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Edward M Wolin,1 Barbara Jarzab,2 Barbro Eriksson,3 Thomas Walter,4 Christos Toumpanakis,5 Michael A Morse,6 Paola Tomassetti,7 Matthias M Weber,8 David R Fogelman,9 John Ramage,10 Donald Poon,11 Brian Gadbaw,12 Jiang Li,12 Janice L Pasieka,13 Abakar Mahamat,14 Fredrik Swahn,15 John Newell-Price,16 Wasat Mansoor,17 Kjell Öberg3 1Markey Cancer Center, University of Kentucky, Lexington, KY, USA; 2Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland; 3Department of Medical Sciences, Endocrine Oncology Unit, University Hospital, Uppsala, Sweden; 4Department of Medical Oncology, Edouard Herriot Hospital, Lyon, France; 5Gastroenterology and Neuroendocrine Tumours, Royal Free Hospital, London, UK; 6Department of Medical Oncology, Duke University Medical Center, Durham, NC, USA; 7Department of Medical and Surgical Sciences, University Hospital St Orsola, Bologna, Italy; 8Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Mainz, Germany; 9Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA; 10Gastroenterology Unit, North Hampshire Hospital, Basingstoke, UK; 11Department of Medical Oncology, Raffles Hospital and Duke–NUS Graduate Medical School, Singapore; 12Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 13Surgery and Oncology Faculty of Medicine, Foothills Hospital, Calgary, AB, Canada; 14Department of Gastrointestinal Oncology, CHU de Nice Hôpital de l’Archet 1, Nice, France; 15Department of Clinical Science, Intervention and Technology, Karolinska Universitatssjukhuset, Huddinge, Stockholm, Sweden; 16Department of Human Metabolism, School of Medicine and Biomedical Science, The University of Sheffield, and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK; 17Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK Abstract: In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27–1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89–4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 – not reached) with pasireotide versus 6.8 months (5.6 – not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20–0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR. Keywords: neuroendocrine tumors, carcinoid syndrome, somatostatin analogues, pasireotide, symptom control, progression-free survival

Context: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, but the comparative outcomes of targeted treatment remain unclear., Objective: To compare the clinical outcomes in patients treated for primary aldosteronism over time., Methods: Medline and EMBASE were searched. Original studies reporting the incidence of mortality, major adverse cardiovascular outcomes (MACE), progression to chronic kidney disease, or diabetes following adrenalectomy vs medical therapy were selected. Two reviewers independently abstracted data and assessed study quality. Standard meta-analyses were conducted using random-effects models to estimate relative differences. Time to benefit meta-analyses were conducted by fitting Weibull survival curves to estimate absolute risk differences and pooled using random-effects models., Results: 15 541 patients (16 studies) with PA were included. Surgery was consistently associated with an overall lower risk of death (hazard ratio [HR] 0.34, 95% CI 0.22-0.54) and MACE (HR 0.55, 95% CI 0.36-0.84) compared with medical therapy. Surgery was associated with a significantly lower risk of hospitalization for heart failure (HR 0.48 95% CI 0.34-0.70) and progression to chronic kidney disease (HR 0.62 95% CI 0.39-0.98), and nonsignificant reductions in myocardial infarction and stroke. In absolute terms, 200 patients would need to be treated with surgery instead of medical therapy to prevent 1 death after 12.3 (95% CI 3.1-48.7) months., Conclusion: Surgery is associated with lower all-cause mortality and MACE than medical therapy for PA. For most patients, the long-term surgical benefits outweigh the short-term perioperative risks., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Pheochromocytomas produce excess catecholamines that can result in intraoperative hemodynamic instability. Centers have reported variations in intraoperative hemodynamics with the retroperitoneoscopic versus the laparoscopic transperitoneal approach to adrenalectomies. When the retroperitoneoscopic approach was initiated for pheochromocytomas at our institution, the perception was of improved intraoperative hemodynamics, hypothesizing that increased retroperitoneoscopic insufflation pressures caused decreased venous return and less fluctuation in circulating catecholamines. The purpose of this study was to examine if a difference in intraoperative hemodynamics exists between a size-matched cohort of laparoscopic transperitoneal and retroperitoneoscopic pheochromocytoma patients., Methods: Unilateral adrenalectomies for pheochromocytoma performed via laparoscopic transperitoneal or retroperitoneoscopic approaches from 2015 to 2021 were identified from a surgical database. As larger tumors often underwent a laparoscopic transperitoneal approach, cases were matched 1:1 by tumor size. All patients received phenoxybenzamine. Groups were compared by patient characteristics, preoperative blockade, intraoperative hemodynamics and management, and early postoperative outcomes., Results: There were 13 laparoscopic transperitoneal adrenalectomy cases matched to 13 retroperitoneoscopic cases according to tumor size. Both groups (laparoscopic transperitoneal and retroperitoneoscopic) were similar for age (53 years), body mass index (28.5 vs 29.7), sex (69% female), and side (8 vs 7 right). There was no difference in preoperative 24-hour urine metanephrines/normetanephrines (9.9/8.0 vs 2.4/5.7 μmol/day). The phenoxybenzamine dose was similar in both groups (112 vs 114 mg/24 hours), as were baseline heart rate, blood pressure, and mean arterial pressure. There was no difference in any intraoperative hemodynamic parameters or vasoactive interventions. Operative time, length of stay, and 30-day emergency visits were similar between groups., Conclusion: This matched cohort study did not find a difference in intraoperative hemodynamics between laparoscopic transperitoneal and retroperitoneoscopic adrenalectomy approaches for pheochromocytoma in appropriately selected and blocked patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans., Methods: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon., Results: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ 2  = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66)., Conclusion: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness on affected patients and their caregivers contributes to reduced quality of life and social costs for this chronic endocrinopathy. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

This clinical practice guideline addresses the prevention, diagnosis, and management of hypoparathyroidism (HypoPT) and provides evidence-based recommendations. The HypoPT task forces included four teams with a total of 50 international experts including representatives from the sponsoring societies. A methodologist (GG) and his team supported the taskforces and conducted the systematic reviews. A formal process following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and the systematic reviews provided the structure for seven of the guideline recommendations. The task force used a less structured approach based on narrative reviews for 20 non-GRADEd recommendations. Clinicians may consider postsurgical HypoPT permanent if it persists for >12 months after surgery. To predict which patients will not develop permanent postsurgical HypoPT, we recommend evaluating serum PTH within 12 to 24 hours post total thyroidectomy (strong recommendation, moderate quality evidence). PTH > 10 pg/mL (1.05 pmol/L) virtually excludes long-term HypoPT. In individuals with nonsurgical HypoPT, genetic testing may be helpful in the presence of a positive family history of nonsurgical HypoPT, in the presence of syndromic features, or in individuals younger than 40 years. HypoPT can be associated with complications, including nephrocalcinosis, nephrolithiasis, renal insufficiency, cataracts, seizures, cardiac arrhythmias, ischemic heart disease, depression, and an increased risk of infection. Minimizing complications of HypoPT requires careful evaluation and close monitoring of laboratory indices. In patients with chronic HypoPT, the panel suggests conventional therapy with calcium and active vitamin D metabolites as first-line therapy (weak recommendation, low-quality evidence). When conventional therapy is deemed unsatisfactory, the panel considers the use of PTH. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Objective: To present clinical outcomes of the prospective implementation of the 2015 American Thyroid Association (ATA) guidelines for the management of thyroid nodules and differentiated thyroid cancer (DTC) using the modified ATA recurrence risk (RR) stratification system. Methods: We prospectively analyzed 612 patients with DTC treated between April 2017 and December 2021 in Calgary, Alberta. Each patient was prospectively assigned a modified ATA RR and American Joint Committee Cancer 8th edition stage. Initial risk stratification and consideration of the 2015 ATA guidelines guided surgical management as well as the indication for and dose of radioiodine (RAI) and other adjuvant therapies. Patients were assessed for their response to treatment (RTT) at 2-years postoperatively. Results: There were 479 patients who had 2-year follow-up data and were included in the study. Of these patients, there were 253 (53%) low-, 129 (27%) intermediate-, and 97 (20%) high-RR patients. Of these, 227 patients (47%) underwent total thyroidectomy (TTX) plus RAI, 178 (37%) underwent TTX only, and 74 (16%) underwent lobectomy. The RTT at 2 years was excellent for 89% (66) of patients with lobectomy, 84% (149) for TTX only, and 53% (121) for TTX plus RAI. Among 253 patients who were deemed low RR, 85% (216) had excellent RTT, 13% (32) indeterminate RTT, 2% (4) biochemical incomplete RTT, and 1 patient had structural incomplete RTT. The intermediate RR group had the following RTT outcomes: 64% (83) excellent, 23% (30) indeterminate, 6% (7) biochemical incomplete, and 7% (9) structural incomplete. The high RR group had the worst RTT outcomes, with 38% (37) excellent, 19% (18) indeterminate, 10% (10) biochemical incomplete, and 33% (32) structural incomplete RTT. Conclusions: The 2015 ATA RR stratification system is useful for predicting disease status at 2-year post-treatment in patients with DTC. The 2015 ATA guidelines and modified ATA RR stratification treatment recommendations may reduce thyroid cancer overtreatment by including lobectomy as a definitive treatment option for low-risk thyroid cancers and selective use of RAI for intermediate and high-risk patients.

Introduction: Minimally invasive adrenalectomy includes laparoscopic transperitoneal (LA) and retroperitoneoscopic (RP) approaches. This study reviewed the local adrenalectomy practice to identify characteristics and outcomes between patients undergoing adrenalectomy via LA, RP, and RP requiring conversion (RPC)., Methods: Adrenalectomies documented in a prospective surgical database were reviewed. Demographics, diagnosis, surgical approach/conversion, body mass index (BMI), radiographic body measurements (RBM), tumor size, operative time (OT), length of stay (LOS), and 30-day post-operative emergency (ED) visits were collected., Results: 203 adrenalectomies were reviewed from 2015 to 2020. The RP group had the shortest OT (124 ± 54 min, p = 0.281 vs LA, p < 0.001 vs RPC) and LOS (1.6 ± 1.0 days, p < 0.001 vs LA and RPC). There was an 18% conversion rate from RP to LA, and in one case to laparotomy. The RPC group had greater BMI, OT, LOS, and ED visits than LA and RP. The RPC group had less favorable RBM (p < 0.001). On multivariate analysis, RBM impacted OT, LOS, and ED visits (p < 0.05)., Discussion: The RP approach had shorter OT and LOS. BMI and RBM may increase risk of conversion, OT, LOS, and ED visits. Preoperative RBM may aid in appropriate patient selection for a RP approach., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear., Methods: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models., Results: Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46-21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48-17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low., Conclusions: Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered.

Background: Targeted treatment of primary aldosteronism (PA) is informed by adrenal vein sampling (AVS), which remains limited to specialized centers. Clinical prediction models have been developed to help select patients who would most likely benefit from AVS. Our aim was to assess the performance of these models for PA subtyping., Methods: This external validation study evaluated consecutive patients referred for PA who underwent AVS at a tertiary care referral center in Alberta, Canada during 2006-2018. In alignment with the original study designs and intended uses of the clinical prediction models, the primary outcome was the presence of lateralization on AVS. Model discrimination was evaluated using the C-statistic. Model calibration was assessed by comparing the observed vs. predicted probability of lateralization in the external validation cohort., Results: The validation cohort included 342 PA patients who underwent AVS (mean age, 52.1 years [SD, 11.5]; 201 [58.8%] male; 186 [54.4%] with lateralization). Six published models were assessed. All models demonstrated low-to-moderate discrimination in the validation set (C-statistics; range, 0.60-0.72), representing a marked decrease compared with the derivation sets (range, 0.80-0.87). Comparison of observed and predicted probabilities of unilateral PA revealed significant miscalibration. Calibration-in-the-large for every model was >0 (range, 0.35-1.67), signifying systematic underprediction of lateralizing disease. Calibration slopes were consistently <1 (range, 0.35-0.87), indicating poor performance at the extremes of risk., Conclusions: Overall, clinical prediction models did not accurately predict AVS lateralization in this large cohort. These models cannot be reliably used to inform the decision to pursue AVS for most patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Background: This study investigates the impact of the COVID-19 pandemic on endocrine surgeons., Methods: A survey on the professional, educational, and clinical impact was sent to active and corresponding members of the American Association of Endocrine Surgeons (AAES) in September 2020. Chi-square and paired t-test were used for analysis., Results: 77 surgeons responded (14.8 %). All reported suspension of elective surgeries; 37.7 % were reassigned to other duties during this time. The median number of cases backlogged was 30 (IQR 15-50). Most surgeons reported decreased clinical volume (74.6 %). The use of virtual platforms for clinical and educational purposes increased from pre-COVID-19 levels (all p < 0.001). Use of in-office procedures (p < 0.001) and length of observation prior to discharge for thyroid surgery (p < 0.05) decreased., Conclusion: The COVID-19 pandemic led to suspension of operations and decreased practice volume for endocrine surgeons. Surgeons increased use of virtual platforms, decreased in-office procedures, and decreased duration of observation for thyroid surgery in response., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Summary: An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC)/paraganglioma is the cause of ectopic Cushing's syndrome (CS) in 5.2% of cases reported in the literature. We present a previously healthy 43-year-old woman admitted to our hospital with cushingoid features and hypertensive urgency (blood pressure = 200/120 mmHg). Her 24-h urinary free cortisol was >4270 nmol/day (reference range (RR) = 100-380 nmol/day) with a plasma ACTH of 91.5 pmol/L (RR: 2.0-11.5 pmol/L). Twenty-four-hour urinary metanephrines were increased by 30-fold. Whole-body CT demonstrated a 3.7-cm left adrenal mass with a normal-appearing right adrenal gland. Sellar MRI showed a 5-mm sellar lesion. MIBG scan revealed intense uptake only in the left adrenal mass. She was managed pre-operatively with ketoconazole and phenoxybenzamine and underwent an uneventful left laparoscopic adrenalectomy, which resulted in biochemical resolution of her hypercortisolemia and catecholamine excess. Histology demonstrated a PCC (Grading System for Adrenal Pheochromocytoma and Paraganglioma score 5) with positive ACTH staining by immunohistochemistry. A PCC gene panel showed no mutations and there has been no evidence of recurrence at 24 months. This case highlights the difficult nature of localizing the source of CS in the setting of a co-existing PCC and sellar mass., Learning Points: An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC) is an important item to be considered in all patients presenting with ectopic Cushing's syndrome (CS). In exceptionally rare cases, patients with ectopic CS may present with multiple lesions, and a systematic approach considering all potential sources is crucial to avoid misdiagnosis. CS with a large adrenal mass but lacking contralateral adrenal atrophy should raise suspicion of an ACTH-dependent process. In patients with clinical suspicion of PCC, clinicians should be mindful of the use of steroids and beta-blockers without appropriate alpha blockade as they may precipitate an adrenergic crisis.

Objective: We previously highlighted the problem of frequent false positives in 24 h urine normetanephrine(UNM) measurements owing to reference intervals that are inappropriately low for the population being screened for pheochromocytoma. Using a large population database, we devised new age-stratified reference intervals for the 24 h UNM test that were higher compared to previous. However, it was uncertain as to whether this would compromise test sensitivity for true pheochromocytoma cases., Design and Methods: Retrospective analysis of all pheochromocytoma cases from a recently constructed provincial registry. All confirmed cases had their diagnostic UNM results retrospectively re-analysed according to the newly proposed UNM reference intervals to determine the percentage and phenotype of cases that might have been theoretically missed with the new reference range., Results: After excluding pediatric and non-secretory head and neck paragangliomas, there were 60 confirmed pheochromocytoma cases. Using prior reference intervals, 51/60 (85%) had an abnormally high UNM. Of the 9 with normal UNM, 4 had a high urine metanephrine(UMN), 5 had normal levels of both UNM and UMN such that 55/60 had abnormal test results, representing the historical combined test sensitivity of 92%. Using the proposed reference interval, 43/60 (72%) had high UNM results. Of the 17 with normal UNM, 12 had high UMN, 5 had normal levels of both UNM and UMN. Therefore, 55/60 patients had had elevations in either UNM or UMN, corresponding to an identical combined test sensitivity of 92%., Conclusions: Reference intervals for UNM derived from actual clinical population screening data are higher than in traditional healthy volunteers. Use of these more appropriate reference intervals can significantly reduce the false positive rate without compromising test sensitivity for true pheochromocytoma., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Context: False-positive results are common for pheochromocytoma/paraganglioma (PPGL) real-world screening., Objective: Determine the correlation between screening urine and seated plasma metanephrines in outpatients where PPGL was absent, compared to meticulously prepared and supine-collected plasma metanephrines with age-adjusted references., Design: Retrospective cohort study., Setting: Databases from a single-provider provincial laboratory (2012-2018), a validated PPGL registry, and a manual chart review from a specialized endocrine testing unit., Patients: PPGL registry data excluded known PPGL cases from the laboratory database. Outpatients having both urine and plasma metanephrines <90 days apart., Methods: The correlation between urine and seated plasma measures along with the total positivity rate. All cases of plasma metanephrines drawn in the endocrine unit were reviewed for test indication and test positivity rate., Results: There were 810 non-PPGL pairs of urine and plasma metanephrines in the laboratory database; 46.1% of urine metanephrines were reported high. Of seated outpatient plasma metanephrines drawn a median of 5.9 days later, 19.2% were also high (r = 0.33 and 0.50 for normetanephrine and metanephrine, respectively). In contrast, the meticulously prepared and supine collected patients (n = 139, 51% prior high urine metanephrines) had <3% rate of abnormal high results in patients without known PPGL/adrenal mass., Conclusions: There was a poor-to-moderate correlation between urine and seated plasma metanephrines. Up to 20% of those with high urine measures also had high seated plasma metanephrines in the absence of PPGL. Properly prepared and collected supine plasma metanephrines had a false-positive rate of <3% in the absence of known PPGL/adrenal mass., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension but remains largely unrecognized and untreated., Objective: To understand the outcomes of a specialized clinic on rates of evaluation and treatment of PA in the context of secondary factors., Design, Setting, and Participants: This population-based cohort study was conducted in Alberta, Canada, using linked administrative data between April 1, 2012, and July 31, 2019, on adults identified as having hypertension., Main Outcomes and Measures: We evaluated each step of the diagnostic and care pathway for PA to determine the proportion of people with hypertension who received screening, subtyping, and targeted treatment for PA. Variations in diagnosis and treatment were examined according to individual-level, clinician-level, and system-level characteristics., Results: Of the 1.1 million adults with hypertension, 7941 people (0.7%) were screened for PA. Among those who were screened, 1703 (21.4%) had positive test results consistent with possible PA, and 1005 (59.0%) of these were further investigated to distinguish between unilateral and bilateral forms of PA. Only 731 individuals (42.9%) with a positive screen result received disease-targeted treatment. Geographic zones and clinician specialty were the strongest determinants of screening, subtyping, and treatment of PA, with the highest rates corresponding to the location of the provincial endocrine hypertension program., Conclusions and Relevance: In this cohort, less than 1% of patients expected to have PA were ever formally diagnosed and treated. These findings suggest that a system-level approach to assist with investigation and treatment of PA may be highly effective in closing care gaps and improving clinical outcomes.

Background: Preoperative localization plays an important role in primary hyperparathyroidism. Sestamibi scans read by the radiologist as nonlocalizing were localizing when independently interpreted by the surgeon. The ability to perform dynamic surgeon-directed imaging, a of combination scans interpreted by the surgeon and surgeon-performed ultrasound done in tandem, appeared to improve preoperative localization. The objective was to evaluate scans read by the radiologist compared with dynamic surgeon-directed imaging., Methods: A retrospective chart review was performed. Demographics, biochemistry, radiologist read scans, dynamic surgeon-directed imaging, operation, pathology, and follow-up results were collected. Localization rate, sensitivity, positive predictive value, and accuracy were calculated., Results: In the study, 474 charts met inclusion criteria. Only 63% of scans read by the radiologist were localizing, compared with 96% of dynamic surgeon-directed imaging. Overall dynamic surgeon-directed imaging was superior to scans read by the radiologist with 95% versus 60% sensitivity, 85% versus 85% positive predictive value, and 82% versus 54% accuracy. Dynamic surgeon-directed imaging remained superior when analyzing only those with single gland disease (n = 391). In addition, 85% of the 174 nonlocalized radiologist scans were correctly localized by dynamic surgeon-directed imaging., Conclusion: The ability to perform an interpretation of both surgeon-performed ultrasound and scan interpreted by the surgeon in tandem improves the preoperative localization rate when compared with static reading of radiologist scans. This underscores the importance of having all primary hyperparathyroidism patients assessed by an experienced parathyroid surgical team, especially when the scans read by the radiologist is nonlocalizing., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: Many patients with unilateral primary aldosteronism (PA) have normal adrenal imaging, but little is known about their outcome following adrenalectomy., Objective: To evaluate biochemical and clinical outcomes after adrenalectomy in patients with unilateral PA and normal-appearing adrenal imaging., Design: Retrospective cohort study of patients seen between January 2006 and May 2018., Setting: A Canadian tertiary care PA referral center., Patients: Consecutive individuals with PA, normal cross-sectional adrenal imaging, and lateralizing adrenal vein sampling (AVS) who underwent adrenalectomy during the study period., Primary Outcome: Biochemical response to adrenalectomy graded according to the Primary Aldosteronism Surgical Outcome criteria., Results: A total of 40 patients were included. Biochemical outcomes were available for 33 people (mean age, 54.7 years; 91% male; median follow-up, 2.7 months), with 28 (85%) showing a complete or partial response and 5 (15%) with no response. Clinical outcomes were available for 36 people (mean age, 54.6 years; 86% male; median follow-up, 9.8 months), with 31 (86%) demonstrating a complete or partial response and 5 (14%) with no response., Conclusions: The prognosis after adrenalectomy is highly favorable for patients with unilateral PA and normal-appearing adrenal imaging. Patients with lateralizing disease should be considered for surgery despite apparently normal adrenal imaging., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In contemporary surgical series, the incidence of multifocal tumours (MFT) in small bowel neuroendrocrine tumours (SBNET) is as high as 50%. Familial forms of SBNET appear to have an even higher rate of MFTs in the range of 80%. Multifocal disease poses several challenges and questions for the operating surgeon, including the cause of the disease whether it is local metastases or a genetic field defect, the extent of the resection, and the prognosis. The etiology of these multiple tumours appears to be multifactorial and may represent localized metastases in some, a genetic mutation resulting in the rare familial form of this disease in others, or the integration of genetic and epigenetic events within the bowel. Contrary to historical series, recent data suggest that MFT are not associated with a poorer prognosis. The challenge remains on the long-term surveillance of these unique tumours.

Background: Classification of thyroid follicular neoplasms can be challenging for pathologists. Introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features, the utilization of immunohistochemistry, and molecular analysis are all thought to be valuable diagnostic adjuncts. Our aim was to determine whether interobserver variability for follicular neoplasms has improved since the application of these adjuncts., Methods: One representative section from a cohort of follicular neoplasms previously proven difficult for pathologists were examined independently by 7 pathologists and assigned to 1 of 3 diagnostic categories (benign, neoplasms with papillary-like nuclear features, or malignant). This process was carried out separately 3 times: (1) after viewing hematoxylin and eosin stain slides, (2) hematoxylin and eosin stain in conjunction with immunohistochemistry, and (3) hematoxylin and eosin stain/immunohistochemistry in conjunction with molecular analysis. The interobserver variability and overall agreement were then calculated using the free-marginal kappa coefficient., Results: Agreement on hematoxylin and eosin stain was 57%, with a kappa coefficient of 0.36 (minimal agreement). The agreement improved slightly with the application of immunohistochemistry (kappa coefficient = 0.49 [weak agreement] and a percentage agreement 67%). The level of agreement decreased slightly after the addition of molecular analysis (kappa coefficient = 0.43 [weak agreement] and percentage agreement 62%)., Conclusion: Despite attempts to standardize the diagnostic criteria for neoplasms with papillary-like nuclear features and the utilization immunohistochemistry and molecular analysis, attaining pathologic consensus for difficult follicular neoplasms of the thyroid remains a challenge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. A secondary objective was to develop and validate algorithms for case detection using laboratory and administrative data., Design: Population-based cohort study in Alberta, Canada from 2012 to 2019., Methods: Patients with pheochromocytoma or paraganglioma were identified using linked administrative databases and clinical records. Annual incidence rates per 100 000 people were calculated and stratified according to age and sex. Algorithms to identify pheochromocytoma and paraganglioma, based on laboratory and administrative data, were evaluated., Results: A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60-79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). An algorithm based on laboratory data (metanephrine >two-fold or normetanephrine >three-fold higher than the upper limit of normal) closely approximated the true frequency of pheochromocytoma and paraganglioma with an estimated incidence of 0.54 cases per 100 000 people per year., Conslusion: The incidence of pheochromocytoma and paraganglioma in an unselected population of western Canada was unexpectedly higher than rates reported from other areas of the world.

Background: The extent of initial surgical resection for low-risk papillary thyroid cancer (PTC) remains debatable. Since the 2015 American Thyroid Association (ATA) guidelines, several retrospective studies have reported that 40-60% of patients initially treated with lobectomy would require a completion thyroidectomy (CTx) due to high-risk pathological features (HRFs). These studies are limited by variable preoperative stratification and inability to quantify the value of intraoperative assessment. The study objectives were to determine whether diligent preoperative and intraoperative assessment improves the appropriateness of initial surgery for low-risk PTCs and whether varying the criteria for lobectomy reduces the need for CTx. Methods: A prospectively collected province-wide database was analyzed over a 10-year period (2008-2017) for patients who underwent a total thyroidectomy (TT) for PTC without preoperative HRFs. All patients had preoperative ultrasound and fine-needle aspirates. Unique to this database are mandatory synoptic operative fields that identify intraoperative risk factors such as positive lymph nodes and local invasion. Results: In total, 74% of patients (709/959) were deemed eligible for lobectomy. Of those eligible, 149 (21%) had intraoperative risk factors that would necessitate conversion to TT at the initial operation. A further 209 (30%) would require CTx due to HRFs on final pathology. Varying the preoperative criteria for lobectomy did not significantly affect intraoperative conversion or CTx rates. Conclusions: Although intraoperative assessment reduced the need for CTx in 21%, up to 30% of patients would still require a second operation. Altering the preoperative criteria does not influence this outcome. Patients deemed eligible for lobectomy should be informed that despite careful pre- and intraoperative assessment, there is up to a 30% risk of requiring CTx.

Innovation can be variably defined, but when applied to healthcare is often considered to be the introduction of something new, whether an idea, method or device, into an unfilled void or needy environment. Despite the introduction of many positive surgical subspecialty altering concepts/devices however, epic failures are not uncommon. These failures can be dramatic in regards to both their human and economic costs. They can also be very public or more quiet in nature. As surgical leaders in our communities and advocates for patient safety and outcomes, it remains crucial that we meet new introductions in technology and patient care with a measured level of curiosity, skepticism and science-based conclusions. The aim of an expert committee was to identify the most dominant failures in technological innovation and/or dogmatic clinical beliefs within each major surgical subspecialty. In summary, this effort was pursued to highlight the past failures and remind surgeons to remain vigilant and appropriately skeptical with regard to the introduction of new innovations and clinical beliefs within our craft.

Objectives: Adrenal vein sampling (AVS) is intended to confirm unilateral forms of primary aldosteronism, which are amenable to surgical cure. Excessively strict AVS criteria to define lateralization may result in many patients incorrectly categorized as bilateral primary aldosteronism and opportunity for surgical cure missed., Methods: Retrospective review of an AVS-primary aldosteronism database in which surgical cases are verified by standardized outcomes. Having used 'less strict' AVS criteria for lateralization, we examined the distribution of AVS lateralization indices in our confirmed unilateral primary aldosteronism cases both with and without cosyntropin stimulation. The proportion of proven unilateral cases that would have been missed with stricter AVS interpretation criteria was calculated. Particular focus was given to the proportion of missed cases according to use of international guidelines. False-positive lateralization with 'less strict' interpretation was also calculated., Results: Of 80 surgical primary aldosteronism cases, 10-23% would have been missed with AVS lateralization indices of 3 : 1 to 5 : 1, with or without cosyntropin. If strict selectivity indices (for confirmation of catheterization) were combined with strict lateralization indices, up to 70% of unilateral primary aldosteronism cases could have been missed. Use of Endocrine Society AVS guidelines would have missed 21-43% of proven unilateral cases. 'Less strict' AVS interpretation yielded one case (1.2%) of false lateralization., Conclusion: Excessively strict AVS interpretation criteria will result in a high rate of missed unilateral primary aldosteronism with subsequent loss of opportunity for intervention. Use of more lenient lateralization criteria will improve the detection rate of unilateral primary aldosteronism with very low false-positive rate.

Introduction: In patients with primary aldosteronism (PA), adrenal venous sampling (AVS) is recommended to differentiate between unilateral (UNI) or bilateral (BIL) adrenal disease. A recent study suggested that lateralization could be predicted, based on the ratio of aldosterone/cortisol levels (A/C) between the left adrenal vein (LAV) and inferior vena cava (IVC), with a 100% positive predictive value (PPV). This study aimed to validate those findings utilizing a larger, multi-institutional cohort., Methods: A retrospective review was performed of patients with PA who underwent AVS from 2 tertiary-care institutions. Laterality was predicted by an A/C ratio of >3:1 between the dominant and non-dominant adrenal. AVS results were compared to LAV/IVC ratios utilizing the published criteria (Lt ≥ 5.5; Rt ≤ 0.5)., Results: Of 222 patients, 124 (57%) had UNI and 98 (43%) had BIL disease based on AVS. AVS and LAV/IVC findings were concordant for laterality in 141 (64%) patients (69 UNI, 72 BIL). Using only the LAV/IVC ratio, 54 (24%) patients with UNI disease on AVS who underwent successful surgery would have been assumed to have BAH unless AVS was repeated, and 24 (11%) patients with BIL disease on AVS may have been incorrectly offered surgery (PPV 70%). Based on median LAV/IVC ratios (left 5.26; right 0.31; BIL 2.84), no LAV/IVC ratio accurately predicted laterality., Discussion: This multi-institutional study of patients with both UNI and BIL PA failed to validate the previously reported PPV of LAV/IVC ratio for lateralization. Caution should be used in interpreting incomplete AVS data to differentiate between UNI versus BIL disease and strong consideration given to repeat AVS prior to adrenalectomy.

Background: Indications for performing a prophylactic central neck dissection (pCND) in papillary thyroid cancer (PTC) remain controversial. It is unclear how identification of lymph node (LN) metastases should impact the decision to treat with radioactive iodine (RAI). The goals of this study were to identify indications for performing pCND and identify factors that predict the use of adjuvant RAI., Methods: This was a population based cross-sectional analysis. A prospectively collected database identified 594 patients who underwent total thyroidectomy +/- CND. A multivariate model was constructed to identify indications for pCND and predictors of the use of RAI., Results: 425 CNDs were performed of which 224 were prophylactic. Conventional risk factors (age, tumor size, extra-thyroidal extension) were not associated with performing a pCND. The presence of clinically suspicious lymphadenopathy was the only factor associated with performing CND, thus rendering the CND therapeutic. Positive LNs were retrieved in 39 % of pCND's, upstaging 87 patients. Among all peri-operative predictors of receiving RAI, presence of LN metastases was the strongest predictor [OR = 5.9 (3.7-9.5)], while tumor size was a modest predictor [OR = 1.8 (1.5-2.1)]. Other conventional risk factors did not predict use of adjuvant RAI., Conclusions: Conventional risk factors were not indications for performing a pCND, implying that the decision was based on individual surgeon preference. Performing pCND upstaged 39 % of patients from cN0 to pN1a, increasing the likelihood of receiving RAI 6-fold. Conventional risk factors were not predictors of receiving adjuvant RAI. This highlights the need for a unified approach to performing a pCND and administering RAI.

Importance: Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades., Objective: To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy., Evidence Review: A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus., Findings: Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise., Conclusions and Relevance: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.

Background: It is unclear if surgeons are performing comprehensive central neck dissections for well-differentiated thyroid cancer. The purpose of this study was to determine mean lymph node retrieval in central neck dissection as well as variability across surgeons and institutions., Methods: A prospectively collected database identified 18 surgeons performing 425 central neck dissections, 313 unilateral and 112 bilateral. Demographics, perioperative, and pathologic factors were analyzed., Results: Mean lymph node yield was 7.4 and 11.9 for unilateral and bilateral central neck dissection, respectively. Although 224 central neck dissections were prophylactic, both total and pathologic lymph node yields were significantly higher in therapeutic central neck dissection. There was a significant variation in lymph node yield across individual surgeons, institutions, and regions. High-volume central neck dissection surgeons have significantly lower lymph node yield compared to low-volume surgeons., Conclusion: Central neck dissection seems to be performed adequately; however, there is a significant variation in lymph node yield. Future initiatives should try to standardize the central neck dissections performed, with emphasis on obtaining a sufficient yield. © 2015 Wiley Periodicals, Inc. Head Neck 38: E328-E332, 2016., (© 2015 Wiley Periodicals, Inc.)

Follicular cell-derived thyroid cancers are derived from the follicular cells in the thyroid gland, which secrete the iodine-containing thyroid hormones. Follicular cell-derived thyroid cancers can be classified into papillary thyroid cancer (80-85%), follicular thyroid cancer (10-15%), poorly differentiated thyroid cancer (<2%) and undifferentiated (anaplastic) thyroid cancer (<2%), and these have an excellent prognosis with the exception of undifferentiated thyroid cancer. The advent and expansion of advanced diagnostic techniques has driven and continues to drive the epidemic of occult papillary thyroid cancer, owing to overdiagnosis of clinically irrelevant nodules. This transformation of the thyroid cancer landscape at molecular and clinical levels calls for the modification of management strategies towards personalized medicine based on individual risk assessment to deliver the most effective but least aggressive treatment. In thyroid cancer surgery, for instance, injuries to structures outside the thyroid gland, such as the recurrent laryngeal nerve in 2-5% of surgeries or the parathyroid glands in 5-10% of surgeries, negatively affect quality of life more than loss of the expendable thyroid gland. Furthermore, the risks associated with radioiodine ablation may outweigh the risks of persistent or recurrent disease and disease-specific mortality. Improvement in the health-related quality of life of survivors of follicular cell-derived thyroid cancer, which is decreased despite the generally favourable outcome, hinges on early tumour detection and minimization of treatment-related sequelae. Future opportunities include more widespread adoption of molecular and clinical risk stratification and identification of actionable targets for individualized therapies.

Objective: Unilateral primary aldosteronism (PA) should have a contralaterally normal and therefore suppressed adrenal zona glomerulosa. However, there is no validated definition of adrenal suppression. We created two biochemical hypotheses of adrenal suppression based upon measurements taken during adrenal vein sampling (AVS) to determine whether either proved useful for interpretation of AVS or prediction of hypertension outcome in operated cases., Design: Retrospective database analysis., Patients: Ninety-nine cases of PA from a tertiary hypertension unit., Measurements: Hypothesis 1 was the proportional suppression of the uninvolved/lowest adrenal(aldo/cortisol) to IVC(aldo/cortisol) ratio pre- and post cosyntropin. Hypothesis 2 was the absolute decrease in the uninvolved adrenal(aldo/cortisol) ratio after cortrosyn injection. ROC analysis performed using lateralization and hypertension resolution as the outcomes of interest., Results: Hypothesis 1 proved highly predictive of lateralization with a ROC AUC of 0.958, P < 0.0001, giving adrenal(aldo/cortisol):IVC(aldo/cortisol) <1.4 as the optimized criterion (sensitivity 90%, specificity 94%). For blood pressure outcomes in the surgical subgroup (n = 52), hypertension resolution was most commonly seen among subjects with adrenal suppression by both definitions although there was significant overlap with subjects requiring ongoing medication., Conclusions: Post cosyntropin suppression of the uninvolved adrenal-to-IVC ratio is a highly useful definition of adrenal suppression that accurately predicts unilateral PA. This may be particularly useful in a case where AVS fails to catheterize one of the adrenal veins but suppression is seen on the other side. Adrenal suppression may also predict blood pressure outcome, however, a much larger PA database is likely necessary to determine the relative contribution of this predictor., (© 2015 John Wiley & Sons Ltd.)

Background: A published clinical prediction score indicated that a unilateral adrenal adenoma and either hypokalemia or an estimated glomerular filtration rate of 100 ml/min/1.73 m2 was 100% specific for unilateral primary aldosteronism. This study aimed to validate this score in a separate cohort of patients with primary aldosteronism., Methods: A review of patients with primary aldosteronism from June 2005 to July 2013 at a single center's hypertension clinic. One hundred twelve patients with primary aldosteronism underwent successful adrenal vein sampling and the 110 patients with full data available were included in the final analysis. Adrenal vein sampling was performed all patients desiring surgery by the simultaneous collection of sample prior to and 15 minutes after a cosyntropin infusion with a 3:1 aldosterone/cortisol ratio diagnosing unilateral primary aldosteronism. The derived score was applied to the cohort. Sensitivity and specificity were calculated for clinical prediction score of ≥5 points., Results: There were 64 patients found to have unilateral primary aldosteronism and 48 had bilateral disease. A score ≥5 points had 64% sensitivity (95% confidence interval, 51-76) and 85% specificity (95% confidence interval, 71-94) for unilateral disease. Four patients had lateralization of primary aldosteronism to the side contralateral to the adenoma., Conclusions: The 100% specificity of the score for the unilateral origin of primary aldosteronism was not validated in this cohort with a score of ≥5 points. At best, a high score in this prediction rule may be an additional tool for helping to confirm a decision to offer patients adrenal vein sampling.

Background: Endocrine surgery is a specialty that is evolving constantly. In this study, we sought to delineate the practice patterns of surgeons taking care of endocrine diseases in present-day academic centers., Methods: A review of the Faculty Practice Solutions Center database was conducted for the years 2005, 2009, and 2013. Practice patterns were determined by International Classification of Diseases, 9th Revision and Current Procedural Terminology codes, and analyzed for practice composition, regional variability, and volume of endocrine operations., Results: Of 97 national academic centers, 52 were identified to have 120 practicing American Association of Endocrine Surgeons (AAES) surgeons in the study. On average, endocrine operations comprise ∼65% of the AAES surgeon's practice, and 51% are considered high-volume surgeons for thyroidectomy, parathyroidectomy, and adrenalectomy. Most non-AAES surgeons who perform endocrine operations are otolaryngologists (24.5%) and other general surgeons (18.5%). Overall, non-AAES surgeons perform the majority of endocrine operations at academic institutions (61.6%), and low-volume surgeons perform most of these operations (55.6%)., Conclusion: Research has shown that high-volume surgeons have improved outcomes. Even in academia, however, the majority of endocrine operations are performed by low-volume surgeons, suggesting that there is an opportunity for expanding the number of surgeons with expertise in endocrine surgery in present-day academic centers., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Computed tomography (CT) of the adrenals is a common first step for investigation of primary aldosteronism (PA). However, prior studies report poor specificity, necessitating adrenal vein sampling (AVS) prior to surgical consideration., Methods: We examined our AVS database to determine whether CT adrenal findings could help select patients with a high likelihood of lateralization by AVS or high-value blood pressure (BP) outcomes. Subjects (N = 113) with validated outcomes were divided into groups of CT 'positive' or CT 'negative' according to the presence or absence of an adrenal mass and compared for the outcomes of lateralization by AVS or proportions achieving normotension off medications following surgery., Results: For patients with CT adrenal masses, there was a significantly higher odds ratio (OR) for both outcomes (6.3 and 9.7, p < 0.01). In subgroup analysis, age <40 years carried particularly high odds for lateralization and cure when a CT mass was present (ORs 45 and 26, p < 0.01). Young individuals with normal CT adrenals rarely lateralized (10 %) and, in such patients, even factors like hypokalemia, body mass index (BMI), and plasma aldosterone level did not change the result on regression analysis., Conclusions: CT-imaged adrenal masses strongly predicted lateralization by AVS and normotension with surgical treatment of lateralized PA. In PA, CT-positive patients should indeed be offered AVS and/or surgery given the high chance of good outcomes; younger CT-negative patients should be advised of a low chance of finding surgical disease by AVS.

This retrospective review examined all primary aldosteronism (PA) adrenal vein sampling (AVS), diagnoses, and outcomes from an endocrine hypertension unit where confirmatory testing was abandoned in 2005 to determine the potential rate of false-positive diagnoses. Patients with outcome-verified PA (surgical patients) were compared with patients with high-probability PA (nonsurgical but high aldosterone-renin ratio, imaging abnormalities, and/or hypokalemia) or possible PA (nonsurgical, no features besides mild elevation of aldosterone-renin ratio, a potential false diagnosis of PA). Of 83 patients, 58% had unilateral PA and 42% had bilateral aldosteronism. Less than 3% of the cohort showed bilateral aldosteronism without hypokalemia or computed tomographic findings, potentially representing the false-positive PA diagnosis rate with omission of confirmatory tests in this population. In a hypertension referral unit enriched in high-probability PA cases and where high AVS success is achieved, omission of a PA confirmatory test yields a high rate of surgical diagnosis with few potential false-positive diagnoses., (©2014 Wiley Periodicals, Inc.)

We hypothesized aldosteronoma responsiveness to cosyntropin may be a characterizing feature that could be determined in addition to standard adrenal vein sampling (AVS) data. We reviewed an AVS database from June 2005 to October 2011 including 65 patients with confirmed primary aldosteronism (PA) who underwent AVS and, if applicable, unilateral adrenalectomy. Patients were divided into confirmed lateralized and non-lateralized groups and subgrouped by histology. Plasma aldosterone in inferior vena cava (IVC) pre- and post-cosyntropin infusion during AVS was measured. Peak aldosterone and proportional change was compared between groups. Baseline and peak IVC aldosterone was higher in lateralized patients but incremental aldosterone rise was much greater in subjects with bilateral hyperplasia. From receiver operator characteristics (ROC) analysis, the optimized diagnostic cut point of peak IVC aldosterone of >649 pmol l(-1) would have a sensitivity of 94% for surgical disease although specificity of just 59%. A 250% increase in IVC aldosterone following cosyntropin would be specific enough to exclude 87% of surgical/lateralized disease. These diagnostic capabilities are similar to other results with non-AVS tests performed for diagnosis of lateralization. Although not specific enough to replace standard AVS interpretation, a marked IVC aldosterone increase after cosyntropin during AVS is a useful additional test to diagnose non-lateralizing forms of PA. Such a calculation requires no additional expense or tests.

Background: Up to 44% of primary hyperparathyroidism patients have elevated parathyroid hormone (ePTH) with normal calcium postparathyroidectomy (PTx). The question is whether the surgical approach affects the incidence of this phenomenon., Methods: Patients with hyperparathyroidism and presumed single-gland disease on preoperative imaging who underwent PTx between 1994 and 2008 were identified and contacted for long-term follow-up. PTx was either a focused approach (minimally invasive approach [MIP]) or a bilateral neck exploration (BNE)., Results: In total, 171 patients had PTH measured postoperatively (95 MIP and 76 BNE); 30 of 171 (17%) had ePTH with normal calcium (MIP 21 [22%] and BNE 9 [12%], P = .08). This occurred within 2 years in 48% and 67% and after 2 years in 52% and 33%, MIP vs BNE, respectively. Four patients recurred, 2 MIP and 2 BNE., Conclusions: There is a trend toward a higher incidence of ePTH in patients having undergone an MIP. The etiology of ePTH is multifactorial but may represent an early recurrence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Minimally invasive techniques are now often used to treat primary hyperparathyroidism but with uncertain conformity and some controversy. Endocrine surgery fellowships (ESFPs) have recently proliferated., Methods: The directors of the 19 ESFPs recognized by the American Association of Endocrine Surgeons were polled to identify the approaches currently taught to trainees., Results: With 100% participation, all ESFPs obtain ≥1 imaging study, and 95% use ultrasound to assess for concurrent thyroid nodules that require care. For an apparent single adenoma, all ESFPs minimize dissection, use intraoperative parathyroid hormone monitoring, and, if multiglandular disease is identified, perform 4-gland exploration. Outpatient surgery (89%) and postoperative oral calcium use (68%) are common. All programs define cure as durable normocalcemia (median, 6 months)., Conclusions: American Association of Endocrine Surgeons fellowship programs teach congruent management strategies that include focused dissection, intraoperative parathyroid hormone use, and intent to cure. These consistencies define a future standard for assessment of parathyroidectomy outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the cognitive performance of patients with carcinoid syndrome (CS) compared with population norms and cancer patients with non-neuroendocrine (non-NET) liver metastases., Background: The release of serotonin into the systemic circulation from metastatic small bowel neuroendocrine tumors (SB NET) causes CS. Many patients with CS followed in a multidisciplinary NET clinic seemed to exhibit a unique cognitive impairment. Because serotonin is known to influence a range of cognitive function, the question arouse as to whether cognitive impairment is another manifestation of CS., Methods: Patients were recruited from the multidisciplinary NET and the hepatobilary cancer clinics at the cancer center. The CS group consisted of patients with proven SB NETs metastatic to liver; the cancer comparison group consisted of patients with liver metastases from non-NET cancer. All completed a self-reported cognitive questionnaire and a battery of 6 standardized neurocognitive tests. Both groups were compared to age/sex/educational-matched norms., Results: Thirty-six patients with CS and 20 with non-NET metastases were enrolled. Patients with CS reported greater cognitive dysfunction in all cognitive domains than both norms and the comparison cancer group. On cognitive testing, patients with CS demonstrated weakness in initiation, processing speed, visual memory, cognitive efficiency, and delayed verbal recall compared with norms. Although the patients with non-NET cancer also demonstrated some cognitive dysfunction compared with norms, the patients with CS did significantly worse on delayed recall (P = 0.03) and marginally slower on speeded mental flexibility (P = 0.097) compared with patients with non-NET cancer., Conclusion: This study confirmed our clinical observation that patients with CS suffer from cognitive impairment that is different from the non-NET cancer group and population norms.