Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism

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). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral primary aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994-2016) or AVS (526 patients, diagnosed from 1994-2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], P<0.001) and a greater proportion with absent biochemical success (29 of 235 [12%] versus 10 of 526 [2%], P<0.001). A diagnosis by CT was associated with a decreased likelihood of complete biochemical success compared with AVS (odds ratio, 0.28; 0.16-0.50; P<0.001). Clinical outcomes were not significantly different, but the absence of a postsurgical elevated aldosterone-to-renin ratio was a strong marker of complete clinical success (odds ratio, 14.81; 1.76-124.53; P=0.013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS

The 2020 Italian Society of Arterial Hypertension (SIIA) practical guidelines for the management of primary aldosteronism

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Quantitative value of aldosterone-renin ratio for detection of aldosterone-producing adenoma: The Aldosterone-Renin Ratio for Primary Aldosteronism (AQUARR) study

Background Current guidelines recommend use of the aldosterone\u2010renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false\u2010positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. Methods and Results We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone\u2010producing adenoma as reference index. We also assessed whether the post\u2010captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false\u2010positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post\u2010captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between\u2010area under the curve difference, 0.005; 95% CI, 120.031 to 0.040; P=0.7 for comparison, and 0.05; 95% CI, 120.061 to 0.064; P=0.051 for comparison, respectively). Conclusions These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure

Visceral adipose tissue: Emerging role of gluco- and mineralocorticoid hormones in the setting of cardiometabolic alterations

Abstract Several clinical and experimental lines of evidence have highlighted the detrimental effects of visceral adipose tissue excess on cardiometabolic parameters. Besides, recent findings have shown the effects of gluco-and mineralocorticoid hormones on adipose tissue and have also underscored the interplay existing between such adrenal steroids and their respective receptors in the modulation of adipose tissue biology. While the fundamental role played by glucocorticoids on adipocyte differentiation and storage was already well known, the relevance of the mineralocorticoids in the physiology of the adipose organ is of recent acquisition. The local and systemic renin-angiotensin-aldosterone system (RAAS) acting on adipose tissue seems to contribute to the development of the cardiometabolic phenotype so that its modulation can have deep impact on human health. A better understanding of the pathophysiology of the adipose organ is of crucial importance in order to identify possible therapeutic approaches that can avoid the development of such cardiovascular and metabolic sequelae

Insulin receptors and renal sodium handling in hypertensive fructose-fed rats

Background. Insulin resistance and hypertension are present in Sprague-Dawley rats fed a fructose-enriched diet. In these rats, insulin might elevate blood pressure via an antinatriuretic action. Methods. To investigate the sodium-insulin interaction in fructose-fed rats, we compared insulin sensitivity, insulin receptor binding, and insulin receptor mRNA levels in the kidney and skeletal muscle of rats that were fed standard rat chow or a fructose-enriched diet (66%) with either low (0.07%), normal (0.3%), or high (7.5%) NaCl concentrations for 3 weeks. Results. Systolic blood pressure increased in the fructose-fed rats receiving the normal and high-salt diet, but not the low-salt diet.When the rats were fed the low-salt diet, the rate of glucose infusion required to maintain euglycemia during a hyperinsulinemic clamp and insulin receptor number and mRNA levels in skeletal muscle were lower in fructose-fed than control rats. High-salt diet decreased significantly the rate of glucose disposal during the clamp and muscular insulin receptor number and mRNA levels in control, but not fructose-fed rats. During the low-salt diet, renal insulin receptor number and mRNA levels were comparable in fructose-fed and control rats and hyperinsulinemia had comparable acute antinatriuretic effects in the two groups; when the rats were maintained on the high-salt diet, the expected decrease in renal insulin receptor number and mRNA levels occurred in control but not fructose-fed rats and, consistent with this finding, the antinatriuretic response to hyperinsulinemia was blunted only in controls. An inverse relationship between dietary NaCl content and renal insulin receptor mRNA levels was observed in control but not fructose-fed rats. Conclusion. Fructose-fed rats appear to have lost the feedback mechanism that limits insulin-induced sodium retention through a down-regulation of the renal insulin receptor when the dietary NaCl content is increased. This abnormality might possibly contribute to the elevation of blood pressure in these rats

Aldosterone, mineralocorticoid receptor and the metabolic syndrome: role of the mineralocorticoid receptor antagonists

Several lines of evidence suggest a detrimental effect of aldosterone excess on the development of metabolic alterations. Glucose metabolism derangements due to aldosterone action are frequently observed not only in patients with primary aldosteronism but also in patients with obesity. A contribution to the hyperaldosteronism observed in obese subjects can be attributed, at least in part, to the action of still unidentified adipocyte-derived factor. Aldosterone, through genomic and non-genomic actions contributes to induce several abnormalities: pancreatic fibrosis, impaired beta cell function, as well as reduced skeletal muscle and adipose tissue insulin sensitivity. Oxidative stress, systemic inflammation, together with these metabolic alterations may explain the appearance of the cardiometabolic syndrome and the progression of cardiovascular and renal diseases, in the presence of inappropriate aldosterone levels. The biological actions of aldosterone are mediated by mineralocorticoid receptor (MR), although MR can be activated through an aldosterone independent fashion. Besides salt-water homeostasis, MR activation promotes inflammation, endothelial dysfunction, cardiovascular remodelling and affects adipose tissue differentiation and function. Clinical and experimental studies have shown that MR blockade is able to suppress inflammation, to improve endothelium- dependent vasorelaxation, but most interestingly, to improve pancreatic insulin release as well as insulin-mediated glucose utilization. These actions indicate MR antagonists as a useful therapeutic tool able not only to reduce cardiovascular risk and renal damage, but also to improve metabolic sequaelae

Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension

Background: Feeding a high-fructose diet induces hypertension and insulin-resistance in Sprague-Dawley rats. Methods: To investigate whether insulin receptors contribute to abnormal glucose metabolism and whether their regulation is differentially regulated in different tissues, we evaluated the glycemic and insulinemic response to an oral glucose load, insulin receptor binding, and insulin receptor messengerRNA (mRNA) levels in tissues of rats that were fed either standard rat chow or a diet containing 66% fructose for 2 weeks. Results: Blood pressure and plasma triglycerides increased significantly in the fructose-fed rats, whereas body weight, fasting plasma glucose, and plasma insulin did not differ significantly from controls. Plasma glucose and insulin responses to oral glucose were significantly greater in fructose-fed than in control rats. Insulin receptor-binding characteristics were determined by an in situ autoradiographic technique associated with computerized microdensitometry. The insulin receptor number was significantly lower in both skeletal muscle and liver of fructose- fed rats as compared to controls, whereas no difference was observed in the kidney. No significant differences were found in binding affinity. Insulin receptor mRNA levels were determined by slot-blot hybridization with a cRNA probe encoding the 5 end of the rat insulin receptor cDNA. Consistent with binding data, mRNA levels were significantly lower in skeletal muscle and liver of fructose-fed rats as compared to controls, but not in the kidney. Conclusions: Decreased number of insulin receptors occurring at the level of gene expression is present in skeletal muscle and liver of fructose-fed rats and might contribute to insulin resistance in this model

Remote management of osteoporosis in the first wave of the COVID-19 pandemic

We conducted a survey during the first pandemic wave of coronavirus disease 2019 (COVID-19) on a large group of osteoporotic patients to evaluate the general conditions of osteoporotic patients and the impact of the pandemic on the management of osteoporosis, finding high compliance to treatments and low COVID-19 lethality