Searchable abstracts of presentations at key conferences in endocrinology

ea0065cc8 | FEATURED CLINICAL CASE POSTERS | SFEBES2019

Well-differentiated grade 3 neuroendocrine tumors (G3NET) – single centre experience from the UK

Venkataraman Hema , Lithgow Kirstie , Smith Stacey , Kemp-Blake Joanne , Vickrage Suzanne , Hughes Simon , Shetty Shishir , Elshafie Mona , Gadvi Rakesh , Kharkhanis Salil , Ayuk John , Geh Ian , Shah Tahir

Introduction: The WHO classification distinguishes G3NET as a separate entity. Literature on G3NETs is limited to case-reports and small case-series. We aimed to characterise G3NETs from a large tertiary centre.Methods: Retrospective analysis from NET database: 2012–2019. All referrals are discussed at a specialist NET-MDT before entry into clinical pathway. Core NET-MDT consists of a radiologist, nuclear-medicine radiologist, histopathologist, spec...

ea0063p664 | Interdisciplinary Endocrinology 1 | ECE2019

Differential regulation of 5β-reductase (AKR1D1) expression and activity by glucocorticoids in human and rodent liver

Nikolaou Nikolaos , Morgan Stuart , Larner Dean , Sharp Anna , Raouf Zachariah , Hughes Beverly , Digweed Dena , Whitaker Martin , Ross Richard , Lavery Gareth , Arlt Wiebke , Gathercole Laura , Tomlinson Jeremy

The prevalence of metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), continues to escalate. Glucocorticoids (GCs) and bile acids (BAs) are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human and rodent liver, where it inactivates steroid hormones and catalyses a fundamental step in BA synthesis. We have previously demonstrated that AKR1D1 modulates hepatic GC availability and GC recept...

ea0049oc1.3 | Adrenal-Basic & Clinical | ECE2017

Steroid metabolomics for accurate and rapid diagnosis of inborn steroidogenic disorders

Baranowski Elizabeth , Bunte Kerstin , Shackleton Cedric H L , Taylor Angela E , Hughes Beverley A , Biehl Michael , Tino Peter , Guran Tulay , Arlt Wiebke

Background: Urinary steroid metabolite profiling is an accurate reflection of adrenal and gonadal steroid output and metabolism in peripheral target cells of steroid action. Measurement of steroid metabolite excretion by gas chromatography-–mass spectrometry (GC–MS) is considered reference standard for biochemical diagnosis of steroidogenic disorders. However, performance of GC–MS analysis and interpretation of the resulting data requires significant expertise a...

ea0044oc1.4 | Early Career Oral Communications | SFEBES2016

The urinary steroid metabolome as a non-invasive tool to stage non-alcoholic fatty liver disease

Moolla Ahmad , Amin Amin , Hughes Bev , Arlt Wiebke , Hassan-Smith Zaki , Armstrong Matt , Newsome Philip , Shah Tahir , Van Gaal Luc , Verrijken An , Francque Sven , Biehl Michael , Tomlinson Jeremy

Introduction: Dysregulation of glucocorticoid (GC) metabolism is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The only available treatment for NAFLD is weight loss and the gold standard diagnostic test is liver biopsy, which is invasive and resource intensive. NAFLD ranges from simple steatosis, to inflammation (steatohepatitis/NASH), fibrosis and cirrhosis. It may be regarded as the hepatic manifestation of the metabolic syndrome and is strongl...

ea0041gp173 | Receptors & Signalling | ECE2016

The changing ‘steroid metabolome’ across the spectrum of non-alcoholic fatty liver disease

Moolla Ahmad , Amin Amin , Hughes Bev , Arlt Wiebke , Hassan-Smith Zaki , Armstrong Matt , Newsome Philip , Shah Tahir , Van Gaal Luc , Verrijken An , Francque Sven , Biehl Michael , Tomlinson Jeremy

Introduction: Dysregulated glucocorticoid (GC) metabolism has been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). NAFLD extends from simple steatosis, to inflammation (steatohepatitis/NASH), fibrosis and consequent cirrhosis. It is often regarded as the hepatic manifestation of the metabolic syndrome and is independently associated with increased liver and cardiovascular mortality. Changes in GC metabolism have thus far been described in small num...

ea0038oc2.3 | Translational pathophysiology and therapeutics | SFEBES2015

Further advances in diagnosis of adrenal cancer: a high-throughput urinary steroid profiling method using liquid chromatography tandem mass spectrometry (LC-MS/MS)

Taylor Angela , Bancos Irina , Chortis Vasileios , Lang Katharina , O'Neil Donna , Hughes Beverly , Jenkinson Carl , Deeks Jon , Shackleton Cedric , Biehl Michael , Arlt Wiebke

Context: Differentiating adrenocortical adenoma (ACA) from adrenocortical carcinoma (ACC) represents a continuous challenge in patients with (often incidentally discovered) adrenal masses, with unfavorable sensitivities and specificities provided by tumor size, imaging and even histology. We have previously developed urine steroid metabolomics as a tool for the detection of adrenal malignancy employing gas chromatography mass spectrometry (GC-MS) for the detection of 32 distin...

ea0037oc9.2 | Adrenal 2 | ECE2015

Alternative pathway synthesis dominates androgen production in patients with congenital adrenal hyperplasia and is decreased by Chronocort® more than by conventional glucocorticoid therapy

Jones Christopher , Mallappa Ashwini , Reisch Nicole , Hughes Beverley , O'Neil Donna , Krone Nils , Whitaker Martin , Eckland David , Merke Deborah , Ross Richard , Arlt Wiebke

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...

ea0037gp.04.01 | Steroids | ECE2015

Dual 5α-reductase inhibition causes hepatic lipid accumulation in man

Hazlehurst Jonathan , Oprescu Andrei , Nikolaou Nikolaos , Grinbergs Annabel , Davies Nigel , Flintham Robert , Hughes Beverley , Taylor Angela , Yu Jinglei , Wagenmakers Anton , Tomlinson Jeremy

5α reductases 1 and 2 (SRD5A1 and SRD5A2) metabolise cortisol into inactive 5α-dihydrocortisol contributing to the regulation of cortisol availability in addition to their established role in the generation of dihydrotestosterone from testosterone. Dutasteride and finasteride are commonly prescribed to patients with benign prostatic hyperplasia but their potential metabolic effects have only recently been identified. Dutasteride inhibits both SRD5A1and SRD5A2 whilst ...

ea0037gp.04.02 | Steroids | ECE2015

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure

Sherlock Mark , Behan Lucy Ann , Hannon Mark , Alonso Aurora Aragon , Thompson Christopher , Murray Robert , Crabtree Nicola , Hughes Beverly , Arlt Wiebke , Agha Amar , Toogood Andrew , Stewart Paul M

Context: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate around the optimum glucocorticoid replacement therapy.Objective: To assess the effect of glucocorticoid replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.Design and patients: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body ...

ea0037gp.04.04 | Steroids | ECE2015

Regulation of lipogenesis in human hepatocytes by androgens, glucocorticoids, and 5α-reductase

Nikolaou Nikolaos , Nasiri Maryam , Parajes Sylvia , Krone Nils , Mastorakos George , Valsamakis George , Hughes Beverly , Taylor Angela , Bujalska Iwona , Gathercole Laura , Tomlinson Jeremy

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...