Endocrine Abstracts

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...

Increased adiposity is associated with insulin resistance, type 2 diabetes and metabolic dysfunction. Altered adipokine secretion, changes in local and systemic glucocorticoid metabolism and increased inflammation have all been postulated as contributory mechanisms. We have previously described changes in subcutaneous adipose tissue (SAT) gene expression that are associated with obesity and glucose intolerance in cross-sectional studies. However, the effects of longitudinal ch...

Context: Androgen excess, obesity and hyperinsulinaemia are the cardinal features of polycystic ovarian syndrome (PCOS). While several studies have addressed the relationship between androgen excess and hyperinsulinaemia, the link between androgen excess and fat distribution remains largely undefined. Recent work has highlighted the importance of adipose tissue as an organ of androgen activation. Here, we evaluated the relationship between visceral fat and androgen excess in w...

Non-alcoholic fatty liver disease is the hepatic manifestation of the global epidemic of metabolic disease. It is tightly associated with obesity and type 2 diabetes, yet the precise mechanisms that drive its aetiology are not fully defined. Steroid hormones, including glucocorticoids and sex steroids, regulate metabolic phenotype, and in addition, bile acids have recently been identified as potent metabolic regulators. AKR1D1 (5β-reductase), is predominantly expressed in...

Background: Excess glucocorticoid (GC) exposure is associated with an adverse body composition and metabolic profile characterised by increasing fat mass, muscle atrophy, insulin resistance, fatty liver, and dyslipidaemia culminating in increased cardiovascular risk. GCs are widely prescribed with increasing age where their effects can have deleterious effects.Objectives: To investigate the impact of GC exposure on subcutaneous adipose lipid metabolism a...

Dysregulation of the enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistant states, however longitudinal changes in glucocorticoid metabolism over time have not been investigated. This study was designed to evaluate the role of pre-receptor glucocorticoid metabolism in the development of insulin resistance and obesity. 24 h urinary glucocorticoid and mineralocorticoid metabolites were measured by gas chroma...

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess. Hyperandrogenism may correlate with metabolic risk but PCOS consensus criteria currently define androgen excess on the basis of serum testosterone only. Here we studied the utility of the androgen precursor serum androstenedione in conjunction with serum testosterone as a predictor of metabolic dysfunction in PCOS.86 PCOS patients fulfilling Rott...

Non-alcoholic fatty liver disease NAFLD has been associated with androgen deficiency, yet in the majority of patients with non-alcoholic steatohepatitis NASH, androgens levels are normal. In contrast, women with polycystic ovarian syndrome PCOS, which is characterised by androgen excess, have evidence of increased liver fat. Our hypothesis is that androgen exposure to the liver may be crucial in the amount of lipid that can accumulate in hepatocytes. C3A human hepatoma cells w...

Non-alcoholic fatty liver disease (NAFLD) is characterised by intra-hepatocyte lipid accumulation. Simple steatosis, which is a reversible condition, can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. The aetiology of NAFLD is not fully understood and it is suggested that glucocorticoid reactivation through the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme may promote hepatic lipid accu...

In the pathogenesis of obesity, dysregulated tissue cortisol metabolism (controlled by 11β-HSD1), is postulated to be involved. Fifteen patients (seven mens, mean BMI 50.8±7 kg/m2) awaiting Roux En Y gastric Bypass (RYGB) surgery underwent assessment of 11β-HSD1 activity using cortisol generation profile. Corticosteroids in serum and subcutaneous adipose tissue microdialysis fluid and urinary corticosteroid metabolites were analysed by liquid and gas ...