Endocrine Abstracts

Glucocorticoids (GC) are commonly prescribed and their use is associated with adverse metabolic side effects. 5a-reductase (5aR) inhibitors are also frequently prescribed mainly for their ability to inhibit the conversion of testosterone to dihydrotestosterone. However, they also have a role to inactivate and clear GCs. We hypothesised that 5aR inhibitors have the potential to exacerbate the adverse metabolic effects of GCs. We conducted a prospective, randomised, study in 19 ...

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is tightly associated with insulin resistance and type 2 diabetes (T2DM), both risk factors for disease progression, liver failure and cardiovascular complications. A multidisciplinary approach involving hepatologists and diabetologists working alongside allied health professionals is thus advocated for the management of NAFLD. Interv...

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Glucocorticoid (GC) excess drives obesity, insulin resistance and type 2 diabetes. Obstructive sleep apnoea (OSA) is a prevalent condition associated with both activation of the hypothalamic-pituitary-adrenal (HPA) axis and an adverse metabolic phenotype. However, a causal link between these two features has not been established. We designed a novel human model of intermittent hypoxia (IH) aimed at replicating the systemic insulin resistance associ...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver 5β-reductase (AKR1D1) catalyses a fundamental step in bile acid (BA) synthesis. BAs and BA intermediates are potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Liver biopsies and serum samples were obtained from healt...

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 ...

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...