Searchable abstracts of presentations at key conferences in endocrinology

ea0050p319 | Obesity and Metabolism | SFEBES2017

The adverse metabolic phenotype associated with obstructive sleep apnoea is not driven by activation of the hypothalamo-pituitary-adrenal axis

Hazlehurst Jonathan M , Charlton Catriona , Mantripp Diana , Hodson Leanne , Tomlinson Jeremy W

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...

ea0050oc1.2 | Early Career Oral Communications | SFEBES2017

Co-administration of 5α-reductase inhibitors worsens the adverse metabolic effects of prescribed glucocorticoids

Marjot Tom , Othonos Nantia , Woods Conor , Hazlehurst Jonathan , Moolla Ahmad , Hodson Leanne , Tomlinson Jeremy

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 ...

ea0050p206 | Diabetes and Cardiovascular | SFEBES2017

The impact of a dedicated metabolic hepatology clinic for the treatment of non-alcoholic fatty liver disease

Motohashi Kenzo , Moolla Ahmad , Marjot Tom , Ainsworth Mark , Tomlinson Jeremy , Cobbold Jeremy

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...

ea0050p319 | Obesity and Metabolism | SFEBES2017

The adverse metabolic phenotype associated with obstructive sleep apnoea is not driven by activation of the hypothalamo-pituitary-adrenal axis

Hazlehurst Jonathan M , Charlton Catriona , Mantripp Diana , Hodson Leanne , Tomlinson Jeremy W

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...

ea0086oc5.2 | Metabolism, Obesity and Diabetes | SFEBES2022

7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA) is a novel AKR1D1 substrate driving metabolic dysfunction and hepatocellular cancer risk in patients with non-alcoholic fatty liver disease (NAFLD)

Nikolaou Nikolaos , Arvaniti Anastasia , Sanna Fabio , da Conceicao Ismael , Dempster Niall , Gathercole Laura , Tomlinson Jeremy

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...

ea0086op2.2 | Adrenal and Cardiovascular | SFEBES2022

Can serum and urine Fludrocortisone measurements guide mineralocorticoid replacement therapy in primary adrenal insufficiency?

Pofi Riccardo , Ilaria Bonaventura Ilaria , Duffy Joanne , Maunsell Zoe , Shine Brian , Isidori Andrea , Tomlinson Jeremy

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...

ea0090p7 | Adrenal and Cardiovascular Endocrinology | ECE2023

Treatment compliance affects the reliability of clinically and biochemically important variables used for the titration of mineralocorticoid treatment in primary adrenal insufficiency

Pofi Riccardo , Bonaventura Ilaria , Duffy Joanne , Maunsell Zoe , Shine Brian , Isidori Andrea , Tomlinson Jeremy

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 ...

ea0065oc1.4 | Metabolism and Obesity | SFEBES2019

5β-reductase (AKR1D1) is downregulated in patients with non-alcoholic fatty liver disease and protects against hepatocellular carcinoma cell proliferation in vitro

Nikolaou Nikolaos , Dempster Niall , Sgromo Bruno , Gillies Richard , Ryan John , Tomlinson Jeremy

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...

ea0065op3.2 | Metabolism and Obesity | SFEBES2019

Intestinal injury and evidence of increased gut permeability in female AKR1D1 knockout mice

Arvaniti Anastasia , Harris Shelley , Nikolaou Nikolaos , Cox Roger , Odermatt Alex Alex , Tomlinson Jeremy , Gathercole Laura

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),...