Searchable abstracts of presentations at key conferences in endocrinology

ea0007p222 | Steroids | BES2004

A model for evaluating 11beta-hydroxysteroid dehydrogenase type 1 activity in ocular and orbital tissues

Walker E , Tomlinson J , Hughes S , Wood P , Murray P , Stewart P , Rauz S

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activates cortisol (F) from cortisone (E). Our recent human studies identified 11beta-HSD1 to the non-pigmented layer (NPE) of the ocular ciliary epithelium, confirming that this enzyme is integral to the physiology of aqueous humour (AH) production vital for the maintenance of intraocular pressure (IOP). 11beta-HSD1 has also been implicated in the pathogenesis of obesity, and our previous data have defined this enzyme i...

ea0007p223 | Steroids | BES2004

11beta-hydroxysteroid dehydrogenase type 1 and the production of cerebrospinal fluid

Rauz S , Walker E , Tomlinson J , Hughes S , Wood P , Stewart P , Murray P

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain, which then drains principally into the dural sinuses. The balance between production and drainage, in part, facilitates a normal intracranial pressure. The secretion of sodium and anions by the CP, creates an osmotic gradient driving the movement of water into the ventricles. This mechanism is analogous to that found in the ocular ciliary ep...

ea0003p263 | Steroids | BES2002

Growth hormone increases fat mass in patients with simple obesity

Tomlinson J , Crabtree N , Clark P , Holder G , Shackleton C , Stewart P

Patients with obesity are relatively Growth Hormone (GH) deficient. GH has potent effects on adipocyte biology, stimulating lipolysis but also promoting pre-adipocyte proliferation. Conversely, we have shown that cortisol inhibits pre-adipocyte proliferation and enhances differentiation. Furthermore, GH, acting through IGF-1, inhibits 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which converts the inactive glucocorticoid, cortisone (E) to active cortisol (F) in ad...

ea0056p306 | Cardiovascular Endocrinology and Lipid Metabolism | ECE2018

A multi-disciplinary approach to the management of NAFLD improves both liver and metabolic health and is cost effective

Moolla Ahmad , Motohashi Kenzo , Shard Amelia , 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 type 2 diabetes (T2DM), the principal risk factor for disease progression, liver failure and cardiovascular complications. At present there are no licensed therapies and management aims to optimise metabolic risk factors through weight loss, and pharmacological interventions for diabetes and cardiovascular disease. A multidisciplinary approa...

ea0073yi3 | Young Investigator Awards | ECE2021

The american lifestyle induced obesity syndrome (ALIOS) diet induces an increase in intestinal permeability and exacerbates inflammation in female and male mice via the TLR4 signalling pathway

Anastasia Arvaniti , Nikolaou Nikolaos , Harris Shelley , Cox Roger , Corridoni Daniele , Xin Wei , Tomlinson Jeremy , Gathercole Laura

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple steatosis to non-alcoholic steatohepatitis (NASH) with risk of progression to fibrosis and eventually cirrhosis. Dysfunction of the gut-liver axis plays a role the progression to NASH. Intestinal damage and increased permeability can increase the delivery of pathogen-associated molecular patterns (PAMPs), such as LPS and intact bacteria, to the liver where they can activate the TLR4 signall...

ea0093oc22 | Oral communication 4: Pituitary and Neuroendocrinology | EYES2023

Comparative evaluation of diagnostic performance of the most commonly used screening tests for pathological hypercortisolism: A single centre analysis

Efthymiadis Agathoklis , Loo Helen , Shine Brian , Tomlinson Jeremy , Pal Aparna , Pofi Riccardo

Background: To date, there is no consensus as to the gold-standard screening test for diagnosing Cushing’s Syndrome (CS).Objectives: This study aimed to: a) compare the ability of late-night salivary cortisol (LNSC) against overnight dexamethasone suppression test (ONDT) and urinary free cortisol (UFC) as screening test for pathological hypercortisolism (PH); b) test the performance of those tests in diagnosing Cushing’s disease (CD) or mild au...

ea0094p63 | Metabolism, Obesity and Diabetes | SFEBES2023

Androgens potently regulate sterol 12α-hydroxylase (CYP8B1) expression in mouse and human liver

Potter Tom , Gangitano Elena , Visser Jenny , Gathercole Laura , Tomlinson Jeremy , Nikolaou Nikolaos

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting 6-15% of women of reproductive age. The syndrome is characterised by a variety of reproductive and metabolic features, including hyperandrogenism, chronic anovulation and hirsutism as well as insulin resistance, dyslipidaemia, and non-alcoholic fatty liver disease (NAFLD). Specifically regarding NAFLD, androgen excess is hypothesised to have a direct effect on hepatic lipid storage, thus...

ea0094p64 | Metabolism, Obesity and Diabetes | SFEBES2023

Female AKR1D1 knockout mice are protected against diet induced obesity and insulin resistance but not hepatic steatosis

Bailey Maira , Potter Tom , Larner Dean , Morgan Stuart , Lavery Gareth , Tomlinson Jeremy , Gathercole Laura

Bile acids and steroid hormones are potent regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in the liver where it catalyses a fundamental step in bile acid synthesis and inactivates steroid hormones. We have previously shown that male, but not female, AKR1D1 knockout (KO) mice on a normal chow diet are leaner than wildtype littermates but are not protected against diet induced obesity. Here we investigate the impact of a high fat diet on female...

ea0077op2.2 | Adrenal and Cardiovascular | SFEBES2021

Single-centre analysis of 900 short synacthen tests: do pre-test clinical or biochemical variables predict failure?

Dilrukshi M D S A , Beck K J , Loo H , May C , Jafar-Mohammadi B , Pofi R , Tomlinson J W , Pal A

Short synacthen test (SST) is the most widely used dynamic test of hypothalamic-pituitary-adrenal (HPA) axis function. It’s simple to conduct but requires nursing time and is relatively costly given 15-fold price increase in synacthen since 2015. We audited our SST use with the aim of reviewing clinical indications for testing and identifying useful predictors of test outcome. Baseline referral, clinical and biochemical data were retrospectively collected for individuals ...

ea0077p43 | Metabolism, Obesity and Diabetes | SFEBES2021

5β-reductase is downregulated in patients with non-alcoholic fatty liver disease and hepatocellular carcinoma and controls metabolic and proliferative phenotype through LXR-dependent mechanisms

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

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is a liver enzyme that catalyses a fundamental step in bile acid (BA) synthesis. Both BAs and BA intermediates are established as potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial regulatory role in NAFLD and HCC. Hu...