Endocrine Abstracts

A recent study has reported impaired subjective health status (SHS) in 79 patients with primary adrenal insufficiency (AI) despite routine steroid replacement1. Here we have performed a survey in a large cohort of patients with primary and secondary AI. 348 patients (148 outpatients and 200 registered participants of the self-help network for adrenal and pituitary diseases) were contacted by mail. 256 (74%) agreed to participate and received a disease specific and 3...

P450 Oxidoreductase Deficiency (ORD) is a novel form of congenital adrenal hyperplasia with biochemical evidence of combined 21-hydroxylase and 17α-hydroxylase deficiency. Mutations in P450 oxidoreductase (POR), a crucial electron donor to microsomal P450 enzymes including CYP17 and CYP21, have recently been identified as the cause of disease. Clinical features in ORD include ambiguous genitalia, glucocorticoid deficiency and craniofacial malformations resembling the Antl...

Dehydroepiandrosterone (DHEA) is the crucial androgen precursor and hyperandrogenaemia is a major feature in Polycystic Ovary Syndrome (PCOS). DHEA sulfate (DHEAS) is generated from DHEA by DHEA sulfotransferase (SULT2A1) activity. The conversion of DHEAS to DHEA by steroid sulfatase has been reported to be of minor significance in human adults and only desulfated DHEA can be converted toward androgens. Therefore, SULT2A1 activity represents the rate-limiting step regulating t...

In severe sepsis circulating DHEA sulfate (DHEAS) has been shown to decrease whilst serum cortisol increases. This has led to the suggestion of an intraadrenal shift from adrenal androgen towards glucocorticoid synthesis in severe stress. Patients with sepsis are therefore assumed to be DHEA deficient and have been suggested to benefit from DHEA replacement. However, only desulfated DHEA is biologically active and DHEAS and DHEA may not freely interconvert as previously though...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been implicated in the pathogenesis of human obesity and insulin resistance through 11-oxoreductase activation of cortisol (F) from cortisone (E) stimulating adipocyte differentiation and hepatic glucose output. In its purified state however, 11beta-HSD1 is a dehydrogenase inactivating F to E. In patients with cortisone reductase deficiency we recently identified two inactivating mutations, delta29bp and R453Q, withi...

The role of oestrogens and androgens on bone metabolism has been studied extensively. However, less is known about the effects of progestins. The progesterone receptor (PR) is expressed in human osteoblasts. Progestins have been found to stimulate osteoblast proliferation, differentiation and growth factor expression (e.g. IGFBP-5) and to increase bone formation. In postmenopausal women progestins combined with oestrogen increased bone density to a greater extent than oestroge...

(This poster is based on OC38)...

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...

Background: Quality of life (QoL) has been variously reported as normal or impaired in congenital adrenal hyperplasia (CAH) adults. We found impaired QoL in UK CAH adults (Arlt et al. Journal of Clinical Endocrinology and Metabolism 2010 95 5110–5121) and now report the relationship between QoL (SF-36) and health outcomes in these patients.Methods: Cross-sectional analysis of 151 CAH adults with 21-hydroxylase defi...

Background: Zebrafish is emerging as a comprehensive model system in endocrinology. Zebrafish synthesise steroid hormones in the interrenal (counterpart of the mammalian adrenal), gonad and brain. Data on steroidogenic pathways is patchy and steroidogenic enzymes in zebrafish have not been well characterised. Human 17α-hydroxylase (hCYP17A1) facilitates two conversion steps, 17α-hydroxylase and 17,20-lyase reactions in the adrenal and gonad. Two zCyp17a (zCyp17a1; zC...