Endocrine Abstracts

The importance of measuring renin or plasma renin activity (PRA) and aldosterone in establishing mineralocorticoid deficiency is not in doubt. Once mineralocorticoid replacement therapy is initiated, guidance suggests that optimization of mineralocorticoid dose should be based upon measurements of blood pressure, renin (or PRA), and electrolytes. The aim of this study was to explore the relationship between renin and clinically important variables to determine whether measurem...

Background: Hypopituitarism is a potential complication of trans-sphenoidal adenomectomy (TSA). Recovery of pituitary function can occur, and reassessment is required to avoid unnecessary hormonal replacement. However, frequency of re-testing is variable across centres. Aim of this study was to determine recovery rates and time to recovery of hypothalamo-pituitary adrenal (HPA) and thyroid axis after TSA.Methods: We performed a single-centre, retrospecti...

The enzyme 5β-reductase (AKR1D1) controls intra-cellular steroid hormone availability through hormone clearance. Additionally, it catalyses an essential step in bile acid (BA) synthesis. Disturbances in steroid hormones and BA metabolism have potent effects on metabolic health, therefore we hypothesize that AKR1D1 may play a role in metabolic homeostasis; the role of AKR1D1 in regulating glucose homeostasis and pancreatic function remains unexplored. We generated a global...

Steroid hormones and bile acids are potent regulators of metabolic phenotype. The enzyme 5β-reductase (AKR1D1) has a crucial role in bile acid synthesis and also generates 5β-reduced dihydrosteroid metabolites, regulating intra-cellular steroid availability though the clearance of cortisol, testosterone, androstenedione, and progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid metabolism, we have hypothesised that it plays a key role in me...

Introduction: Idiopathic intracranial hypertension (IIH) occurs in young obese women (>90%) but little is known about the metabolic characteristics in these patients. We aimed to characterise IIH fat distribution, metabolic phenotype and evaluate alterations following weight loss.Methods: IIH and matched (BMI/sex) healthy obese controls were recruited. Metabolic indices (fasting lipid, glucose, insulin), anthropological measures and body composition ...

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). The severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated, but underlying mechanisms remain poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is an important source of adipose androgen generation, activating androstenedione to testosterone (T). We postulated that AKR1C3 plays a critical role linking androgen metabolism and...

Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis. The A-ring reductases (5α-reductase type 1 (5αR1) and 2 (5αR2)) generate dihydrotestosterone from testosterone, but importantly also inactivate cortisol and are highly expressed in human liver. We propose that 5αR may regulate GC exposure and therefore may modulate metabolic phenotype in human liver.Primary human hepato...

Introduction: There is growing evidence that 11β-HSD1 expression/activity increases with age in key target tissues including adipose tissue, bone, and skin, implicating local amplification of glucocorticoids in the pathophysiology of related disease. We have previously shown that 11β-HSD1KO mice are protected from both the adverse metabolic effects of excess glucocorticoids and age-associated muscle weakness. We investigated changes in global activity and skeletal mu...

2–3% of the UK population are prescribed glucocorticoid (GC) therapy and their adverse effects contribute to a significant health burden. Suppression of endogenous GC secretion is a recognized complication of therapy, but the magnitude of the problem, together with its clinical consequences have not been determined. We conducted a retrospective study across all specialties in a large secondary–tertiary care center identifying 2782 patients who underwent 3666 250 &#95...

The primary function of brown adipose tissue (BAT) is to use lipids to generate heat through uncoupling of oxidative phosphorylation in mitochondria. Glucocorticoids (GC) have a negative effect upon BAT through inhibition of uncoupling protein 1 (UCP1) expression. Similarly, it has been reported that BAT levels decline with age and have been linked to age related accumulation of body fat, leading to the idea that improving BAT function during ageing could have a beneficial rol...