Endocrine Abstracts

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...

The PROactive study recently demonstrated that pioglitazone, a thiazolidinedione class drug, reduces macrovascular morbidity and mortality in patients with type 2 diabetes. This class of drug has been reported to exert PPAR gamma receptor dependent as well as receptor independent effects, possibly via AMP kinase activation (AMPK) but the precise mode of action resulting in improved cardiovascular outcome remains uncertain.We studied the effects of rosigl...

The fusion of insulin-stimulated GLUT4-containing vesicles (GSV) with the plasma membrane (PM) of adipose or skeletal muscle cells is governed by regulated exocytosis. In all such membrane fusion events cognate t- and v-SNAREs interact in an ordered way to allow vesicles to first dock with, and then fuse with the plasmalemma. In neurons, the best-studied example of this well conserved process, the protein species responsible for directing the final (rate-limiting) fusion step ...

Hypopituitary patients on conventional hormone replacement, excluding GH have a reduced quality of life (QoL) and an increased risk of cardiovascular mortality. NICE guidelines on criteria for initiation and maintenance of therapy rely on QoL score defined by the Adult GHD assessment (AGHDA) questionnaire. However, it is uncertain how this score is related to other biological effects such as vascular risk.Methods: Sixteen hypopituitary patients were recr...

Thiazolidinediones and biguanides improve insulin resistance and are used in the management of type 2 diabetes. Use of biguanides is associated with a reduction in vascular complications in patients with diabetes. Pre-clinical studies with thiazolidinediones suggest improvements in vascular function and long-term clinical trials in type 2 diabetes are in progress. These effects are proposed to be mediated through inhibition of complex 1 in the mitochondrial respiratory chain a...

Hypopituitary patients receiving conventional hormonal therapy, excluding Growth Hormone, have an increased risk of vascular mortality. Significant endothelial dysfunction with impaired aortic distensibility has been demonstrated in these patients with some improvement in arterial stiffness after GH therapy. Inflammation is central in the pathophysiology of atherosclerosis and C-reactive protein is a validated marker for predicting cardiovascular risk.Fo...