A Novel Risk Score to Predict Hungry Bone Syndrome After Parathyroidectomy for Renal Hyperparathyroidism.

OBJECTIVE: Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS: A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS: Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION: Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.

American Association of Clinical Endocrinology Disease State Clinical Review: The Clinical Utility of Minimally Invasive Interventional Procedures in the Management of Benign and Malignant Thyroid Lesions.

OBJECTIVE: The objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes. METHODS: A literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review. RESULTS: Minimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer. CONCLUSION: Surgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.

Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

OBJECTIVE: The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States. METHODS: The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSION: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

OBJECTIVE: To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy. BACKGROUND: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the US. METHODS: The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation. CONCLUSIONS: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.

Thyroid cancer is more likely to be detected incidentally on imaging in private hospital patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing. Patients with higher socioeconomic status have higher rates of WDTC, possibly due to increased imaging and overdiagnosis. We compared methods of WDTC diagnosis in patients treated at a public and an adjacent private university hospital. MATERIALS AND METHODS: Patients with WDTC at the two hospitals between 2004 and 2010 were included. Patients were categorized into having their WDTC discovered on physical examination or on unrelated imaging. Demographic and pathologic data were collected. T-test was used for quantitative variables, and chi-squared test was used for categorical values. Binomial logistic regression was used to asses for confounding. RESULTS: Among 473 patients, 402 (85%) were from the university hospital, and 71 (15%) were from the public hospital. Patients from the university hospital were older (mean age: 49 versus 44, P = 0.02) and had a different racial composition compared to those from the public hospital. The patients at the public hospital had larger tumors (23 versus 18 mm, P = 0.04). Patients from the university hospital were more likely to have WDTC detected by imaging than patients in the public hospital (46% versus 28%, P < 0.01) on univariate analysis. CONCLUSIONS: This study demonstrates that patients with WDTC treated at a university hospital are more likely to have their tumor detected on unrelated imaging than those treated at a public hospital. These data may support the hypothesis that patients with improved insurance are more likely to have WDTC detected by imaging.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

OBJECTIVE: Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. METHODS: This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. RESULTS: From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. CONCLUSION: The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. ABBREVIATIONS: AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

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

Background and Objective: 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: 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: 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: 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.

Management of Poorly Differentiated Thyroid Cancer and Differentiated High-Grade Thyroid Carcinoma.

Thyroid carcinoma of follicular cell origin exists on a histopathologic and clinical spectrum. The authors focus on the category of tumors that fall between the very favorable well-differentiated thyroid carcinomas and the very unfavorable anaplastic thyroid carcinomas. These intermediately aggressive tumors include poorly differentiated thyroid carcinoma and the newly defined differentiated high-grade thyroid carcinoma. Both diagnoses require certain histopathologic requirements be met in order to accurately identify these tumors post-operatively. Management remains primarily surgical though adjunctive treatments such as molecular targeted therapies (eg, tyrosine kinase inhibitors) and differentiation therapy (to restore tumor response to radioactive iodine) are also becoming available.

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

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.

Repeat Fine-Needle Aspiration With Molecular Analysis in Management of Indeterminate Thyroid Nodules.

OBJECTIVE: To analyze clinical outcomes in a series of indeterminate thyroid nodules (ITNs) with repeat fine-needle aspiration (FNA) biopsy and results of genomic classifier. STUDY DESIGN: Historical chart review. SETTING: Tertiary care center. METHODS: We reviewed FNA samples from subjects with Bethesda III or IV diagnoses from January 2015 to December 2018 at a single institution and selected those with repeat FNA and ThyroSeq testing of the same nodule. Patient demographics, Bethesda classifications, ThyroSeq results, treatment detail, and surgical pathology, when available, were analyzed. RESULTS: Ninety-six patients with cytologic diagnosis of ITN, repeat FNA, and ThyroSeq testing were identified. Following repeat FNA, 55 nodules (57%) remained ITN; 40 (42%) were reclassified as benign; and 1 (1%) was reclassified as suspicious for malignancy. In 31 patients with ThyroSeq analysis accompanying initial and repeat FNA, 26 (84%) had the same result on each, while 5 (16%) tested ThyroSeq positive following an initially negative result (κ = 0.24). Most nodules that were downgraded to Bethesda II on repeat FNA (37/40, 93%) were managed nonsurgically. Patients with ThyroSeq-positive results were treated with surgery more often (25/28, 89%) than patients with ThyroSeq-negative results (11/68, 16%; P < .0001). In excised nodules, the prevalence of malignancy and noninvasive follicular thyroid neoplasm with papillary-like nuclear features was 28% (n = 10) and 22% (n = 8), respectively, and all malignancies were low risk. CONCLUSION: In this case series, repeat FNA helped patients with ITNs avoid diagnostic surgery through reclassification to benign cytology. The risk of high-risk malignancy in ThyroSeq-positive nodules with repeat indeterminate cytology was low.

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?

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: 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.

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

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: 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.

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

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: 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.

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

Background: The primary goal of this interdisciplinary consensus statement is to provide a framework for the safe adoption and implementation of ablation technologies for benign thyroid nodules. Summary: This consensus statement is organized around three key themes: (1) safety of ablation techniques and their implementation, (2) optimal skillset criteria for proceduralists performing ablative procedures, and (3) defining expectations of success for this treatment option given its unique risks and benefits. Ablation safety considerations in pre-procedural, peri-procedural, and post-procedural settings are discussed, including clinical factors related to patient selection and counseling, anesthetic and technical considerations to optimize patient safety, peri-procedural risk mitigation strategies, post-procedural complication management, and safe follow-up practices. Prior training, knowledge, and steps that should be considered by any physician who desires to incorporate thyroid nodule ablation into their practice are defined and discussed. Examples of successful clinical practice implementation models of this emerging technology are provided. Conclusions: Thyroid ablative procedures provide valid alternative treatment strategies to conventional surgical management for a subset of patients with symptomatic benign thyroid nodules. Careful patient and nodule selection are critical to the success of these procedures as is extensive pre-procedural patient counseling. Although these emerging technologies hold great promise, they are not without risk and require the development of a unique skillset and environment for optimal, safe performance and consistent outcomes.