Endocrine Abstracts

We present the case of a 76 year old woman who was admitted to our hospital with severe Cushings syndrome, in association with hair loss and hypokalaemia. Plasma cortisol levels were elevated, and did not suppress with high dose dexamethasone. ACTH levels were detectable throughout the HDDST. MRI pituitary and CT adrenals were normal, but CT of chest revealed an area of nodularity in the right lung. With no specific treatment her symptoms settled, and her biochemistry returned...

There is a significant body of research that demonstrates an association between central (visceral) obesity, insulin resistance, endothelial dysfunction and accelerated atherosclerosis, but the molecular mechanisms underlying this link are incompletely understood. In cultured human aortic endothelial cell (HAEC) models, insulin stimulates an intracellular signalling cascade resulting in activating phosphorylation of Insulin Receptor Substrate-1, Protein kinase B (PKB/Akt) and ...

In population studies, premature cardiovascular disease is associated with cortisol dysregulation. Recently, recurrent hypoglycaemia in individuals with type 1 diabetes (T1D) was reported to be associated with increase carotid intima–media thickness. Hypoglycaemia is a potent activator of the hypothalamo-pituitary–adrenal axis (HPA axis) with eventual release of cortisol. We hypothesized that individuals with T1D who experience recurrent hypoglycaemia might demonstra...

Primary aldosteronism (PA) accounts for up to 15% of cases of hypertension, and associates with increased cardiovascular morbidity. Specific treatment options include mineralocorticoid antagonists or adrenalectomy; the latter offers cure although reported rates vary between 20–60%. The role of adrenal vein sampling (AVS) in diagnosing PA remains controversial. By reviewing casenotes of PA patients treated surgically and comparing with matched medically managed PA patients...

Aldosterone synthesis is heritable; a single nucleotide polymorphism (SNP) in the promoter of the aldosterone synthase gene (position −344, rs1799998) has been associated with an increased plasma aldosterone levels and hypertension. However, deletion of this site has no effect on gene transcription in vitro and therefore the mechanism that links genotype with phenotype is unclear.We identified a polymorphism at position −1651 T/C (rs13...

The aldosterone synthase gene encodes the final step in the production of aldosterone. The aldoststerone synthase gene is polymorphic and variants within the gene and the regulatory region have been associated with hypertension and a phenotype of relatively higher level of aldosterone and its metabolites. However to date; none of the polymorphisms in the regulatory region of CYP11B2 have been shown to alter transcription. Seven novel polymorphisms in the promoter region of CYP...

ACRD presents with clinical features of hyperandrogenism in females similar to those of PCOS (acne, hirsutism, oligomenorrhea, infertility), and precocious puberty in males. Obesity also occurs in some cases. Increased cortisol clearance leads to an increased hypothalamic-pituitary-adrenal axis drive resulting in elevated serum androgen levels and a decreased urinary cortisol metabolite: cortisone metabolite ratio below 0.5 (normal adult range 0.7–1.3). These observations...

Introduction: Measurement of microRNA (miRNA) in aldosterone-producing adenoma (APA) tissue from primary aldosteronism (PA) patients show levels of the miR24-1 cluster miRNAs (i.e. miRNAs 24-1, 27b and 23b) are significantly reduced relative to normal adrenal tissue. Our previous studies also show that miRNA-24 directly targets CYP11B2 (aldosterone synthase) gene expression. Circulating miRNAs released into the bloodstream may be diagnostic biomarkers or signalling mo...

The CYP11B1 and CYP11B2 genes encode the enzymes responsible, respectively, for the terminal stages of cortisol and aldosterone biosynthesis, and have been implicated in the development of essential hypertension. Previously, we investigated the role of microRNAs in the regulation of these genes and showed in vitro that levels of the adrenally-expressed microRNA-24 (miR-24) inversely correlate with those of CYP11B1 and CYP11B2 mRNA, ...

The final reaction for cortisol production in the adrenal gland is catalysed by the 11β-hydroxylase enzyme, encoded by the CYP11B1 gene. Variants in this gene have been associated with alterations in cortisol levels, which increase blood pressure. This gene is traditionally thought to consist of 9 exons. However, recent evidence has predicted the existence of at least one alternatively spliced form.The presence of novel CYP11B1 mRN...