Endocrine Abstracts

Circulating estrogens decrease after the menopause from 60–400 to 5–30 pg/ml in postmenopausal women and in men are below 30 pg/ml. These low physiological concentrations present an analytical challenge. Analysis of steroids by tandem mass spectrometry is attractive due to its high specificity compared with immunoassays. However, estrogens do not ionise efficiently and therefore chemical modifications are necessary to achieve the sensitivity required.<p class="ab...

The glucocorticoid hormone, cortisol, regulates fuel metabolism, inflammation and stress–responses. Its circulating concentrations are tightly controlled by the hypothalamic–pituitary–adrenal axis. However, 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) generates additional cortisol in tissues, by reduction of inert cortisone. Using a tracer (9,11,12,12[2H]4-cortisol; d4-cortisol), the velocity of 11βHSD1 can be determined as t...

Inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) are being developed to prevent cortisol regeneration from cortisone in liver and adipose tissue in type 2 diabetes (T2DM). However, the target patient group is uncertain. In obesity 11β-HSD1 activity is increased in adipose tissue but decreased in liver, as judged indirectly by plasma cortisol levels after oral cortisone administration. However, in T2DM, urinary steroid ratios suggest liver 11&#946...

Introduction: It is not known if non-alcoholic fatty liver disease (NAFLD) predates type 2 diabetes. We will study the prevalence of NAFLD in women with previous gestational diabetes (GDM), a population at ≥60% risk for the development of type 2 diabetes, while glucose tolerance is non-diabetic. It is not known if hepatic fat accumulation in NAFLD is disproportionate to fat accumulation in other tissues. We aim to study the association between fat in the liver and in tis...

Background: Aldosterone levels in plasma are reported to be associated with risk of hypertension. Aldosterone secretion from the zona glomerulosa is regulated acutely by the renin/angiotensin system and plasma potassium. The role of ACTH in regulation of aldosterone secretion is disputed.Aim: We have utilised a large population study of middle aged adults to test the extent to which acute aldosterone responses to ACTH are associated with cortisol respons...

Glucocorticoids (GC) have potent anti-inflammatory effects, acting mainly through the glucocorticoid receptor (GR). However GCs have debilitating side effects and a safer alternative is required. 5α-tetrahydrocorticosterone (5αTHB, a metabolite of the natural rodent glucocorticoid corticosterone) may provide a solution: 5αTHB is anti-inflammatory in vivo, effective topically to suppress irritant dermatitis, but with fewer syst...

Glucocorticoids (GC) have potent anti-inflammatory effects, acting mainly through the glucocorticoid receptor (GR). However GCs have debilitating side effects and a safer alternative is required. 5α-tetrahydrocorticosterone (5αTHB, a metabolite of the natural rodent glucocorticoid corticosterone) may provide a solution: 5αTHB is anti-inflammatory in vivo, effective topically to suppress irritant dermatitis, but with fewer syst...

Background: Corticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and controls the circulating free cortisol pool. Proteolytic cleavage by neutrophil elastase is proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. The CORtisol NETwork (CORNET) consortium found that genetic variation at a locus spanning SERPINA1 (encoding alpha-1 antitrypsin, A1AT, the endogenous inhibitor of neutrophil elastase) and SE...

Excess action of glucocorticoid hormones is implicated in metabolic disease and cognitive decline, 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) catalysing generation of active glucocorticoid hormones in tissues. The penetration rates and tissue-specific contribution of 11βHSD1 to glucocorticoid turnover were assessed using tracer kinetics. 9,11,12,12-d4-Cortisol (d4F) was infused (1.75 mg/day, 7 days) into C57Bl6/J male mice and mice lacking 11βHSD1 (n<...

Background: Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development; however the relationship of childhood treatment with adult health outcomes is not established. We explored this by examining relationships between final height (FH) and cardiometabolic risk in CAH adults.Methods: Cross-sectional analysis of 65 men (80% salt wasting (SW) and 20% non-SW) and 134 women (74% SW and 26% non-SW), aged 18–69 years....