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CONTEXT No consensus exists for management of adults with congenital adrenal hyperplasia (CAH) due to a paucity of data from cohorts of meaningful size. OBJECTIVE Our objective was to establish the health status of adults with CAH. DESIGN AND SETTING We conducted a prospective cross-sectional study of adults with CAH attending specialized endocrine(More)
The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In(More)
Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal,(More)
Anti-neutrophil cytoplasmic antibody (ANCA) tests are a routine clinical assay in most UK hospitals. We examined the role of routine ANCA testing in achieving a diagnosis of systemic vasculitis in a routine clinical setting. From April 1996 to March 2000, 2734 samples from five hospital departments were tested for ANCA by indirect immunofluorescence (IIF)(More)
Central obesity is associated with type 2 diabetes mellitus, hypertension and dyslipidaemia. This cluster of risk factors is known as the metabolic syndrome, and also occurs in people with primary glucocorticoid excess (Cushing's syndrome). Exogenous glucocorticoid use also increases the risk of cardiovascular disease. Circulating glucocorticoid(More)
11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) is a therapeutic target in metabolic syndrome because it catalyses reductase regeneration of cortisol from cortisone in adipose and liver. 11βHSD1 can also catalyze the reverse dehydrogenase reaction in vitro (e.g., if cofactor is limited). We used stable isotope tracers to test the hypothesis that both(More)
BACKGROUND Adults with congenital adrenal hyperplasia (CAH) are treated with a wide variety of glucocorticoid treatment regimens. OBJECTIVE, DESIGN AND METHODS To test whether drug dose and timing of glucocorticoid treatment regimen impacts on health outcomes. This was a cross-sectional study of 196 adult CAH patients in whom treatment and health outcomes(More)
CONTEXT Dietary macronutrient composition influences cardiometabolic health independently of obesity. Both dietary fat and insulin alter glucocorticoid metabolism in rodents and, acutely, in humans. However, whether longer-term differences in dietary macronutrients affect cortisol metabolism in humans and contribute to the tissue-specific dysregulation of(More)
OBJECTIVE Regeneration of cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) within liver and adipose tissue may be of pathophysiological importance in obesity and the metabolic syndrome. single nucleotide polymorphisms (SNPs) in HSD11B1, the gene encoding 11β-HSD1, have been associated with type 2 diabetes and hypertension in population-based(More)
OBJECTIVE 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates cortisol from cortisone. 11beta-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11beta-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11beta-HSD1 from adipose tissue and(More)