Faculty Bibliography

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.

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.

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.

BACKGROUND:Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS:A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS:Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION/CONCLUSIONS:Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

BACKGROUND:The association between exposure to air pollution and papillary thyroid carcinoma is unknown. We sought to estimate the relationship between long-term exposure to the fine (diameter ≤ 2.5 μm) particulate matter component of air pollution and the risk of papillary thyroid cancer. METHODS:Adult (age ≥18) patients with newly diagnosed papillary thyroid carcinoma between January 1, 2013 and December 31, 2016 across a single health system were identified using electronic medical records. Data from 1,990 patients with papillary thyroid carcinoma were compared with 3,980 age- and sex-matched control subjects without any evidence of thyroid disease. Cumulative fine (diameter <2.5 μm) particulate matter exposure was estimated by incorporating patients' residential zip codes into a deep learning neural networks model, which uses both meteorological and satellite-based measurements. Conditional logistic regression was performed to assess for association between papillary thyroid carcinoma and increasing fine (diameter ≤2.5 μm) particulate matter concentrations over 1, 2, and 3 years of cumulative exposure preceding papillary thyroid carcinoma diagnosis. RESULTS:n = 0.04). Among current smokers (n = 623), the risk of developing papillary thyroid carcinoma was highest (adjusted odds ratio = 1.35, 95% confidence interval: 1.12-1.63). CONCLUSION/CONCLUSIONS:Increasing concentration of fine (diameter ≤2.5 μm) particulate matter in air pollution is significantly associated with the incidence of papillary thyroid carcinoma with 2 and 3 years of exposure. Our novel findings provide additional insight into the potential associations between risk factors and papillary thyroid carcinoma and warrant further investigation, specifically in areas with high levels of air pollution both nationally and internationally.

BACKGROUND:Secondary hyperparathyroidism (SHPT) affects nearly all patients on maintenance dialysis therapy. SHPT treatment options have considerably evolved over the past 2 decades, but vary in degree of improvement in SHPT. Therefore, we hypothesize that the risks of adverse outcomes after kidney transplantation (KT) may differ by SHPT treatment. METHODS:Using the SRTR and Medicare claims data, we identified 5,094 adults (age≥18) treated with cinacalcet or parathyroidectomy for SHPT prior to receiving KT between 2007-2016. We quantified the association between SHPT treatment and delayed graft function and acute rejection using adjusted logistic models and tertiary hyperparathyroidism (THPT), graft failure, and death using adjusted Cox proportional hazards; we tested whether these associations differed by patient characteristics. RESULTS:Of 5094 KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure or death. However, compared to patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (aHR=0.56, 95%CI: 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (pinteraction=0.039). Among patients on maintenance dialysis therapy for ≥3 years prior to KT (n=3,477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (aHR=0.43, 95%CI: 0.24-0.79). CONCLUSIONS:Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 years. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.

BACKGROUND:Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS:A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS:Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION/CONCLUSIONS:In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

BACKGROUND:Current data regarding the risk of malignancy in a large thyroid nodule with benign fine-needle aspiration biopsy(FNAB) is conflicting. We investigated the impact of patient age on the risk of malignancy in nodules≥4 cm with benign cytology. METHODS:We performed a single-institution retrospective review of patients who underwent surgery from 07/2008-08/2019 for a cytologically benign thyroid nodule ≥4 cm. The relationship between malignant histopathology and patient and ultrasound features was assessed with multivariable logistic regression. RESULTS:Of 474 nodules identified, 25(5.3%) were malignant on final pathology. In patients <55 years old, 21/273(7.7%) nodules were malignant, compared to 4/201(2.0%) in patients ≥55. Patient age ≥55 was independently associated with significantly lower risk of malignancy(OR:0.2,95%CI:0.1-0.7,p = 0.011). Increasing nodule size >4 cm and high-risk ultrasound features were not associated with risk of malignancy(OR:1.0,95%CI:0.7-1.4,p = 0.980, and OR:9.6,95%CI:0.9-107.8,p = 0.066, respectively). CONCLUSIONS:Patients <55 years old are 3.7-fold more likely to have a falsely benign FNA biopsy in a nodule≥4 cm.

BACKGROUND:Prior studies demonstrated that older adults tend to undergo less surgery for thyroid cancer. Our objective was to use a discrete choice experiment to identify factors influencing surgical decision-making for older adults with thyroid cancer. METHODS:Active and candidate members of the American Association of Endocrine Surgeons were invited to participate in a web-based survey. Multinomial logistic regression was utilized to assess patient and surgeon factors associated with treatment choices. RESULTS:Complete survey response rate was 25.7%. Most respondents were high-volume surgeons (88.5%) at academic centers (76.9%). Multinomial logistic regression demonstrated that patient age was the strongest predictor of management. Increasing age and comorbidities were associated with the choice for active surveillance (P = .000), not performing a lymphadenectomy in patients with nodal metastases (relative-risk ratio: 2.5, 95% CI: 1.4-4.2, P = .002 and relative-risk ratio: 1.6, 95% CI: 1.2-2.1, P = .004, respectively), and recommending hemithyroidectomy versus total thyroidectomy for a cancer >4 cm (relative-risk ratio: 4.4, 95% CI: 2.5-7.9, P = .000 and relative-risk ratio: 3.4, 95% CI: 2.3-5.1, P = .000, respectively). Surgeons with ≥10 years of experience (relative-risk ratio: 3.3, 95% CI: 1.1-10.3, P = .039) favored total thyroidectomy for a cancer <4 cm, and nonfellowship trained surgeons (relative-risk ratio: 7.3, 95% CI: 1.3-42.2, P = .027) opted for thyroidectomy without lymphadenectomy for lateral neck nodal metastases. CONCLUSION:This study highlights the variation in surgical management of older adults with thyroid cancer and demonstrates the influence of patient age, comorbidities, surgeon experience, and fellowship training on management of this population.

OBJECTIVE:Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation. METHODS:Thyroid surgery cases at a single institution from 2005-2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings. RESULTS:Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology. CONCLUSION/CONCLUSIONS:Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy. ABBREVIATIONS/BACKGROUND:ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound.