Endocrine Abstracts

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...

Ion and fluid transport mechanisms within the eye are important for several key physiological processes including the maintenance of corneal transparency and the regulation of intraocular pressure (IOP). The mechanism involved in epithelial sodium transport in the eye is regulated by corticosteroids and at a pre-receptor level, by 11β-hydroxysteroid dehydrogenase (11β-HSD) activity. Recent studies localised type 1 (11β-HSD1), an oxo-reductase that activates cort...

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...

Recently, evidence has emerged that active 1,25dihydroxyvitamin D3 (1,25D3) is involved in modulating the immune response. Additionally, vitamin D3 insufficiency has been proposed as a predisposing factor for autoimmune diseases, which correlate with circulating inactive 25-hydroxyvitamin D3 (25D3). Substrate 25D3 is converted to 1,25D3 by the activating enzyme 1alpha-hydroxylase. We and others have p...

Biochemical assessment of control of CAH includes measurement of adrenal-derived androgens in blood. Some androgens like 17-hydroxyprogesterone (17OHP) have a diurnal rhythm and show a widespread of values in well controlled children. Testosterone in children (except pubertal boys) may be useful in monitoring control as it may reflect the potential for androgen action better than weaker androgens. Our salivary testosterone (SalT) assay measures free testosterone and is sensiti...

Familial expansile osteolysis is a rare autosomal dominant disorder of bone, first described in a kindred from Northern Ireland in 1988. There are histological similarities to Paget's disease but the disorder typically presents in the young.Case report: Our patient presented at 15 years of age with sensorineural hearing loss, skeletal pain, gingival hypertrophy and mobile teeth. Neither parent was similarly affected. Radiographs demonstrated tooth root r...

Neonates harbouring germline gain-of-function TSHR mutations (M453T, L629F) have been reported with transient proptosis. This resolves once euthyroidism is achieved. In contrast children expressing TSHR mutations (V597L, I486T) fail to thrive, with weight gain and height between the 0.4th and 2nd centiles. We have previously demonstrated TSHR expression in preadipocytes undergoing adipogenesis. We now investigate the consequences of constitutively active TSHR mutation expressi...

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor (MR) by inactivating cortisol. Evidence suggests impaired 11beta-HSD2 activity in some patients with hypertension but also in patients with renal disease where it may contribute to sodium retention, oedema and hypertension. To date these studies have relied upon urinary cortisol metabolite analyses as markers of renal 11beta-HSD2 activity. We have directly analysed renal 11b...

Studies in rats suggest that androgens are involved in sex-specific differences in blood pressure. In human studies there is no difference in blood pressure between boys and girls, but following puberty, men present with a higher blood pressure than women. Modulation of sodium reabsorption through the ENaC is an important component in the control of sodium balance. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohy...

The crucial role of vitamin D in mineral homeostasis is well known. However recent evidence has documented its importance for immunomodulation and inflammation. The kidney is the main source for the endocrine synthesis of the active metabolite 1,25-dihdroxyvitamin D3 (1,25D3), with expression of the key enzyme, 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-OHase). Our aim was to investigate the alteration of the vitamin D hormonal system in renal failure and assess the impact...