Apparent failed and discordant adrenal vein sampling: A potential confounding role of cortisol cosecretion?

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.

Intraoperative parathormone monitoring to predict operative success in patients with normohormonal hyperparathyroidism.

BACKGROUND: It is unclear whether parathyroidectomy guided by intraoperative parathormone (PTH) monitoring is predictive of operative success in patients with normohormonal hyperparathyroidism (nhHPT), a variant of primary hyperparathyroidism (pHPT) in which patients develop clinical manifestations similar to those of pHPT. This study examined intraoperative PTH monitoring in patients undergoing parathyroidectomy for nhHPT. METHODS: We performed a retrospective review of prospectively collected data from adult (age > 18 yr) patients who underwent parathyroidectomy for pHPT at 1 of 2 North American medical centres (in Calgary, Alberta, Canada, or Miami, Florida, United States) between 2007 and 2015. In patients with nhHPT, we used the criterion of an intraoperative decrease of more than 50% in PTH after abnormal gland excision. We defined operative success as continuous eucalcemia more than 6 months after parathyroidectomy. RESULTS: Of 333 patients, 38 (11.4%) had nhHPT, with mean preoperative calcium and PTH levels of 2.7 mmol/L and 53 pg/dL, respectively. An intraoperative decrease of more than 50% in PTH level was seen in 27 patients (71.0%) with nhHPT and 265 patients (89.8%) with classic pHPT at 5 minutes (p < 0.001); the corresponding values at 20 minutes were 35 (92.1%) and 286 (96.9%). Although 5 patients (13.2%) with nhHPT did not reach this criterion until 20 minutes, the rate of operative success was still 97.0% at long-term follow-up (mean 13 mo, range 6-67 mo). Of the 38 patients, 3 (7.9%) did not have an intraoperative decrease of more than 50% in PTH level by 20 minutes. Two of the 3 achieved operative success and remained normocalemic, and 1 developed recurrent disease at 12 months. CONCLUSION: Parathyroidectomy guided by intraoperative PTH monitoring accurately predicted operative success in patients with nhHPT. Intraoperative PTH monitoring may also help identify multiglandular disease in patients with nhHPT, using criteria similar to those in classic pHPT, with comparable operative success.

Multifocal Small Bowel Neuroendocrine Tumours.

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.

A Multi-institutional Comparison of Adrenal Venous Sampling in Patients with Primary Aldosteronism: Caution Advised if Successful Bilateral Adrenal Vein Sampling is Not Achieved.

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.

Hemodynamic Stability During Pheochromocytoma Resection: Lessons Learned Over the Last Two Decades.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group.

Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades. Pancreatic NETs are categorized as functional (F) or nonfunctional (NF) based on their ability to secrete hormones that elicit clinically relevant symptoms. Specialized diagnostic tests are required for diagnosis. Treatment options are diverse and include surgical resection, intraarterial hepatic therapy, and peptide receptor radionuclide therapy (PRRT). Systemic therapy options include targeted agents as well as chemotherapy when indicated. Diagnosis and management should occur through a collaborative team of health care practitioners well-experienced in managing pNETs. Recent advances in pNET treatment options have led to the development of the Canadian consensus document described in this report. The discussion includes the epidemiology, classification, pathology, clinical presentation and prognosis, imaging and laboratory testing, medical and surgical management, and recommended treatment algorithms for pancreatic neuroendocrine cancers.