Background: The American Association of Endocrine Surgeons suggests screening for familial hypocalciuric hypercalcemia for 24-hour urine calcium <100 mg and for calcium to creatinine clearance ratio <1%. We explored the biochemical and clinical profiles of genetically tested patients to determine the usefulness of these recommendations. Methods: This was a retrospective review of patients who underwent analysis of the calcium-sensing receptor gene. Results: In total, 401 patients were identified between 2005 and 2024; 332 (83%) were negative for a mutation, 44 (11%) were positive, and 25 (6%) had variants of unknown significance. Median serum calcium was lower in patients who were negative (negative 10.1 mg/dL, variants of unknown significance 10.6 mg/dL, positive 10.9 mg/dL). Median urine calcium was lower in patients who were positive (negative 110 mg, variants of unknown significance 149 mg, positive 82 mg). Median parathyroid hormone levels were comparable between groups (negative 65 pg/mL, variants of unknown significance 58 pg/mL, positive 60 pg/mL). Eight of 21 (38%) patients who tested positive had urine calcium >100 mg and 5 of 21 (24%) had urine calcium >200 mg. Eight of 35 (23%) patients who were positive had a calcium to creatinine clearance ratio >1%. Urine calcium and calcium to creatinine clearance ratio receiver operating characteristic curves showed poor performance in identifying patients with familial hypocalciuric hypercalcemia (area under the curve [95% confidence interval]): 0.55 [0.45-0.65] and 0.63 [0.57-0.7], respectively. For positive patients with imaging, sestamibi was inconclusive or nonlocalizing for 13 of 23 and showed multiglandular disease for localizing scans in 7 of 10. Ultrasound was nonlocalizing or equivocal for 11 of 13. In total, 212 of 401 patients (53%) underwent surgery; 100 of 212 were tested preoperatively (0/100 positive, 5/100 variants of unknown significance) and 112 of 212 patients were tested postoperatively (15/112 positive, 10/112 variants of unknown significance). Conclusion: Familial hypocalciuric hypercalcemia demonstrates non-negligible biochemical overlap with primary hyperparathyroidism, with many patients having a urine calcium value greater than the American Association of Endocrine Surgeons suggested threshold for considering genetic evaluation. More frequent genetic testing beyond urine measurements may help identify more patients with familial hypocalciuric hypercalcemia. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Background: Oncocytic adrenal neoplasms, defined by ≥90 % of oncocytic cells, are rare. The significance of oncocytic changes within an adrenal neoplasm remains unclear. Methods: A retrospective study of adults who underwent adrenalectomy at a large center identified pure oncocytic neoplasms on final pathology (1997-2022). Neoplasms were categorized based on Lin-Weiss-Bisceglia system as malignant, benign, or of uncertain malignant potential. Analysis was performed using Fisher exact, Kruskal-Wallis tests, and Kaplan-Meier analysis. Results: Among a total of 33 patients, 24% had benign, 36% malignant, and 39% neoplasm of uncertain malignant potential. None of the benign neoplasms recurred, while 50% of the malignant neoplasms recurred (median of 40 months). Two of 13 neoplasms initially thought to be of uncertain malignant potential recurred as distant metastatic adrenocortical carcinoma at 11 and 25 months, over a median follow-up duration of 31 months. Ki67% was available for 20 patients: median (IQR) Ki67% was 5 (1, 5) for benign, 10 (6, 15) for malignant, and 6.5 (5, 10) for neoplasms of uncertain behavior, P = 0.05. Recurred neoplasms had higher Ki67% at initial resection compared to cases that did not recur. Conclusion: While oncocytic adrenal neoplasms are rare, a significant proportion are malignant or have malignant potential. Judicious follow-up is required for oncocytic adrenal neoplasms of uncertain malignant potential, as they can recur as metastatic adrenocortical carcinoma. Ki67% should always be obtained in cases of malignancy or uncertain malignant potential as it can predict recurrence. Larger studies are needed to evaluate the appropriate follow-up protocols for these neoplasms.

Context: Data on giant pheochromocytomas (PHEO), defined based on size >= 10 cm, are scarce. Objective: to compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs. Design: retrospective cohort study, 2000-2023. Setting: referral center. Patients: consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at a 1:6 ratio. Outcomes: perioperative complications, metastases, mortality. Results: Of 828 patients with PHEO, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe catecholamine excess (76% vs 30%, P<.0001).Adrenalectomy was performed in 94% of patients with giant PHEOs and 100% referents. In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a higher perioperative complication rate (31% vs 10%, P=.004).During a median follow-up of 3 years, metastases developed at a higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease-specific mortality was 7% in patients with giant PHEOs and 0% in referents (P=.02). Conclusion: Patients with giant PHEO as compared to referents were more symptomatic, had a higher degree of catecholamine excess, and had a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up.

Background: H & uuml;rthle cell carcinoma (HCC) has traditionally been managed with total thyroidectomy. However, current evidence suggests a limited benefit to this approach due to the lack of radioactive iodine uptake. We sought to compare outcomes of HCC managed with hemi- (HEMI) vs. total thyroidectomy (TOTAL). Methods: A retrospective review of 309 patients who had surgery for HCC from 2000-2019 was performed. A subcohort was selected that matched each HEMI to a paired TOTAL on age and TNM stage. Associations of clinical and pathological features with surgery type were examined using paired t-tests and exact McNemar tests. Survival and recurrence were examined using Cox regression analysis. Results: 295 patients were in the study cohort, 42 (14%) HEMI and 253 (86%) TOTAL. Of the 42 HEMI; 69% were female, median age 57 years, Tx/T1 = 16, T2/T3 = 26, nodal disease in 1 and metastatic in 1. Compared to the 42 matched TOTAL, we found no associations of surgery type with age and TNM stage. Surgery type was also not associated with gender, race, pathology or focality (p > 0.05). Over a mean follow-up of 7.0 years in the matched cohort, there were 10 recurrences (8 TOTAL, 2 HEMI), 11 deaths (5 TOTAL, 6 HEMI) and 3 deaths from HCC (3 TOTAL, 0 HEMI). There were no differences in recurrence-free survival (p = 0.065), overall survival (p = 0.806) or disease-specific survival. Conclusion: Hemithyroidectomy is a reasonable treatment option for HCC. Extent of thyroidectomy does not affect recurrence-free survival or overall survival in our matched cohort. Synopsis: Single institution study with 295 patients with H & uuml;rthle cell carcinoma. A case-matched cohort to control for age and stage was used to compare hemi- versus total thyroidectomy. The extent of thyroidectomy did not affect recurrence free survival or overall survival.

Abstract Disclosure: B. Bahrani Fard: None. N. Nikravangolsefid: None. J. Maroun: None. A. Cross: None. T. Foster: None. T. McKenzie: None. W. Young Jr: None. B.M. Dy: None. M. Lyden: None. I. Bancos: None. Background: Giant pheochromocytomas (PHEO), defined based on size > 10 cm, are rare. Data on clinical presentation, management, and prognosis of giant PHEOs are scarce. Objectives: to determine prevalence of giant PHEO and compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs. Methods: We conducted a single-center retrospective cohort study of consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at 6:1 ratio, evaluated between 2000-2023. All variables were extracted from the electronic medical record. Results: Of 828 patients with PHEO evaluated between 2000 and 2023, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO were similar in age (median age 53 vs 55 years, P=.55), more frequently discovered based on symptoms (52% vs 32%, P=.04), and less likely to be bilateral (3% vs 12%, P=.31). Genetic testing was performed in 103 (48%) of patients, without group differences, however, patients with giant PHEO were less likely to have an associated germline mutation detected (7% vs 47%, P=.004). Patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe metanephrine excess >10 times above upper normal range (76% vs 30%, P<.0001). Adrenalectomy was performed in 94% of patients with giant PHEOs and in 100% referents, with higher rates of open adrenalectomy in giant PHEO (86% vs 14%, P<.0001). In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a longer hospital length of stay (laparoscopic: median 5 vs 2 days, P<.0001; open: median 6 vs 5 days, P=.24), and a higher complication rate (31% vs 10%, P=.006).Median follow up was 3 years (IQR 1-8) years, similar in patients and referents. Metastases developed at a much higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease specific mortality was 7% in patients with giant PHEOs and 0% in referents. Conclusion: Patients with giant PHEO were more symptomatic, had a higher degree of catecholamine excess, and a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up. Presentation: 6/2/2024

Introduction: Ethanol ablation can be utilized to manage insulinoma. We aimed to analyze our outcomes of endoscopic ultrasound (EUS) and intraoperative ultrasound (IOUS) guided Ethanol ablation of insulinoma. Methods: A single institution retrospective review of adults undergoing Ethanol ablation of benign pancreatic insulinoma (2007-2022) was performed. Outcomes were categorized as resolution of hypoglycemia, improvement, or no change at last follow-up. Results: A total of 16 patients underwent Ethanol ablation of benign insulinoma (N = 8 EUS, N = 8 IOUS): median age was 68 y, 8 (50%) were females, and 2 (12.5%) were associated with multiple endocrine neoplasia type-1. Median insulinoma size was 12 (range 7, 25) mm. Ethanol ablation was preferred over resection to avoid pancreaticoduodenectomy when it was not possible to enucleate the tumor in 10 (62.5%) patients while the rest underwent ablation due to being poor surgical candidates or because of a history of previous pancreatic resection. The median follow-up (interquartile range) was 43 (19.5, 81.5) mo. Resolution of hypoglycemia occurred in 11 patients (5 EUS, 6 IOUS), while the rest (3 EUS, 2 IOUS) experienced improvement in the severity and frequency of hypoglycemia. A single patient underwent resection following a previous ablation for symptomatic hypoglycemia 5 y after EUS guided ablation. Conclusions: Ethanol ablation provides an alternative therapeutic option for patients with insulinoma. Both EUS and IOUS guided approaches are associated with a favorable resolution rate although EUS guided ablation may require multiple procedures to optimize outcomes. (c) 2023 Published by Elsevier Inc.

Background: Percutaneous ethanol ablation has emerged as a treatment for recurrent papillary thyroid carcinoma in the lateral neck after compartment-oriented therapeutic lymphadenectomy. However, the safety and utility of percutaneous ethanol ablation as a primary treatment modality for lateral neck metastases remains undefined. We aimed to investigate long-term outcomes of percutaneous ethanol ablation of lateral neck papillary thyroid carcinoma recurrence both with and without prior lymphadenectomy. Methods: We conducted a retrospective study of patients with lateral neck papillary thyroid carcinoma treated with percutaneous ethanol ablation from 2013 to 2018. Patient characteristics, disease volume, morbidity, and recurrence (development of new lymphadenopathy within a percutaneous ethanol ablation-treated nodal compartment) were assessed. Results: We identified 117 patients who underwent percutaneous ethanol ablation for papillary thyroid carcinoma lateral neck metastasesd67 (57%) had a prior lateral neck dissection. Median follow-up after percutaneous ethanol ablation was 5.5 years (interquartile range 3.1-7.5). On average, 1.4 lymph nodes (range: 1-6) were treated. Three patients (3%) developed transient nerve-related complications after percutaneous ethanol ablation. Of 15 patients who underwent lateral neck dissection after percutaneous ethanol ablation (including patients undergoing repeat lateral neck dissection), dissection was "difficult" in 8 (53%) (7 of whom had previously undergone lateral neck dissection), and 4 (27%) developed complications (transient nerve dysfunction = 3, lymphatic leak = 1). Thirty-three patients (28%) developed recurrent papillary thyroid carcinoma. No difference in recurrence was seen between patients who did or did not undergo pre-percutaneous ethanol ablation lateral neck dissection (no pre-percutaneous ethanol ablation lateral neck dissection: 24%, pre-percutaneous ethanol ablation lateral neck dissection, 31%; hazard ratio = 1.27, 95% confidence interval 0.62-2.58; P = .514). Conclusion: Percutaneous ethanol ablation may be a safe primary treatment modality for papillary thyroid carcinoma lateral neck nodal recurrence in selected patients with low-volume nodal disease. (c) 2023 Elsevier Inc. All rights reserved.

Background: Current evidence suggests that cortisol secreting adrenocortical carcinoma has worse prognosis compared to non-secreting adrenocortical carcinoma. However, the effect of other secretory subtypes is unknown.Methods: This multicenter study within the American-Australian-Asian Adrenal Alliance included adults with adrenocortical carcinoma (1997-2020). We compared overall survival and disease-free survival among cortisol secreting, mixed cortisol/androgen secreting, androgen secreting, and non-secreting adrenocortical carcinoma.Results: Of the 807 patients (mean age 50), 719 included in the secretory subtype analysis: 24.5% were cortisol secreting, 13% androgen secreting, 28% mixed cortisol/androgen, 32.5% non-secreting, and 2% were mineralocorticoid secreting. Median overall survival and disease-free survival for the entire cohort were 60 and 9 months, respectively.Median overall survival was 36 months for cortisol, 30 for mixed, 60 for androgen secreting, and 115 for non-secreting adrenocortical carcinoma, P < .01. Median disease-free survival was 7 months for cortisol, 8 for mixed, 10 for androgen, and 12 for non-secreting adrenocortical carcinoma, P 1/4 .06. On multivariable analysis of age, sex, Ki67%, secretory subtype, stage, resection, and adjuvant therapy, predictors of worse overall survival were older age, higher Ki67%, stage IV, mixed secreting, R1, and no adjuvant therapy, P < .05. On subgroup analysis of R0 resection, predictors of worse overall survival included older age and higher Ki67%. Ki67% >= 40, stage III and cortisol secretion were associated with worse disease-free survival.Conclusion: Mixed cortisol/androgen secreting adrenocortical carcinoma was associated with worse overall survival, while cortisol or androgen secreting alone were not. Notably, among patients after R0 resection, secretory subtype did not affect overall survival. Cortisol secreting adrenocortical carcinoma demonstrated worse disease-free survival. Ki67% remained a strong predictor of worse overall survival and disease-free survival independent of stage.(c) 2023 Elsevier Inc. All rights reserved.

Abstract Disclosure: O. Hamidi: Advisory Board Member; Self; Corcept, Neurocrine Biosciences, Amryt Pharma, Recordati Rare Diseases, Lantheus, Xeris. B.H. Salama: None. P. Dogra: None. A.P. Dackiw: None. F. Nwariaku: None. A. Islam: None. A. Mehta: None. S.C. Oltmann: None. S. Mirfakhraee: None. T. McKenzie: None. T.R. Foster: None. M. Lyden: None. B.M. Dy: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) are at risk for adrenal insufficiency (AI) after unilateral adrenalectomy. We aimed to determine the prevalence, predictors, and duration of AI after unilateral adrenalectomy for MACS, and to compare baseline and peak cortisol post cosyntropin stimulation test (CST) in diagnosing AI. Methods: We conducted a dual-center retrospective cohort study of patients with MACS who underwent unilateral adrenalectomy and were evaluated with postoperative cosyntropin stimulation test (CST). AI was diagnosed when postoperative morning cortisol was <10μg/dL and/or CST peak cortisol was <18μg/dL. Baseline and CST peak cortisol levels were considered concordant when both met corresponding cut-offs. Biochemical (BSS) and clinical (CSS) severity scores for hypercortisolism were calculated. Results: In 100 adults with MACS (77% women, median age 56 years, interquartile range [IQR] 48-63), median adenoma size was 2.8 cm (IQR, 2.2-3.7), and 25 (25%) had bilateral nodules. Median BSS was 3 (IQR, 2-5) and median CSS was 4 (IQR, 2-8). After adrenalectomy, AI was diagnosed in 56 (56%) patients. AI was associated with higher BSS, larger tumor size, but not age, sex, BMI, tumor laterality. Baseline and CST peak cortisol levels were concordant in 76% of cases. In 14% of cases morning cortisol was <10μg/dL but CST peak cortisol was ≥18μg/dL, and in 10% of cases morning cortisol was ≥10μg/dL, but CST peak cortisol was <18μg/dL. On a multivariable analysis that included age, sex, BMI, BSS, laterality, and tumor size, only higher BSS (odd ratio [OR] = 1.6 per 1 point) was associated with postoperative baseline cortisol <10μg/dL (P<0.05 for all). Independent predictors of CST peak cortisol <18μg/dL were BSS (OR 1.5 per 1 point) and unilateral adenoma (OR 3.7). During a median postoperative follow up of 13 months, 33 (59%) patients recovered from AI. Median time to recovery was 6.0 months, with AI recovery in 28% of patients by 2 months, 42% by 3 months, 53% by 6 months, and 64% by 12 months. Conclusions: Prevalence of postoperative AI in MACS was 56%. Only 76% of patients had concordant baseline and CST peak cortisol, with peak CST cortisol being more commonly abnormal in patients treated for unilateral MACS. Patients with larger adenomas and higher BSS were at higher risk for AI. Patients with MACS should be counseled about the risk and duration of AI after adrenalectomy. Presentation: 6/3/2024

Background: We aim to evaluate the incidence of venous thromboembolism (VTE) following adrenalectomy. Methods: A retrospective analysis of the Collaborative Endocrine Surgery Quality Improvement Program was performed to assess incidence for VTE, including pulmonary embolism or deep vein thrombosis, in adults undergoing adrenalectomy (2014-2022). Results: 2567 patients undergoing adrenalectomy were included. Surgical approach was 10% open and 90% minimally invasive. Pathology was 13% malignant and 87% benign; 19% had hypercortisolism. VTE developed in 0.27% at a median of 8 days from surgery. The incidence was higher in primary adrenal malignancy compared to benign or metastases to the adrenals, p < 0.01. VTE was associated with longer hospital stay, longer operative time, readmission, and mortality. VTE rates were similar for hypercortisolism vs no hypercortisolism and between patients with clinical vs subclinical hypercortisolism. Conclusion: Although VTE following adrenalectomy is rare, it is more common in cases of primary adrenal malignancy, those with longer operations, or those requiring prolonged hospitalization.

Introduction Patients with primary hyperparathyroidism (1HPT) undergoing reoperative or subtotal parathyroidectomy (PTX) may undergo autotransplantation (ATX) when the viability of remaining tissue is unknown. This study aims to identify whether intraoperative parathyroid hormone levels (IOPTH) can determine ATX candidacy. Methods Patients with 1HPT who underwent PTX with ATX at our institution were identified. IOPTH and PTH values within 24 h, 2-4 weeks, and >1 month postoperative were analyzed. Patients were classified as either a candidate for ATX (low PTH after 2-4 weeks) or not a candidate based on postoperative PTH (normal PTH after 2-4 weeks). Associations of ATX candidate status with demographic and clinical attributes were studied. Results 268 had a reoperative (49%) or subtotal PTX with ATX. 151 had data for PTH analysis, and 21 (14%) were identified as candidates for ATX. The mean % decline in IOPTH from baseline to 20 min post-excision was 51% in noncandidates vs 73% in candidates (P = .002). The mean change in IOPTH from baseline to final was 52% in noncandidates and 83% in candidates (P = .009). A decrease in IOPTH from baseline to 20 min post-excision of 23.4% or greater or a final PTH of 52 pg/mL or less would be an indication for ATX. Of the 21 who needed an ATX, it failed in 10. Conclusion Parathyroid ATX is frequently unnecessary, and the viability is less than expected. While candidates for ATX have a greater IOPTH % decline at all points during surgery and a lower final IOPTH, the clinical practicality of using IOPTH to determine ATX candidacy is limited.

Background: There is limited long-term follow-up of patients undergoing parathyroidectomy. Recurrence is described as 4% to 10%. This study evaluated persistence and recurrence of hypercalcemia in primary hyperparathyroidism after parathyroidectomy. Methods: Single-institution retrospective (1965–2010) population-based cohort from Olmsted County (MN) of patients undergoing surgery for primary hyperparathyroidism. Patients’ demographic data, preoperative and postoperative laboratory values, clinical characteristics, surgical treatment, and follow-up were noted. Results: A total of 345 patients were identified, 75.7% female, and median age 58.4 years [interquartile range (IQR): 17.6]. In all, 68% of patients were asymptomatic and the most common symptoms were musculoskeletal complaints (28.4%) and nephrolithiasis (25.6%). Preoperative median serum calcium was 11 mg/dL (IQR: 10.8–11.4 mg/dL), and median parathyroid hormone was 90 pg/mL (IQR: 61–169 pg/dL). Bilateral cervical exploration was performed in 38% and single gland resection in 79% of cases. Median postoperative serum calcium was 9.2 mg/dL (IQR: 5.5–11.3). Nine percent of patients presented persistence of hypercalcemia, and recurrence was found in 14% of patients. Highest postoperative median serum calcium was 10 mg/dL (IQR: 6–12.4), and median number of postoperative calcium measurements was 10 (IQR: 0–102). Postoperative hypercalcemia was identified in 37% of patient. Fifty-three percent were attributed to secondary causes, most commonly medications, 22%. Three percent of patients required treatment for postoperative hypercalcemia. Median time to recurrence and death were 12.2 and 16.7 years, respectively. Conclusion: Recurrent hypercalcemia after successful parathyroidectomy is higher than previously reported. Most cases are transient and often associated to other factors with only the minority requiring treatment. Long-term follow-up of serum calcium should be considered in patients after successful parathyroidectomy.

PURPOSE:The purpose of this study is to evaluate the association between hyperparathyroidism (PHPT), parathyroid hormone levels, and calcium levels in patients diagnosed with benign fibro-osseous lesions such as fibrous dysplasia (FD), ossifying fibroma (OF), central giant cell granulomas (GCG).METHODS:This is a retrospective, single-center study from a sample of patients who underwent surgical treatment of FD, OF, and GCG at Mayo Clinic between 1996 and 2021. Patient demographics, history of PHPT, histopathological diagnosis, and relevant laboratory values such as parathyroid hormone (PTH), serum calcium, vitamin D, and alkaline phosphatase were collected.RESULTS:Of the patients diagnosed with FD (n = 64), OF (n = 24), and GCG (n = 5), a diagnosis of PHPT was found in 2 patients (3.1%), 1 patient (4.2%), and 0 patients (0%), respectively. Elevated PTH levels (>65 pg/mL) were observed in 3 patients (4.7%) with FD, 1 patient (4.2%) with OF, and 1 patient (20%) with GCG. Mean (standard deviation) calcium levels were 9.3 (0.6) mg/dL in the FD group, 9.4 (0.5) mg/dL in the OF group, and 9.3 (0.6) mg/dL in the GCG group. Patients with fibro-osseous jaw tumors including FD, OF, and GCG may have increased risk of PHPT compared to the general population.CONCLUSION:Patients with benign jaw tumors including FD, OF, and GCG may have increased risk of PHPT compared to the general population. Surgeons treating these benign tumors need to be cognizant of these findings, obtain appropriate laboratory studies, and incorporate multidisciplinary care including endocrinologists, endocrine surgeons, and maxillofacial surgeons.

Introduction: Parathyroidectomy is underperformed despite clear benefits in primary hy-perparathyroidism (PHPT). We evaluated disparities in receipt of parathyroidectomy following PHPT diagnosis to explore barriers to care. Methods: Adults diagnosed with PHPT 2013-2018 at a health system were identified. Rec-ommended indications for parathyroidectomy include age <50 y, calcium >11 mg/dL, or the presence of nephrolithiasis, hypercalciuria, nephrocalcinosis, decreased glomerular filtration rate, osteopenia, osteoporosis, or pathological fracture 1 y prior to diagnosis. Kaplan-Meier analysis assessed rates of parathyroidectomy within 12 mo following diagnosis as well as median time to parathyroidectomy, and multivariable Cox propor-tional hazards analyses assessed factors associated with undergoing parathyroidectomy. Results: Of 2409 patients, 75% were females, 12% aged <50 y, and 92% non-Hispanic White, while 52% had Medicaid/Medicare, 36% were commercial/self-pay or unin-sured, and 12% unknown. Parathyroidectomy was performed within 1 y in 50% of pa-tients. Within the 68% that met recommendations, parathyroidectomy was performed within 1 yin 54%; median time from diagnosis to surgery was shorter for males, patients aged <50 y, commercial/self-pay/no insurance patients (versus Medicaid/Medicare), and those with fewer comorbidities, P < 0.05. Multivariable analysis demonstrated non -Hispanic White patients and those with commercial/self-pay/uninsured were more likely to undergo parathyroidectomy after adjusting for comorbidity, age, and facility site. Among those strongly indicated, patients not on Medicare/Medicaid and aged <50 y were more likely to undergo parathyroidectomy after adjusting for race, comorbidity, and facility site. Conclusions: Disparities in parathyroidectomy for PHPT were observed. Insurance type was associated with undergoing parathyroidectomy; patients on governmental insurance were less likely to undergo surgery and waited longer for surgery despite strong indications. Barriers to referral and access to surgery should be investigated and addressed to optimize all patients' access to care. 2023 Elsevier Inc. All rights reserved.

Background: Medullary thyroid cancer is a neuroendocrine malignancy that can occur sporadically or as the result of genomic rearranged during transfection mutations. Medullary thyroid cancer has a higher rate of metastasis than well-differentiated thyroid cancer. Lateral neck dissection is often performed, and its prophylactic use is controversial. Methods: Single-center, retrospective review (2000-2017) of patients undergoing primary surgical treatment for medullary thyroid cancer who had negative lateral neck imaging preoperatively. Demographics, genetic associations, clinical, and imaging findings were analyzed. Locoregional recurrence, overall recurrence, and overall survival were examined. Results: A total of 110 patients were identified, of which 18 underwent prophylactic lateral neck dissection and 92 did not. Age, sex distribution, preoperative calcitonin levels, and follow-up were similar among groups. Overall recurrence was 20% for no prophylactic lateral neck dissection and 39% for prophylactic lateral neck dissection (P = .46). Most recurrences were locoregional recurrence, 7.6% for no prophylactic lateral neck dissection versus 22% for prophylactic lateral neck dissection (P = .08), half of it being to the lateral neck in both groups. A total of 7 patients from the no prophylactic lateral neck dissection group required treatment for recurrences versus 4 patients in prophylactic lateral neck dissection group (P = .57). Overall survival at 5 years was similar, 43% the no prophylactic lateral neck dissection group and 31% for prophylactic lateral neck dissection group (P = .52). Conclusion: Lateral neck dissection has no effect in decreasing locoregional or overall recurrences in medullary thyroid cancer and has no effect in overall survival when performed prophylactically at index surgical intervention. (c) 2021 Elsevier Inc. All rights reserved.

Introduction: Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare malignant tumor of the thyroid gland. It is believed to arise from thymic tissue or branchial pouch remnants showing thymic or branchial pouch differentiation. Besides its reported slow growing rate, its diagnostic importance lies in its representative metastatic potential. Approximately 50 cases have been reported around the globe and only 4 reported in Latin America. Herein, we report the first case of SETTLE from Ecuador.1 Description of Case: A 24-year-old man with no significant medical history and no risk factors for thyroid cancer was admitted to the head and neck department complaining of a rapidly growing neck mass. Physical examination revealed a 4.2 × 5.4 cm hard, painless, and immobile mass in the anterior neck. Complementary ultrasonography (US) showed a 4.1 × 3.2 cm left lobe mass with solid and cystic components. Fine-needle aspiration biopsy of the nodule was compatible with undifferentiated carcinoma with spindle cells Bethesda VI. Differential diagnoses at this time were anaplastic thyroid cancer, malignant teratoma, and ectopic thymoma. Before operating on the patient, a whole-body CT was ordered. It confirmed a thyroid mass raising from the left lobe of 5.3 × 4.3 × 4.3 cm comprising the trachea with some cervical lymph nodes up to 0.97 cm nodes in levels 2B, 3, 4, and 7 bilaterally, and level 1 only in the left compartment. There was no evidence of distant metastasis. In light of rapidly progressive obstructive symptoms, the patient underwent R0 total thyroidectomy using intraoperative recurrent laryngeal nerve monitoring, with central (2/6 positive) and left lateral (14/14 negative) neck lymph node dissection. The dissection was extended to the thymus. The patient was uneventfully discharged on postoperative day 1. No radiotherapy was planned. To confirm the suspected SETTLE, histopathology and immunohistochemistry were performed (positive for cytokeratin, CD99, TTF-1, and smooth muscle actin; negative for cytokeratin 9, thyroglobulin, and PAX8). The analysis confirmed the diagnosis of SETTLE in the left lobe of this patient's thyroid. We followed the patient at 1, 3, and 6 postoperative months and subsequently every 6 months to make sure to find metastases or recurrence in a timely manner. Recently the patient was seen at his 6-month follow-up, and there were no signs or symptoms of recurrence or metastasis. Discussion: To the best of our knowledge, this is the first Ecuadorian and the fifth Latin American patient being diagnosed with SETTLE. Although some studies have reported late metastasis, with the cervical lymph nodes, lungs, and mediastinum being the most frequently involved sites,2 the clinical course of SETTLE is quite unpredictable. Therefore, a strict long-term follow-up (as in this case) must be pursued even in patients with an apparent cure, as there is not enough evidence about SETTLE and its natural history. Our patient had cervical lymph node metastases, however, a correlation between recurrence or mortality risk and tumor size or lymph node metastasis at diagnosis has not been established.3 Regular physical examination should be considered in all visits complemented with neck US, and neck and chest CT performed every 6 months in the first 2 years and then annually even in the absence of specific symptoms.3,4 Although SETTLE is a rare neoplasm of the thyroid, physicians should include this entity as a differential diagnosis of other head and neck neoplasms. Finally, surgical resection is the mainstay therapy for SETTLE including resection of the primary and oligometastatic disease and there is no role for adjuvant chemotherapy or radiotherapy.5 The authors declare that no competing financial interests exist or any conflicts of interest or obligations resulting from this article. The case was obtained from the Head and Neck Department, ITECC (Instituto de la Tiroides y Enfermedades de Cabeza y Cuello), Quito, Ecuador. The patients provided informed written consent to disseminate this article. Runtime of video: 7 mins 8 secs This article was presented at the 90th Annual Meeting of the American Thyroid Association®, September 30 to October 3, 2021.

Background: The anatomic boundaries of lymphadenectomy for adrenocortical carcinoma (ACC) are not defined. Methods: Adults undergoing resection of ACC were included. Locations were categorized based on positive LN locations on final pathology. Results: Of 231 resected ACC, 6% had positive LN during initial resection. Positive LN in left ACC (n = 7) were: 2 para-aortic, 2 left renal-hilar, 1 para-aortic and left renal-hilar and 1 unknown, while for right ACC (n = 7): 2 para-caval, 1 para-caval and right renal-hilar, 1 inter-aortocaval, 1 celiac, 1 para-aortic, and 1 unknown. Of 55 resections for recurrent ACC, positive LN in left ACC (n = 2) were: 1 para-aortic, and 1 para-aortic with left renalhilar, while LN for right ACC (n = 7): 2 inter-aortocaval, 2 right renal-hilar, 2 para-caval and one retrocrural. Conclusion: The most common LN metastases are para-caval for right, and para-aortic and left renal-hilar for left ACC. Further studies are necessary to determine the boundaries of lymphadenectomy in ACC resection.

BACKGROUND:Primary Hyperparathyroidism (PHPT) is rare in pediatric patients. Data regarding surgical outcomes are scarce. METHODS:Single-center retrospective review (1994-2020) of patients ≤21 years undergoing surgery for PHPT. RESULTS:66 patients were identified (61% female, 17 ± 3 years). 71% of patients were symptomatic at diagnosis. 32% of patients had known familial syndromes, most commonly MEN-1. 23% of patients without a known mutation had genetic testing, 22% positive. 56% of the total and 19% of the familial cohort underwent focused exploration. Single gland disease was found in 19% of familial vs 85% of sporadic cases, p < 0.00001. Persistence was 9%, all in the sporadic group, p = 0.11. Recurrence was 15%: 38% in the familial vs 2% in the sporadic groups, p=0.0004. Time to recurrence was 59 months (Q1-38, Q3-95), familial 61 vs 124 months sporadic, p=0.001. CONCLUSION:Pediatric PHPT is frequently sporadic, although 5% of apparent sporadic cases are secondary to syndromes. Familial cases have higher rates of recurrence, requiring closer follow-up.

The authors regret that in the published version of Table V, there were typographical errors in rows 1 and 4. The authors also regret that the version of Supplementary Table 1 in the Supplemental Materials document is incorrect. The corrected version of Table V and Supplementary Table 1 have been included below. The authors wish to apologise for any inconvenience caused.Table VCharacteristics and treatment outcomes of 15 patients diagnosed with NF-PNETs at ≤18 years oldNF-PNET ≤ 18 years (n = 15)Age at MEN1 diagnosis, years, median [range]14 [4 – 17]Sex, female9 (64%)Age at last follow-up, median [range]22 [16 – 27]Age at NF-PNET diagnosis, years, median [range]15 [10 – 18]Imaging modality for diagnosis CT2 (13%) MRI10 (67%) EUS3 (20%)Multifocality7 (47%)Number of tumors on imaging, median [range]1 [1 – 6]Size of largest tumor at diagnosis, mm, median [range]9 [4 - 38]Location of largest tumor on imaging Head/uncinate4 (27%) Body/tail11 (73%)Metastasis at time of diagnosis1 (7%)Surgical resection5 (36%) Age at surgery, median [range]16 [12-20] Number of tumors on pathology, median [range]∗Pathology data were missing for 1 patient.2 [1 – 5] Size of largest tumor on pathology, mm, median [range]∗Pathology data were missing for 1 patient.22 [18 – 40] Tumor gradeG11 (20%)G22 (40%)G31 (20%)Missing1 (20%)Positive lymph nodes on pathology0 Recurrence in pancreatic remnant after surgery2 (40%)Development of metastasis during follow-up1Duration of follow-up, months, median [range]79 [6-131]CT, computed tomography; EUS, endoscopic ultrasound; G, grade; MRI, magnetic resonance imaging; NF-PNET, non-functioning pancreatic neuroendocrine tumor.∗ Pathology data were missing for 1 patient. Open table in a new tab Supplementary Table 1Details of manifestations and germline pathogenic variants in 80 patients with MEN1 from 60 unrelated familiesCase IDFamily IDSexAge at MEN1 diagnosis, yearsNucleotide changeProtein changeVariant typeAge at last F/UManifestation(s) detected at ≤18 yearsManifestation(s) detected at > 18 yearsDuration of F/U (months)11M0.9c.957C>Ap.Tyr319StopNonsense6NoneN/A6822M0.75c.503T>Cp.Leu168ProMissense6NoneN/A7131M5c.957C>Ap.Tyr319StopNonsense10NoneN/A6543F4c.668T>Cp.Leu223ProMissense10NoneN/A7053F7c.668T>Cp.Leu223ProMissense9NoneN/A1462F2c.503T>Cp.Leu168ProMissense13Prolactinoma (11 y.o.)N/A14074F5c.668T>Cp.Leu223ProMissense13PHPT (12 y.o.)N/A9085F5c.1400_1413delp.Ala467GlyfsX59Frameshift13NoneN/A9396F5c.1400_1413delp.Ala467GlyfsX59Frameshift11Prolactinoma (9 y.o.)PHPT (11 y.o.)N/A82107F13c.1262G>Ap.Cys421TyrMissense15PHPT (14 y.o.)N/A22118F15c.959C>Tp.Pro320LeuMissense16PHPT (14 y.o.)N/A24123F6c.668T>Cp.Leu223ProMissense16NoneN/A119139F10c.1A>Cp.Met1ValMissense12NoneN/A231410M14c.776_781dupp.Leu259_Gln260dupIn-frame duplication17PHPT (15 y.o.)NF-PNET (15 y.o.)Prolactinoma (15 y.o.)N/A23154F6c.668T>Cp.Leu223ProMissense18PHPT (15 y.o.)N/A1271611M7c.658T>Cp.Trp220ArgMissense18NF-PA (11 y.o.)PHPT (18 y.o.)N/A1351711M14c.658T>Cp.Trp220ArgMissense25NoneNone1351812F16c.784-9G>Ap.Lys262fsX10Acceptor splice site18PHPT (15 y.o.)N/A151913F15c.1724T>Ap.Ile575AsnMissense22NonePHPT (19 y.o.)NF-PNET (19 y.o.)Prolactinoma (22 y.o.)742014F13UnknownaPatient tested positive for MEN1 germline pathogenic variant but specific variant unknown.UnknownUnknown16PHPT (13 y.o.)NF-PNET (15 y.o.)N/A372115M11c.1643_1721delp.Gly548fsX14Frameshift23PHPT (11 y.o.)NF-PNET (20 y.o.)1502216M14UnknownbGermline variant unknown as family declined genetic testing.UnknownUnknown24NF-PNET (14 y.o.)NF-PA (14 y.o.)None1172317F14UnknownaPatient tested positive for MEN1 germline pathogenic variant but specific variant unknown.UnknownUnknown15PHPT (14 y.o.)Prolactinoma (14 y.o.)N/A122418F16UnknownaPatient tested positive for MEN1 germline pathogenic variant but specific variant unknown.UnknownUnknown22PHPT (16 y.o.)NF-PNET (17 y.o.)Prolactinoma (22 y.o.)662519F16c.654+3A>GN/ADonor splice site27Prolactinoma (16 y.o.)PHPT (19 y.o.)NF-PNET (26 y.o.)1212615M13c.1643_1721delp.Gly548fsX14Frameshift24PHPT (14 y.o.)None1242720F17c.1579C>Tp.Arg527XNonsense23PHPT (18 y.o.)None622816M17UnknowncPatient’s first-degree relative tested positive for MEN1 germline pathogenic variant, but specific variant unknown.UnknownUnknown25PHPT (17 y.o.)NF-PNET (18 y.o.)None922921F16UnknowncPatient’s first-degree relative tested positive for MEN1 germline pathogenic variant, but specific variant unknown.UnknownUnknown26Prolactinoma (16 y.o.)PHPT (17 y.o.o)NFAA (25 y.o.)1093022F13c.495_504delp.Cys165fsX17Frameshift29PHPT (14 y.o.)NF-PNET (27 y.o.)ACTH-oma (27 y.o.)1933123F18c.1243C>Tp.Arg415XNonsense31Prolactinoma (18 y.o.)PHPT (30 y.o.)NF-PNET (30 y.o.)1443224M17c.912+1G>AN/ADonor splice site30PHPT (13 y.o.)GH-oma (19 y.o.)Gastrinoma (22 y.o.)NFAA (30 y.o.)1943325M4c.76G>Tp.Glu26XNonsense32PHPT (7 y.o.)NF-PNET (27 y.o.)306343F14c.668T>Cp.Leu223ProMissense34Prolactinoma (15 y.o.)PHPT (19 y.o.)NF-PNET (22 y.o.)2253523M18c.1243C>Tp.Arg415XNonsense34PHPT (10 y.o.)NF-PNET (19 y.o.)Prolactinoma (20 y.o.)2943626F15c.421C>Tp.Gln141XMissense28Insulinoma (15 y.o.)PHPT (18 y.o.)None1573727M8UnknownaPatient tested positive for MEN1 germline pathogenic variant but specific variant unknown.UnknownUnknown20Prolactinoma (18 y.o.)None1783828F18UnknowncPatient’s first-degree relative tested positive for MEN1 germline pathogenic variant, but specific variant unknown.UnknownUnknown25PHPT (18 y.o.)Insulinoma (19 y.o.)None883929F14c.784-9G>AN/AAcceptor splice site25NonePHPT (20 y.o.)NF-PNET (23 y.o.)1244030F11c.1378C>Tp. Arg460XNonsense27NoneNF-PNET (20 y.o.)834131F17c. 503T>Cp.Leu168ProMissense33NonePHPT (19 y.o.)Prolactinoma (20 y.o.)NF-PNET (23 y.o.)2004232F17UnknownaPatient tested positive for MEN1 germline pathogenic variant but specific variant unknown.UnknownUnknown25PHPT (18 y.o.)None904333F8c.1045C>Tp.Gln349XNonsense23NF-PNET (12 y.o.)Prolactinoma (12 y.o.)Gastrinoma (18 y.o.)Insulinoma (18 y.o.)PHPT (19 y.o.)1894433F4c.1045C>Tp.Gln349XNonsense14Insulinoma (10 y.o.)NF-PNET (10 y.o.)PHPT (10 y.o.)NFAT (10 y.o.)N/A984533M5c.1045C>Tp.Gln349XNonsense8NoneN/A374634F6c.1008dupp.Ala337fsX30Frameshift13Prolactinoma (10 y.o.)PHPT (11 y.o.)N/A584735M2c.549G>Ap.Trp183XNonsense16NoneN/A154836F6c.1204_1208delp.Ser402fsX5Frameshift20Prolactinoma (12 y.o.)PHPT (13 y.o.)NF-PNET (14 y.o.)None1594937F12c.461G>Tp.Ser154IleMissense22NF-PNET (15 y.o.)PHPT (16 y.o.)None805038F2c.202_206dupp.Asp70fsX51Frameshift9NoneN/A835139F15c.668T>Cp.Leu223ProMissense27PHPT (15 y.o.)NF-PNET (17 y.o.)Prolactinoma (17 y.o.)None1465234M8c.1008dupp.Ala337fsX30Frameshift22NF-PNET (16 y.o.)PHPT (17 y.o.)None1295334F6c.1008dupp.Ala337fsX30Frameshift21NF-PNET (14 y.o.)PHPT (16 y.o.)None1145440M17c.1243C>Tp.Arg415XNonsense26PHPT (17 y.o.)NF-PNET (17 y.o.)None1045540M17c.1243C>Tp.Arg415XNonsense28PHPT (17 y.o.)NF-PNET 26 y.o.)1265641F12c.549G>Ap.Trp183XNonsense30PHPT (12 y.o.)NF-PNET (20 y.o.)1485742F18c.461G>Tp.Ser154IleMissense26NonePHPT (23 y.o.)585843M18c.269_270delp.Tyr90fsX26Frameshift29NonePHPT (29 y.o.)1255944M11c.628_631delp.Thr210fsX13Frameshift21NoneNone1036044F14c.628_631delp.Thr210fsX13Frameshift24NF-PNET (16 y.o.)PHPT (22 y.o.)1106141M10c.549G>Ap.Trp183XNonsense35Insulinoma (10 y.o.)NF-PNET (24 y.o.)NFAA (24 y.o.)PHPT (31 y.o.)1356245M13Deletion exon 2N/AGross deletion16PHPT (15 y.o.)N/A336346M11c.784-9G>AN/AAcceptor splice site15Prolactinoma (11 y.o.)PHPT (15 y.o.)N/A456447F3c.535G>Ap.Glu179LysMissense14PHPT (11 y.o.)N/A1396548M7c.292C>Tp.Arg98XNonsense13NoneN/A776647F5c.535G>Ap.Glu179LysMissense6PHPT (6 y.o.)N/A76747F7c.535G>Ap.Glu179LysMissense17NoneN/A1156849M6c.1204_1208delp.Ser402fsX5Frameshift7Insulinoma (6 y.o.)PHPT (6 y.o.)N/A146950M9c.378G>Ap.Trp126XNonsense14NoneN/A677051F16c.628_631delp.Thr210fsX13Frameshift18PHPT (16 y.o.)N/A287152M18c.1075_1077delp.Glu359delIn-frame deletion26PHPT (18 y.o.)Insulinoma (18 y.o.)None1067251F13c.628_631delp.Thr210fsX13Frameshift25PHPT (18 y.o.)NF-PA (19 y.o.)847353M18c.1304delp.Gly435fsX10Frameshift28NoneProlactinoma (22 y.o.)PHPT (22 y.o.)NF-PNET (25 y.o.)707454F15c.1546dupp.Arg516fsX15Frameshift21Prolactinoma (14 y.o.)PHPT (18 y.o.)None707555F16UnknownaPatient tested positive for MEN1 germline pathogenic variant but specific variant unknown.UnknownUnknown25Insulinoma (16 y.o.)PHPT (17 y.o.)None967656F18c.1085delp.Lys362fsX6Frameshift23NoneNF-PNET (22 y.o.)PHPT (22 y.o.)497757F16c.1546dupp.Arg516fsX15Frameshift26PHPT (16 y.o.)None1627858F10UnknownaPatient tested positive for MEN1 germline pathogenic variant but specific variant unknown.UnknownUnknown30NF-PA (18 y.o.)NF-PNET (18 y.o.)PHPT (25 y.o.)1987959F17c.740T>Ap.Ile247AsnMissense18Hyperparathyroidism (16 y.o.)N/A158060M8c.249_252delp.Ile85fsX33Frameshift12Insulinoma (12 y.o.)N/A46ACTH-oma, corticotrophin-secreting pituitary adenoma (corticotrophinoma); GH-oma, growth-hormone secreting pituitary adenoma (somatotrophinoma); F, female; F/U, follow-up; M, male; MEN1, multiple endocrine neoplasia type 1; NF-PNET, non-functioning pancreatic neuroendocrine tumor; NFAA, non-functioning adenal adenoma; NF-PA, non-functioning pituitary adenoma; PHPT, primary hyperparathyroidism.a Patient tested positive for MEN1 germline pathogenic variant but specific variant unknown.b Germline variant unknown as family declined genetic testing.c Patient’s first-degree relative tested positive for MEN1 germline pathogenic variant, but specific variant unknown. Open table in a new tab CT, computed tomography; EUS, endoscopic ultrasound; G, grade; MRI, magnetic resonance imaging; NF-PNET, non-functioning pancreatic neuroendocrine tumor. ACTH-oma, corticotrophin-secreting pituitary adenoma (corticotrophinoma); GH-oma, growth-hormone secreting pituitary adenoma (somatotrophinoma); F, female; F/U, follow-up; M, male; MEN1, multiple endocrine neoplasia type 1; NF-PNET, non-functioning pancreatic neuroendocrine tumor; NFAA, non-functioning adenal adenoma; NF-PA, non-functioning pituitary adenoma; PHPT, primary hyperparathyroidism. Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomesSurgeryVol. 171Issue 1PreviewClinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. Full-Text PDF

Bilateral idiopathic hyperaldosteronism (IHA) is responsible for 60% of primary aldosteronism (PA) cases. Medical management is standard of care for IHA. Unilateral adrenalectomy (UA) with the intent of debulking total aldosterone production as a palliative measure remains controversial. Single-center retrospective review (2010–2020) of patients undergoing UA with a diagnosis of PA due to IHA (lateralization index [LI] on adrenal venous sampling [AVS] < 4). Demographic, pre-operative, intra-operative, and post-operative variables were assessed. Hypertensive regimens were converted to the WHO Defined Daily Dose (DDD). Twenty-four patients were identified, 14, 58% male and mean age 52 ± 10 years. Preoperative hypokalemia was present in 22, 92% of patients. Median number of antihypertensives taken was 3 (interquartile range [IQR], 2–4) and median DDD was 4 (IQR, 3–5.3). Median lateralization index on AVS was 3.52 (range, 1.19–3.88). All operations were performed in minimally invasive fashion. There were no conversions to open procedure, ICU admissions, or post-operative complications. Median follow-up was 10.5 months (range, 1–145 months). Hypokalemia resolved in 17, 76% of patients at last follow-up. Post-operative median number of antihypertensives taken was 1 (IQR, 1–3) and median DDD was 2 (IQR, 0.5–2.75) from 4, P = 0.003. Three (%) patients required continuation of mineralocorticoid receptor antagonists post-operatively. Blood pressure control improved in 65% of patients. Unilateral adrenalectomy in the setting of bilateral hyperaldosteronism can improve blood pressure control and stabilize potassium levels in selected patients. Further prospective studies in larger cohorts will be necessary to further define the role of unilateral adrenalectomy in the setting of PA due to bilateral adrenal disease.