Background-Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension there are no standard criteria to classify surgical outcomes.

BACKGROUND. Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess.METHODS. We performed mass spectrometry–based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess. We also analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing adenoma, employing immunohistochemistry with digital image analysis.RESULTS. Primary aldosteronism patients had significantly increased cortisol and total glucocorticoid metabolite excretion (all P < 0.001), only exceeded by glucocorticoid output in patients with clinically overt adrenal Cushing syndrome. Several surrogate parameters of metabolic risk correlated significantly with glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression was significantly associated with the corresponding in vivo glucocorticoid excretion. Unilateral adrenalectomy resolved both mineralocorticoid and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found in 13 (29%) of 45 consecutively tested patients.CONCLUSION. Our data indicate that glucocorticoid cosecretion is frequently found in primary aldosteronism and contributes to associated metabolic risk. Mineralocorticoid receptor antagonist therapy alone may not be sufficient to counteract adverse metabolic risk in medically treated patients with primary aldosteronism.FUNDING. Medical Research Council UK, Wellcome Trust, European Commission.

Abstract-Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT

Background SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin–angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. Methods ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUC SOFA ), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov , NCT04353596 . Findings Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66–80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00–2·00) vs 1·00 (0·00–3·00); p=0·12). Discontinuation was associated with a significantly lower AUC SOFA (0·00 [0·00–9·25] vs 3·50 [0·00–23·50]; p=0·040), mean SOFA score (0·00 [0·00–0·31] vs 0·12 [0·00–0·78]; p=0·040), and 30-day SOFA score (0·00 [10–90th percentile, 0·00–1·20] vs 0·00 [0·00–24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. Interpretation Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the avail...

Aldosterone excess has a direct negative effect on β-cell function in patients with PA. After adrenalectomy, glucose-induced first-phase insulin secretion improves significantly in the patients.

Context Primary aldosteronism (PA) comprises unilateral (lateralized, LPA) and bilateral disease (BPA). The identification of LPA is important to recommend potentially curative adrenalectomy. Adrenal venous sampling (AVS) is considered the gold standard for PA subtyping, but the procedure is available in few referral centers. Objective To develop prediction models for subtype diagnosis of PA using patient clinical and biochemical characteristics. Design, Patients and Setting Patients referred to a tertiary hypertension unit. Diagnostic algorithms were built and tested in a training (N=150) and in an internal validation cohort (N=65), respectively. The models were validated in an external independent cohort (N=118). Main outcome measure Regression analyses and supervised machine learning algorithms were used to develop and validate two diagnostic models and a 20-point score to classify patients with PA according to subtype diagnosis. Results Six parameters were associated with a diagnosis of LPA (aldosterone at screening and after confirmatory testing, lowest potassium value, presence/absence of nodules, nodule diameter, and computed tomography results) and were included in the diagnostic models. Machine learning algorithms displayed high accuracy at training and internal validation (79.1% to 93%), whereas a 20-point score reached an AUC of 0.896, and a sensitivity/specificity of 91.7/79.3%. An integrated flow-chart correctly addressed 96.3% of patients to surgery and would have avoided AVS in 43.7% of patients. The external validation on an independent cohort confirmed a similar diagnostic performance. Conclusions Diagnostic modelling techniques can be used for subtype diagnosis and guide surgical decision in patients with PA in centers where AVS is unavailable.

CONTEXT Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and metabolic risks. Recent studies report glucocorticoid co-secretion as a relevant phenotype of PA, which could contribute to associated risks, including type 2 diabetes mellitus (T2DM). The relationship between autonomous cortisol secretion (ACS) and glucose metabolism in PA has not been investigated. OBJECTIVE To evaluate the prevalence of impaired glucose homeostasis in PA patients according to cortisol co-secretion. METHODS We performed oral-glucose-tolerance-tests (OGTT) and complete testing for hypercortisolism (1mg-dexamethasone-suppression-test (DST), late-night-salivary-cortisol (LNC), 24hour-urinary-free-cortisol (UFC)) in 161 newly diagnosed PA patients of the German Conn Registry. 76 of 161 patients were reevaluated at follow-up. We compared our results to a population-based sample from the KORA-F4 study matched to the PA participants (3:1) by sex, age, and BMI. RESULTS At the time of diagnosis, 125 patients (77.6%) had a pathological response in at least one of the Cushing screening tests; T2DM was diagnosed in 6.4% of these 125 cases. Patients with pathological DST exhibited significantly higher 2h plasma glucose in OGTT and were significantly more often diagnosed with T2DM than patients with normal DST (20% vs. 0.8%, p<0.0001) and matched controls from the KORA study (20.6% vs. 5.9%.; p=0.022). PA patients without ACS tended to have higher homeostatic-model-assessmentof-insulin-resistance (HOMA-IR) than KORA control subjects (p=0.05). CONCLUSION ACS appears frequently in PA patients and is associated with impaired glucose metabolism, which could increase the risk of T2DM. PA itself seems to enhance insulin resistance.

Diagnostic efficiency is an important outcome variable in clinical reasoning research as it corresponds to workplace challenges. Scaffolding for case representations significantly improved the diagnostic efficiency of fourth and fifth-year medical students, most likely because of a more targeted screening of the available information.