Endocrine Abstracts

Steroid hormones and BAs are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in the liver where it inactivates steroid hormones and catalyses a fundamental step in bile acid (BA) synthesis. We have hypothesised that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis. Genetic manipulation of AKR1D1 was performed in human liver HepG2 and Huh7 cells. Expression changes were confirmed by qPCR and western blotting, ...

Background: Hypopituitarism can occur post trans-sphenoidal adenomectomy(TSA). Accurate prediction of HPA axis recovery would inform hydrocortisone replacement strategies but there are limited studies on this. In our centre, HPA axis is assessed with pre-operative short synacthen test (SST), day-8 post TSA 9am cortisol and 6-week post-TSA SST. Patients are commenced on hydrocortisone post TSA until 6 weeks review.Methods: We performed a single-centre, lo...

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the commonest cause of liver cirrhosis and leading indication for liver transplant worldwide. It is tightly associated with obesity and type 2 diabetes, yet the precise mechanisms that drive its aetiology are not fully defined. Dysregulation of both glucocorticoid and androgen metabolism has been implicated in its pathogenesis. The availability of these hormones to bind and activate their receptors is mainly regulat...

Glucocorticoids (GC) are commonly prescribed, but their use is associated with significant adverse metabolic and bone effects. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active GC within tissues, tightly controlling the availability of GC to bind and activate the GC receptor; Our preclinical data have shown that 11β-HSD1 knock out mice resist the adverse effects of exogenous GC excess. We have now conducted a randomized, double-blind, placebo...

Granulomatosis with Polyangitis (GPA) typically affects the lungs, kidneys and ENT system. Pituitary involvement is extremely rare, affecting less than 1% of all cases. The most common pituitary manifestations are secondary hypogonadism and Diabetes Insipidus (DI).Corticosteroids and immunosuppressive agents represent mainstay of medical management. Treatment needs to be initiated promptly and individualised according to clinical response.Case 1: A 54-ye...

Background: Acid-labile subunit (ALS) deficiency inhibits ternary complex formation leading to primary IGF1 deficiency and short stature. Potential metabolic consequences such as diabetes and low bone mass are not well studied.Objective: This study measured insulin sensitivity, lipid profile, bone density and structure in members of 4 affected families and explore possible gene-dose effects.Methods: Four patients (7–21 years) ...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The role of glucocorticoids (GC) in its pathogenesis, is highlighted in patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although circulating cortisol levels are normal in patients with NAFLD, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11&#94...

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing’s syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is predominantly expressed in liver and adipose tissue, regenerates active cortisol from inactive cortisone. Increased 11beta-HSD1 may cause tissue-specific Cushing syndrome with central obesity and impa...

Orbital fat (OF) represents a highly specialised adipose tissue depot that occupies a confined space behind the eyeball known as the orbit. OF fills most of the orbital cavity providing support to the delicate structures that link the eye to the brain, and protects against sight-threatening mechanical and inflammatory trauma. Subcutaneous (SC) and omental (OM) adipose tissues are highly active endocrine organs, regulated in part by glucocorticoids (GCs). The pre-receptor regul...