Endocrine Abstracts

The corticosteroids aldosterone and cortisol are implicated in the aetiology of hypertension. The CYP11B1 and CYP11B2 genes encode 11β-hydroxlylase and aldosterone synthase; polymorphisms across the CYP11B1/B2 locus are associated with increased aldosterone production, inefficient 11β-hydroxlation and hypertension. While polymorphisms located in the promoter region of both genes may alter transcription factor binding, other variants located in th...

Background: Vitamin D3 is generated in the skin of humans from 7-dehydrocholesterol by ultraviolet light. Vitamin D3 is hydroxylated to its metabolically active form in the liver and kidneys. The hydroxylated form of Vitamin D3, is required for both phosphate and calcium absorption in the gut and reabsorption from the kidneys. Vitamin D deficiency is associated with a low circulating calcium and phosphate.Case report: A 5...

Background: Recent studies have indicated that macroprolactinaemia accounts for up to 26% of biochemical hyperprolactinaemia depending on the assay in use. Delayed metabolic clearance of macroprolactin together with detection by most automated prolactin immunoassay systems leads to pseudo-hyperprolactinemia in patients harbouring this form of complexed prolactin.We here describe the use of serial macroprolactin measurement to assist in the management of ...

Background: Virilising congenital adrenal hyperplasia (CAH) is the most common cause of genital ambiguity, and 90–95% of CAH cases are caused by 21-hydroxylase deficiency. Associated inefficient cortisol synthesis results in increased CRH and ACTH levels, leading to production of excess sex hormone precursors. These are further metabolized to active androgens and to a lesser extent oestrogens. We recently reported that one of these androgens, DHEA-S or its metabolites sig...

Previous studies investigating steroidogenic enzymes in the brain have often focused on only a few genes at a time, using animal models or pooled human RNA to investigate their expression. For this study, we obtained RNA from individual archived human brain tissue samples in order to analyse the transcription of twelve genes involved with steroid biosynthesis and metabolism within the cerebellum and hippocampus.We developed realtime RT-PCR assays for twe...

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...

Aldosterone is key in the development of hypertension. We have shown that a SNP (−344T) in the 5’ regulatory region (UTR) of the gene encoding aldosterone synthase (CYP11B2) was associated with aldosterone excess and high blood pressure. However, the most robust phenotype is altered adrenal 11-hydroxylation efficiency (deoxycortisol to cortisol); a step carried out by 11β-hydroxylase, encoded by the adjacent gene, CYP11B1. We proposed that the effects of CYP11B...

In addition to the HLA gene region, two further genes involved in the inhibition of T cell signalling, CTLA-4 and PTPN22, have been consistently associated with autoimmune disease (AID), highlighting the important role played by molecules in this pathway in AID susceptibility. The Programmed Cell Death 1 gene (PDCD1) on chromosome 2q37.3 encodes PD-1 which is involved in providing a negative signal to activated T cells. Large case-control studies have show...

A 67 year old female presented with hypertension, oedema and cough. A CT scan of her abdomen showed an enlarged left adrenal gland. Urinary free cortisols were grossly elevated and low dose dexamethasone suppression testing confirmed Cushing’s Syndrome. 24 hour catecholamines were also elevated consistent with a diagnosis of phaeochromocytoma. ACTH levels were high (690 pg/ml) but pituitary MRI was normal. She was commenced on alpha and beta blockade in preparation for su...

(This poster is based on OC19)...