Endocrine Abstracts

Background: There is currently no agreed consensus for the optimization and titration of mineralocorticoid (MC) therapy in patients with primary adrenal insufficiency (PAI).Objective: To explore the relationship between serum (sFC) and urine (uFC) fludrocortisone levels and biochemically and clinically important variables, and to assess their utility in guiding and titrating MC replacement.Methods: Multi-centre, observational, cros...

Background: There is currently no agreed consensus for the optimization and titration of mineralocorticoid (MC) therapy in patients with primary adrenal insufficiency (PAI).Objective: To measure serum (sFC) and urine (uFC) fludrocortisone levels and explore their relationship with biochemically and clinically important variables (including treatment compliance) in order to evaluate their usefulness as markers to guide the MC replacement titration.<p ...

A 48-year-old male presented with headache, cough and recurrent nose bleeds. Clinical examination showed saddle shape nose deformity. His past medical history included primary hypothyroidism diagnosed at the age of 10 years, was taking levothyroxine. His brother had a Rathke’s cleft cyst, surgically removed. His blood test were as follows: Sodium 125mmol/l, TSH 0.10mU/l, free T4 10.2pmol/l, freeT3 2.6pmol/l, cortisol < 28nmol/l, prolactin 240mU/l, FSH 1.8U/l, LH 0.3U/...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It is a spectrum of disease ranging from simple intracellular lipid accumulation and eventually progressing to cirrhosis and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is highly expressed in human liver and catalyzes a fundamental step in bile acid (BA) synthesis. BAs are established as potent regulators of metabolic phenotype and we have hypothesised that AKR1D1 plays...

Disruption of the gut-liver axis contributes to metabolic syndrome and the progression of non-alcoholic fatty liver disease (NAFLD). Bile acids (BAs) are potent antimicrobials that support gastrointestinal health and dysregulation of BA homeostasis in NAFLD is thought to contribute to gut dysbiosis. Furthermore, an increase in hydrophobic (cytotoxic) BA species may directly affect gut health. We have previously shown that bile acid synthesis enzyme, 5β-reductase (AKR1D1),...

Metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), are increasing in prevalence. Steroid hormones are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human liver, inactivating steroid hormones, including glucocorticoids and androgens. The human AKR1D1 gene contains 9 exons; six splice variants have been identified and three lead to functional protein isoforms (AKR1D1-001, -0...

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid synthesis. In addition, it controls intra-cellular steroid hormone availability through hormone clearance. As disturbances in steroid hormones and bile acid metabolism have potent effects on metabolic health, we hypothesize that AKR1D1 may play a role hepatic lipid accumulation. We generated global AKR1D1 knockout mice (KO) alongside wild-type controls (WT). Mice were fed either normal chow (NC) or ...

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid synthesis, but in addition, controls intra-cellular steroid hormone availability by generating 5β-reduced dihydrosteroid metabolites. As disturbances in steroid hormone and bile acid metabolism have potent effects on metabolic health and lipid homeostasis, we hypothesize that AKR1D1 may play a role hepatic lipid accumulation and contribute to the development of metabolic disease. We generated a...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and catalyzes a fundamental step in bile acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids are established regulators of metabolic phenotype. We hypothesized that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis. Genetic manipulatio...

Introduction: Glucocorticoids (GC) are prescribed to 2–3% of the population of the UK and USA. Their use is associated with a significant side effect profile that includes the development of central obesity, insulin resistance and type 2 diabetes. 5α-reductase (5αR) inhibitors (Finasteride and Dutasteride) are also commonly prescribed in the context of prostate disease, where they inhibit the conversion of testosterone to dihydrotestosterone. Additionally, they ...