Endocrine Abstracts

We present two cases of postmenopausal, gonadotrophin-dependent androgen excess.Case 1: A 59-year-old postmenopausal female presented with a 4-year history of hirsuitism and male pattern balding. Past medical history included Type II diabetes, hypertension, and polycystic ovarian syndrome. Investigations revealed androgen excess (testosterone 8.9 nmol/l [ref range<2.5], free androgen index 31.8 [ref 0-7], androstenedione 13.7 nmol/l [ref<6.8], DH...

Insulin resistance states are associated with endothelial dysfunction, but the molecular mechanisms underlying this association are incompletely understood. Impairment of insulin stimulated endothelial NO production is proposed to be a key mechanism in this process. In cultured human aortic endothelial cell (HAEC) models, insulin stimulates an intracellular signalling cascade resulting in activating phosphorylation of Insulin Receptor Substrate-1 (IRS-1), Protein kinase B (PKB...

Background: An elevated plasma aldosterone to renin ratio (ARR) is widely accepted as being important for the detection of primary hyperaldosteronism. The ability to measure renin at extremely low concentrations is the most critical factor in determining the diagnostic reliability of the ARR. We carried out this study to establish a reference interval for the ARR as part of an evaluation of a new automated platform for the simultaneous measurement of aldosterone (PAC) and dire...

Background: Recommendations for the diagnosis of phaeochromocytoma are based on individual institutional experience but have traditionally advocated concurrent measurement of urine and plasma catecholamines. However, reports of phaeochromocytoma presenting with normal catecholamines suggest that this practice is insufficiently sensitive. In phaeochromocytoma there is an increased output of metadrenaline metabolites with a disproprtionate increase in the unconjugated form and e...

BackgroundPatients with Growth Hormone Deficiency (GHD) are known to have an excess risk of vascular disease. Previous work has shown an increase in their arterial stiffness. The effect of GH on blood pressure is still unclear.Materials and Methods16 patients with GHD (6 males) and no history of existing vascular disease or hypertension, between the ages of 18 and 65 were recruited (mean 45.4 plus/minus 3.5 y...

Introduction. As for many minor metabolites of steroids, no authentic standard is commercially available for 18-OH-THA. This compound is the principal urinary metabolite of 18-hydroxycorticosterone, a putative intermediate in the synthesis of aldosterone and of diagnostic value in screening for hypermineralocorticoidism. Since de novo synthesis is time-consuming and expensive, we tested the possibility of using beta-cortol, which produces an ion at m/z 457 in common wit...

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...