok R; Sharma, Jyotirmay; Stathatos, Nikolaos; van Zante, Annemieke; Carty, Sally E; Nikiforov, Yuri E; Nikiforova, Marina N
CONTEXT/BACKGROUND: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/METHODS:Retrospective analysis of FNA samples tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier. SETTING/METHODS:UPMC MGP laboratory. PARTICIPANTS/METHODS:A total of 50,734 BCIII-VI nodules from 48,225 patients. INTERVENTION/METHODS:None. MAIN OUTCOME MEASURES/METHODS: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.
PMID: 37071871
ISSN: 1945-7197
CID: 5466102

General Principles for the Safe Performance, Training, and Adoption of Ablation Techniques for Benign Thyroid Nodules: An American Thyroid Association Statement

Sinclair, Catherine F; Baek, Jung Hwan; Hands, Kathleen E; Hodak, Steven P; Huber, Timothy C; Hussain, Iram; Lang, Brian Hung-Hin; Noel, Julia E; Papaleontiou, Maria; Patel, Kepal N; Russ, Gilles; Russell, Jonathon; Spiezia, Stefano; Kuo, Jennifer H
PMCID:10611977
PMID: 37642289
ISSN: 1557-9077
CID: 5609202

Invited Commentary: The Path Toward Broader Validation and Adoption of Transoral Thyroidectomy

Suh, Insoo; Patel, Kepal N
PMID: 36853348
ISSN: 1432-2323
CID: 5466962

Case Report: Giant Thyroid Angiolipoma-Challenging Clinical Diagnosis and Novel Genetic Alterations

Wilkins, Reid; Zan, Elcin; Leonardi, Olga; Patel, Kepal N; Jacobson, Adam S; Jour, George; Liu, Cheng Z; Zhou, Fang
BACKGROUND:A 64-year-old man presented with a 7.8 cm lipomatous thyroid mass discovered on magnetic resonance imaging. METHODS:After two non-diagnostic fine needle aspirations (FNAs) were performed, computed tomography (CT) revealed features concerning for malignancy including central necrosis and infiltrative borders. A third FNA was still non-diagnostic. Total thyroidectomy was performed. RESULTS:Upon pathologic examination, the final diagnosis was primary thyroid angiolipoma. The lesion contained central fat necrosis with ischemic features, attributable to the FNAs. CONCLUSION/CONCLUSIONS:Ours is the third published case report of this rare entity. To date, no lipomatous thyroid tumor has undergone extensive genomic testing. Next-generation sequencing of our case revealed multiple genetic alterations, supporting the concept of angiolipomas being true neoplasms. Whereas the two previously reported cases in the literature were radiographically much smaller and appeared indolent, the large tumor in our case exhibited radiographic features concerning for liposarcoma, which belied the benign final pathologic diagnosis. Our case demonstrates that conservative surgical management (partial thyroidectomy) may be considered for lipomatous thyroid tumors, with further interventions to be determined only after final pathologic diagnosis.
PMID: 36255668
ISSN: 1936-0568
CID: 5360392

Implementation of a formal sleep center-based screening protocol for primary aldosteronism in patients with obstructive sleep apnea

Wright, Kyla; Mahmoudi, Mandana; Agrawal, Nidhi; Simpson, Hope; Lui, Michael S; Pachter, H Leon; Patel, Kepal; Prescott, Jason; Suh, Insoo
BACKGROUND:There is a bidirectional association between primary aldosteronism and obstructive sleep apnea, with evidence suggesting that the treatment of primary aldosteronism can reduce obstructive sleep apnea severity. Current guidelines recommend screening for primary aldosteronism in patients with comorbid hypertension and obstructive sleep apnea, identifying potential candidates for treatment. However, emerging data suggest current screening practices are unsatisfactory. Moreover, data regarding the true incidence of primary aldosteronism among this population are limited. This study aimed to assess the primary aldosteronism screening rate among patients with obstructive sleep apnea and hypertension at our institution and estimate the prevalence of primary aldosteronism among this population. METHODS:Sleep studies conducted at our institution between January and September 2021 were retrospectively reviewed. Adult patients with a sleep study diagnostic of obstructive sleep apnea (respiratory disturbance index ≥5) and a diagnosis of hypertension were included. Patient medical records were reviewed and laboratory data of those with biochemical screening for primary aldosteronism were assessed by an experienced endocrinologist. Screening rates were compared before and after initiation of a screening protocol in accordance with the 2016 Endocrine Society guidelines. RESULTS:A total of 1,005 patients undergoing sleep studies were reviewed; 354 patients had comorbid obstructive sleep apnea and hypertension. Patients were predominantly male (67%), with a mean age of 58 years (standard deviation = 12.9) and mean body mass index of 34 (standard deviation = 8.1). The screening rate for primary aldosteronism among included patients was 19% (n = 67). The screening rate was significantly higher after initiation of a dedicated primary aldosteronism screening protocol (23% vs 12% prior; P = .01). Fourteen screens (21%) were positive for primary aldosteronism, whereas 45 (67%) were negative and 8 (12%) were indeterminate. Four had prior abdominal cross-sectional imaging, with 3 revealing an adrenal adenoma. Compared with patients without primary aldosteronism, patients with positive primary aldosteronism screens were more likely to have a history of hypokalemia (36% vs 4.4%; P = .002). The frequency of hyperlipidemia, diabetes mellitus, and left ventricular hypertrophy did not differ between patients with positive versus negative screens. CONCLUSION/CONCLUSIONS:Current screening practices for primary aldosteronism among patients with comorbid obstructive sleep apnea and hypertension are suboptimal. Patients evaluated at sleep centers may represent an optimal population for screening, as the prevalence of primary aldosteronism among this cohort appears high.
PMID: 36198493
ISSN: 1532-7361
CID: 5361722

Recorder's Note [Editorial]

Patel, Kepal N
PMID: 36402609
ISSN: 1532-7361
CID: 5373772

The clinical significance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category 5 thyroid nodules: Not as risky as we think?

Wright, Kyla; Brandler, Tamar C; Fisher, Jason C; Rothberger, Gary D; Givi, Babak; Prescott, Jason; Suh, Insoo; Patel, Kepal N
BACKGROUND:Although the prevalence of thyroid nodules is high, few prove to be malignant. Based on sonographic features, the American College of Radiology Thyroid Imaging Reporting and Data System categorizes malignancy risk of thyroid nodules with associated management recommendations for each category level. Malignancy rates among nodules with a highly suspicious Thyroid Imaging Reporting and Data System category 5 warrant examination in the context of additional risk stratification tools, including cytopathology and molecular testing. METHODS:All patients who underwent fine-needle aspiration biopsy for Thyroid Imaging Reporting and Data System category 5 nodules from January 2018 to September 2021 in a large integrated academic health system were reviewed. Using the Bethesda System for Reporting Thyroid Cytopathology, categories V and VI were set as malignant. Molecular testing (ThyroSeq version 3; Rye Brook, NY) yielding ≥50% risk of malignancy was deemed positive and correlated with surgical pathology. RESULTS:A total of 496 Thyroid Imaging Reporting and Data System category 5 nodules were identified. On fine-needle aspiration cytopathology, 61 (12.3%) were malignant. The breakdown included Bethesda System for Reporting Thyroid Cytopathology I, 15 (3%); II, 362 (73%); III, 52 (10.5%); IV, 5 (1%); V, 6 (1.3%); and VI, 55 (11.1%). Of Bethesda System for Reporting Thyroid Cytopathology III/IV nodules with molecular testing (n = 53), 24.5% yielded positive results. In total, 42 (8.5%) nodules underwent surgical resection, most of which were Bethesda System for Reporting Thyroid Cytopathology VI (n = 26, 61.9%). Of excised nodules, 33 (78.6%) nodules were malignant, 6 (14.3%) benign, and 3 (7.1%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features. All Thyroid Imaging Reporting and Data System category 5 nodules with malignant cytology (Bethesda System for Reporting Thyroid Cytopathology V/VI) that underwent surgery were malignant on histopathology. On average, the total Thyroid Imaging Reporting and Data System points were higher in malignant nodules compared with benign (9.3 vs 7.3; P = .015). Moreover, benign nodules more frequently received Thyroid Imaging Reporting and Data System points when the radiologist was unable to determine composition or echogenicity (33% vs 3% among malignant nodules; P = .01). CONCLUSION/CONCLUSIONS:Thyroid Imaging Reporting and Data System category 5 designation in thyroid nodules is associated with a lower risk of malignancy than previously reported. Benign and malignant nodules with Thyroid Imaging Reporting and Data System category 5 designation have discrepancies in certain Thyroid Imaging Reporting and Data System characteristics and individual points assigned, which may offer an opportunity for quality improvement and standardization measures in ultrasound reporting practices.
PMID: 36511283
ISSN: 1532-7361
CID: 5379322

The Year in Thyroidology: Surgical Science

Patel, Kepal N
PMID: 36511381
ISSN: 1557-9077
CID: 5409212