Abstract-Blacks have a high prevalence of hypertension and adrenal cortical adenomas/hyperplasia. We evaluated the hypothesis that adrenal steroids are associated with hypertension and the metabolic syndrome in blacks. Ambulatory blood pressures, anthropometric measurements, and measurements of plasma renin activity (PRA), aldosterone, fasting lipids, glucose, and insulin were obtained in 397 subjects (46% hypertensive and 50% female) after discontinuing antihypertensive and lipid-lowering medications. Hypertension was defined as average ambulatory blood pressure Ͼ130/85 mm Hg. Late-night and early morning salivary cortisol, 24-hour urine-free cortisol, and cortisone excretion were measured in a consecutive subsample of 97 subjects (40% hypertensive and 52% female). Compared with normotensive subjects, hypertensive subjects had greater waist circumference and unfavorable lipid profiles, were more insulin resistant, and had lower PRA and higher plasma aldosterone and both late-night and early morning salivary cortisol concentrations. Twenty-four-hour urine-free cortisol and cortisone did not differ. Overall, ambulatory blood pressure was positively correlated with plasma aldosterone (rϭ0.22; PϽ0.0001) and late-night salivary cortisol (rϭ0.23; Pϭ0.03) and inversely correlated with PRA (rϭϪ0.21; PϽ0.001). Plasma aldosterone correlated significantly with waist circumference, total cholesterol, triglycerides, insulin, and the insulin-resistance index. Based on Adult Treatment Panel III criteria, 17% of all of the subjects were classified as having the metabolic syndrome. Plasma aldosterone levels, but not PRA, were elevated in subjects with the metabolic syndrome (Pϭ0.0002). The association of aldosterone with blood pressure, waist circumference, and insulin resistance suggests that aldosterone may contribute to obesity-related hypertension in blacks. In addition, we speculate that relatively high aldosterone and low PRA in these hypertensive individuals may reflect a mild variant of primary aldosteronism. Key Words: aldosterone Ⅲ cortisol Ⅲ hypertension Ⅲ metabolic syndrome Ⅲ insulin resistance Ⅲ plasma renin activity T he prevalence of hypertension in African-Americans is among the highest in the world. In the United States, compared with whites, hypertension is 50% more frequent in blacks. 1,2 Blacks develop hypertension at a young age and have higher rates of hypertension-related deaths and cardiovascular complications including stroke, heart disease, and end-stage renal disease. 2 In both black and white populations, hypertension is frequently associated with centripetal obesity, insulin resistance, and dyslipidemia. [3][4][5] This constellation of risk factors has been termed the metabolic syndrome and is associated with increased cardiovascular disease morbidity and mortality. 6,7 Based on an earlier study of the records of 35 000 consecutive autopsies, an increased prevalence of adrenal cortical adenomas and hyperplasia has been observed in association with essential hypertension, particularly in younger and ...
Objective: Cushing's syndrome (CS) is difficult to diagnose due to its nonspecific presentation. Diagnostic tests like 24-h urine free cortisol (UFC) and the overnight 1 mg dexamethasone suppression test (DST) lack sufficient sensitivity and specificity. Measurement of nocturnal salivary cortisol (NSC) is an accurate and reproducible test with a high sensitivity for CS. However, its performance in mild CS has not been reported. We present 11 cases of CS with normal or mildly elevated UFC in whom NSC was helpful in making a diagnosis. Design and methods: All patients had at least one collection of 24-h UFC and NSC and eight had an overnight 1 mg DST. The number of NSC measurements per patient was determined by the clinical index of suspicion and the results of initial testing. Imaging studies included magnetic resonance imaging (MRI) of pituitary or computer tomography scan of abdomen. Results: Only four out of eleven patients had elevations in UFC and none were O2 times the upper limit of normal. Seven out of eight had an abnormal DST. All patients had some elevated NSCs (14-100%). Out of eleven patients, six had an abnormality in the pituitary gland found by MRI and two out of eleven had adrenal masses. The remaining three had normal pituitary MRI but had inferior petrosal sinus (IPS) sampling indicating Cushing's disease. All patients had appropriate surgery, and histopathology of all except one was suggestive of either a cortisol-producing adrenal adenoma or an ACTH-secreting pituitary adenoma. Conclusion: Neither a normal UFC nor a normal NSC excludes mild CS. Multiple samples (urine/saliva) and DST are needed to make the diagnosis of mild CS.European Journal of Endocrinology 157 725-731
Sitosterolaemia is an extremely rare autosomal recessive disease, the key feature of which is the impairment of pathways that normally prevent absorption and retention of non-cholesterol sterols, for example plant sterols and shellfish sterols. The clinical manifestations are akin to familial hypercholesterolaemia (such as presence of tendon xanthomas and premature atherosclerosis), but with "normal to moderately elevated" cholesterol levels. The gene(s) causing sitosterolaemia was mapped to the STSL locus on human chromosome 2p21, and mutations in either of the two genes that comprise this locus, ABCG5 or ABCG8, cause this disease. Exact prevalence is unknown, but there are estimated to be 80-100 cases around the world. This rare disease has shed light into the molecular mechanisms that control sterol trafficking in the enterocyte and hepatocyte; ABCG5 and ABCG8 heterodimerise to form a sterol efflux transporter in the liver and intestine. In this review the pathophysiology, clinical manifestations and approach to clinical and laboratory diagnosis of this disease are described.
Higher ADPN and lower WHRs (higher peripheral adiposity) are associated with better metabolic health in both nonobese and obese white individuals. These results suggest that ADPN and peripheral adiposity play a key role in determining the metabolic health independent of body mass index.
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