Endocrine Abstracts

Background: 11β-hydroxysteroid dehydrogenases (11β-HSD1&2) interconvert cortisol (F) and cortisone (E). Although 11β-HSD1 reductase activity has been measured in vivo, E production (dehydrogenase activity) has not been quantified using a Gold Standard technique, steady state tracer infusion.Aim: To develop a method to measure E production in vivo using the stable isotope tracer d2-cortisone (d2E).Me...

Background: No treatment guidelines exist for CAH adults. To address this we have undertaken a cross-sectional analysis of health status.Patients and methods: Three hundred and eighty patients from 17 tertiary centres were contacted: 203 (53%) consented (138 f, 65 m, median age 34 (range 18–69) years). One hundred and sixty-five had classic and 34 non-classic CAH. The UK prevalence is 3591 adults >18 years therefore the capture rate was 5.7%. Re...

Background: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations.Objective: To describe the clinical manifestations of subjects with SDH-B gene mutations.Design: Retrospective case series.Patients: Thirty-two subjects with SDH-B gene mutations followed-up between 1975 and 2007. Mean follow-up of 5.8 years (S.D....

Alterations in the rate of glucocorticoid(GC) metabolism induce compensatory changes in GC secretion under the control of the hypothalamic-pituitary-adrenal (HPA) axis. The principal routes of metabolic clearance of GCs are by hepatic A-ring reduction however the regulation of these enzymes is poorly understood. Recently we and others have demonstrated that bile acids act as potent inhibitors of GC metabolism by 5beta-reductase and 11beta-hydroxysteroid dehydrogenases in vi...

Previously, we have shown that 5α-tetrahydrocorticosterone (5αTHB), the reduced metabolite of corticosterone (B, the main glucocorticoid in rodents), binds to the glucocorticoid receptor, suppresses the HPA axis but has weak in vivo effects on adipose tissue and liver metabolism. Here we have compared the anti-inflammatory effects of B and 5αTHB in three in vitro and in vivo experiments. Cytokine release was measured by cytometric bead array...

BAFF, a member of the TNF family, promotes autoantibody production by increasing B cell survival and proliferation. We have previously shown that serum BAFF concentrations are increased in GD patients. In the present work, we studied the expression of BAFF and BAFF-R, by immunohistochemistry (IHC) on paraffin embedded sections of: 1. orbital adipose tissue from 22 patients (5 men, 17 women) with GO (3 of them with active GO) associated with GD or Hashimoto thyroiditis in 19 an...

Background: Mutations in succinate dehydrogense-B (SDH-B) or von Hippel Lindau (VHL) genes can result in chromaffin tumours.Objective: To compare the clinical phenotypes of subjects developing chromaffin tumours as a result of SDH-B or VHL mutations.Subjects: Thirty-one subjects with chromaffin tumours. Sixteen subjects had SDH-B gene mutations and 15 subjects had a diagnosis of VHL.<p ...

Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis in men of low birthweight may be an important link between early life events and adult metabolic syndrome. In animal models females are more sensitive to HPA axis programming by manipulations in utero, but whether gender influences susceptibility in humans is unknown.We studied 106 women aged 67-78 y, from Hertfordshire UK, in whom birthweight was recorded. None had pituitary or adrenal disease or were rec...

5alpha-Reductase 1 (5aR1) catalyses A-ring reduction of glucocorticoids and androgens. We previously demonstrated that transgenic disruption of 5aR1 predisposes male mice to fatty liver and insulin resistance when challenged with a high-fat diet. Here, we have dissected the contributions of androgens and glucocorticoids to the metabolic phenotype using 2 models of enzyme inhibition (trangenesis and pharmacology).Female 5aR1−/− mice (KO) and w...

Hepatic A-ring reduction of glucocorticoids is enhanced in obesity, perhaps contributing to compensatory activation of the hypothalamic-pituitary-adrenal axis and adrenal androgen excess. One pathway activated is the formation of tetrahydro metabolites by two sequential steps catalysed by 5beta-reductase (5bR) followed by 3alpha-hydroxysteroid dehydrogenases (3HSD). However, regulation of these enzymes is understood poorly. 5bR and 3HSD are also involved in the conversion of c...