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BackgroundThe 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.MethodsAmerican 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.ResultsTwelve 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, χ2= 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).ConclusionAlthough 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.

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).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.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).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.

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.

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 for12 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).

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 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 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

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.

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.

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.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.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.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.

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.

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.

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).

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 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.

Objective We previously highlighted the problem of frequent false positives in 24 hour 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 hour 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.

Objective To examine factors associated with the reported incidence of pheochromocytoma and paraganglioma across studies. Methods The annual incidence of pheochromocytoma and paraganglioma was examined according to geographic altitude and year of detection. Results Although higher altitude and later year of detection were associated with a higher incidence of disease, these variables only accounted for a small degree of the between-study differences observed. There were large amounts of residual statistical heterogeneity after meta-regression. Other factors such as variable disease detection methods, data sources, and study quality were likely more important sources of statistical heterogeneity. Conclusion Variations in the incidence of pheochromocytoma and paraganglioma between studies were only partially explained by elevation and time of detection. Other factors, such as differences in study quality and the presence of clinical heterogeneity, likely impacted estimates of incidence.

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

Objective Adrenal vein sampling (AVS) and computed tomography (CT) often show confusingly discordant lateralisation results in primary aldosteronism (PA). We tested a biochemical algorithm using AVS data to detect cortisol cosecretion as a potential explanation for discordant cases. Design Retrospective analysis from a large PA + AVS database. Patients All patients with PA and AVS, 2005-2020. Measurements An algorithm using biochemical data from paired AVS + CT images was devised from physiological first principles and informed by data from unilateral, AVS-CT concordant patients. The algorithm involved calculations based upon the expectation that low cortisol levels exist in adrenal vein effluent opposite an aldosterone-and-cortisol-producing adrenal mass and may reverse lateralisation due to inflated aldosterone/cortisol ratios. Main outcomes The algorithm was applied to cases with discordant CT-AVS lateralisation to determine whether this might be a common or explanatory finding. Clinical and biochemical characteristics of identified cases were collected via chart review and compared to CT-AVS concordant cases to detect evidence of biological plausibility for cortisol cosecretion. Results From a total of 588 AVS cases, 141 AVS + CT pairs were clear unilateral PA cases, used to develop the three-step algorithm for AVS interpretation. Applied to 88 AVS + CT discordant pairs, the algorithm suggested possible cortisol cosecretion in 40%. Case review showed that the proposed cortisol cosecretors, as identified by the algorithm, had low/suppressed adrenocorticotropic hormone levels, larger average nodule size and lower plasma aldosterone. Conclusions Pending external validation and outcome verification by surgery and tissue immunohistochemistry, cortisol cosecretion from aldosteronomas may be a common explanation for discordant CT-AVS results in PA.

Objective Exposure to high altitude may be a modifiable risk factor for pheochromocytoma and paraganglioma. The primary objective was to examine the association between the reported incidence of pheochromocytoma and paraganglioma across studies with differences in altitude. Design Meta-analysis with meta-regression. Methods The annual incidence proportion of pheochromocytoma and paraganglioma per 100,000 population was examined, accounting for differences in altitude. Meta-analysis using restricted maximum likelihood estimates with a random effects model was performed and meta-regression conducted to explore for heterogeneity. Results A total of 7 studies were identified from European, North American, and Asian countries. The pooled annual incidence proportion was 0.38 cases per 100,000 people (95% confidence interval [CI], 0.20 to 0.57 cases per 100,000 people) and this was associated with high amounts of statistical heterogeneity (P Conclusion The incidence of pheochromocytoma and paraganglioma increased with altitude. However, variations between studies were only partially explained by elevation. Other factors, such as differences in study quality and the presence of clinical heterogeneity, likely impacted estimates of incidence.

Over the last three decades, preoperative imaging for hyperparathyroidism (HPT) has drastically improved. It is crucial to recognize that preoperative localization studies should only be utilized for surgical planning in patients with the confirmed diagnosis of HPT. The success of the primary operation still relies on the experience of the surgeon and his or her ability to interpret the information obtained from preoperative imaging studies within the context of the operative findings. As such, preoperative parathyroid imaging studies serve as adjuncts for the operating surgeon, who must recognize and understand the limitations of each of these modalities when planning and performing a parathyroid operation.

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.

A bilateral neck exploration (BNE) is a fundamental skill for any surgeon involved in the treatment of parathyroid disease, and it remains the gold standard procedure for the management of hyperparathyroidism (HPT). In experienced hands, it is a safe and highly effective procedure. Furthermore, it is a cost-effective operation that can be performed anywhere in the world, without need for sophisticated preoperative imaging modalities or intra-operative surgical adjuncts. This chapter describes the morphological information and technical steps that facilitate performing this operation in a safe and efficient manner.

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.

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. 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). 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. 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: 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.

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.

Primary aldosteronism (PA) is the most common cause of remediable hypertension. Treatment is informed by establishing whether disease is unilateral (localized to one adrenal gland) or bilateral. Adrenalectomy is the guideline-recommended treatment of choice for unilateral PA. However, the currently recommended subtyping test, adrenal vein sampling (AVS), is often limited in accessibility. Thus, prediction models have been developed to diagnose unilateral PA and therefore bypass AVS. However, their generalizability remains unknown. In this retrospective study, we aimed to externally validate the performance of prediction models for unilateral PA in a large population of PA patients at a Canadian referral center who underwent AVS during 2006–2018. The presence of unilateral disease was indicated by a lateralization index of >3 on AVS. We identified 6 clinical prediction models from the literature. The discrimination and calibration of each model were systematically evaluated. For the original models, the derivation cohorts were based out of Japan, France, Italy, and England, with mean age between 46–54 years and 43–56% being male. The derivation cohorts were generally small, with 4 of the 6 studies reporting less than 50 people with unilateral PA. Common variables reported to be predictive of unilateral PA included male sex, hypokalemia, elevated aldosterone-renin ratio, and the presence of a unilateral adrenal nodule on imaging. The validation cohort included 342 PA patients who underwent successful AVS (average age, 52.1 years; 58.8% male). Among them, 186 (54.4%) demonstrated unilateral disease, and the remaining 156 (45.6%) were considered to have bilateral disease. The baseline characteristics of the validation cohort were broadly similar to those of the derivation cohorts, except for potential differences in ethnicity. When applying the models to the validation cohort, subjects were excluded if any candidate variables were missing. All 6 models demonstrated poor discrimination in the validation set (C-statistics; range, 0.59–0.72), representing a marked decrease compared to the derivation sets where they were reported (range, 0.80–0.87). Assessment of calibration by comparing observed and predicted probabilities of the unilateral subtype revealed significant miscalibration. Calibration-in-the-large for every model was >0 (range, 0.36–2.23), signifying systematic underprediction of unilateral PA. Calibration slopes were all

There is no consensus on optimal follow-up for completely resected gastroenteropancreatic neuroendocrine tumors. Published guidelines for follow-up are complex and emphasize closer surveillance in the first 3 years after resection. Neuroendocrine tumors have a different pattern and timescale of recurrence, and thus require more practical and tailored follow-up. The Commonwealth Neuroendocrine Tumour Collaboration convened an international multidisciplinary expert panel, in collaboration with the North American Neuroendocrine Tumor Society, to create patient-centered follow-up recommendations for completely resected gastroenteropancreatic neuroendocrine tumors. This panel used the RAND/UCLA (University of California, Los Angeles) Appropriateness Method to generate recommendations. A large international survey was conducted outlining current the surveillance practice of neuroendocrine tumor practitioners and shortcomings of the current guidelines. A systematic review of available data to date was supplemented by recurrence data from 2 large patient series. The resultant guidelines suggest follow-up for at least 10 years for fully resected small-bowel and pancreatic neuroendocrine tumors and also identify clinical situations in which no follow-up is required. These recommendations stratify follow-up strategies based on evidence-based prognostic factors that allow for a more individualized patient-centered approach to this complex and heterogeneous malignant neoplasm.

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.

Parathyroid surgery has evolved significantly since its inception and is associated with many pivotal discoveries that have advanced the field. From the discovery of parathyroid glands to the intraoperative measurement of parathyroid hormone this endocrinopathy continues to produce new and innovative techniques to optimize patient outcomes. This chapter describes the historical highlights that have facilitated our current practices in parathyroid surgery, the surgical approaches that have been developed including the role of intraoperative parathyroid hormone (ioPTH) measurements, and additional intraoperative adjuncts that have been developed to maximize surgical cure and minimize patient morbidity.

Insulinoma are rare neuroendocrine tumors that almost always occur in the pancreas. They produce symptoms of episodic hypoglycemia secondary to the uncontrolled release of insulin. Using contemporary non-invasive and invasive investigations, insulinoma can be localized in as many as 97% of cases preoperatively. Insulinoma that cannot be localized preoperatively can be identified at the time of surgery with the aid of intraoperative ultrasound in more than 90% of cases and successfully removed. Surgery for insulinoma is associated with significant rates of morbidity (up to 68%), but a low mortality (0–5%). When surgery is not performed, long-term symptom control of hypoglycemia is achieved in only 55–78% of cases using medical management alone. Surgery is therefore recommended for the small percentage of insulinoma that are non-localized, and should be considered preferable to observation. The strength of this recommendation by GRADE criteria is assessed as weak. Given the paucity of evidence in the literature, the overall quality of the evidence supporting this recommendation is assessed as low by GRADE criteria. The investigation and management of patients with insulinoma should be performed at specialized institutions by experienced clinicians.

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, 2015

Ideal perioperative management of pheochromocytomas/paragangliomas (pheo) is a subject of debate and can be highly variable. The purpose of this study was to identify potential predictive factors of hemodynamic instability during pheo resection. A retrospective review of pheo resections from 1992 to 2013 was undertaken. Intraoperative hemodynamics, patient demographics, tumor characteristics, and perioperative management were examined. Postoperative intensive-care admission, myocardial infarction, stroke, and 30-day mortality were reviewed. Linear regression was used to analyze factors influencing intraoperative hemodynamics. During the 20-year study period, 100 patients underwent pheo resection. Postoperative morbidity and mortality was significantly reduced (p = 0.003) in the last 10 years of practice, and there was a trend towards greater morbidity and mortality with intraoperative hemodynamic instability (p = 0.06). The preoperative dose of phenoxybenzamine and the number of laparoscopic procedures has increased in the last decade [59 mg (95 % CI 32–108) to 106 mg (95 % CI 91–124), p = 0.008, and 27 vs. 54 %, p = 0.05, respectively]. Increased preoperative phenoxybenzamine dose was a significant predictor of improved intraoperative hemodynamic stability (p = 0.01). Lack of intraoperative magnesium use resulted in greater hemodynamic instability as preoperative systolic blood pressure increased (p = 0.002). Postoperative outcomes following pheo resection have improved over the last two decades. Preoperative α-blockade plays a significant role in improving intraoperative hemodynamics and post-op outcomes. Increased doses of phenoxybenzamine and utilization of laparoscopic approaches have likely contributed to improved outcomes in the last decade. Intraoperative magnesium use may provide protection against hemodynamic instability and warrants further study.

SummaryObjective 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 adrenalaldo/cortisol to IVCaldo/cortisol ratio pre- and post cosyntropin. Hypothesis 2 was the absolute decrease in the uninvolved adrenalaldo/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

Staging is an essential component of cancer care. It is necessary to estimate prognosis, develop treatment plans, facilitate communication, and establish a bases for research efforts. Various clinicopathologic features of papillary thyroid cancer have been used to create a large number of staging systems. These systems incorporate preoperative risk factors, intraoperative findings, and postoperative results to estimate mortality and to a lesser degree recurrence. Preoperatively environmental exposures, age, gender, and genetics contribute to risk assessment in addition to physical exam and ultrasonographic findings. Intraoperative thyroid gland and lymph node assessment is important for guiding management both intraoperatively and postoperatively. Finally, postoperative response to therapy is becoming a guiding principle in the dynamic staging of patients with papillary thyroid cancer. This chapter discusses the evolution of staging systems for papillary thyroid cancer as well as patient and tumor characteristics that are evaluated at different time intervals as part of the staging process.

Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in FELESTAR, a Phase HI study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview sub study was conducted to provide insight into the patient experience in ILLESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful. Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at the end of the double-blind treatment period. Patients and interviewers were blinded to treatment. Findings: All 35 interviewed participants reported diarrhea and/or excessive BMs at baseline. Patients reported that these symptoms negatively affected emotional, social, physical, and occupational well-being. Prespecified criteria for treatment response (achieving >= 30% reduction in BM frequency for at least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and 1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described clinically meaningful reductions in BM frequency and were very satisfied with the ability of the study drug to control their carcinoidsyndrome symptoms. Overall, reports of being very satisfied were observed in 12 patients taking telotristat ethyl and 0 taking placebo. Implications: Patient interviews revealed that I ELESTAR patients, at baseline, were significantly affected by their high BM frequency. Patient reports of their clinical trial experience supported the significance of the primary end point and clinical responder analysis in TELESTAR, helping identify and understand clinically meaningful change produced by telotristat ethyl. (C) 2017 The Authors. Published by Elsevier HS Journals, Inc.

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.