Searchable abstracts of presentations at key conferences in endocrinology

ea0037gp.04.03 | Steroids | ECE2015

Using a morning cortisol to predict adrenal reserve and guide management

Woods Conor , Argese Nicola , Chapman Matthew , Webster Rachel , Toogood Andrew , Arlt Wiebke , Stewart Paul , Crowley Rachel , Tomlinson Jeremy

Background: The short Synacthen test (SST) is the most widely used dynamic assessment of adrenal reserve. In some situations, the SST may be difficult to perform. Random basal cortisol levels could provide an alternative screening assessment to rationalize which patients need dynamic testing. This is highly clinically relevant, given the large numbers of patients taking prescribed glucocorticoids who are at risk of iatrogenic adrenal suppression.Methods:...

ea0034p260 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

Longitudinal changes in glucocorticoid metabolism predict the development of metabolic phenotype

Crowley Rachel , Hughes Beverly , Gray Joanna , McCarthy Theresa , Hughes Susan , Shackleton Cedric , Crabtree Nicola , Nightingale Peter , Stewart Paul , Tomlinson Jeremy

Dysregulation of the enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistant states, however longitudinal changes in glucocorticoid metabolism over time have not been investigated. This study was designed to evaluate the role of pre-receptor glucocorticoid metabolism in the development of insulin resistance and obesity. 24 h urinary glucocorticoid and mineralocorticoid metabolites were measured by gas chroma...

ea0034p349 | Steroids | SFEBES2014

Hyperandrogenaemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione

O'Reilly Michael , Taylor Angela , Crabtree Nicola , Hughes Beverly , Capper Farfia , Crowley Rachel , Stewart Paul , Tomlinson Jeremy , Arlt Wiebke

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess. Hyperandrogenism may correlate with metabolic risk but PCOS consensus criteria currently define androgen excess on the basis of serum testosterone only. Here we studied the utility of the androgen precursor serum androstenedione in conjunction with serum testosterone as a predictor of metabolic dysfunction in PCOS.86 PCOS patients fulfilling Rott...

ea0034p363 | Steroids | SFEBES2014

Androgen receptor over expression drives lipid accumulation in human hepatocytes

Nikolaou Nikolaos , Nasiri Maryam , Gathercole Laura , Castro Silvia Parajes , Krone Nils , Valsamakis George , Mastorakos George , Tomlinson Jeremy

Non-alcoholic fatty liver disease NAFLD has been associated with androgen deficiency, yet in the majority of patients with non-alcoholic steatohepatitis NASH, androgens levels are normal. In contrast, women with polycystic ovarian syndrome PCOS, which is characterised by androgen excess, have evidence of increased liver fat. Our hypothesis is that androgen exposure to the liver may be crucial in the amount of lipid that can accumulate in hepatocytes. C3A human hepatoma cells w...

ea0034p371 | Steroids | SFEBES2014

Enhanced expression of hepatic inflammatory markers in 11β-hydroxysteroid dehydrogenase type 1 knockout mice fed a steatogenic diet

Larner Dean , Morgan Stuart , Gathercole Laura , Nasiri Maryam , Guest Philip , Chapman Matthew , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

Non-alcoholic fatty liver disease (NAFLD) is characterised by intra-hepatocyte lipid accumulation. Simple steatosis, which is a reversible condition, can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. The aetiology of NAFLD is not fully understood and it is suggested that glucocorticoid reactivation through the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme may promote hepatic lipid accu...

ea0031oc4.2 | Obesity, metabolism and bone | SFEBES2013

11β-HSD1 knockout mice are protected from the adverse metabolic effects of exogenous glucocorticoid excess

Morgan Stuart , Bujalska Iwona , Gathercole Laura , Hassan-Smith Zaki , Guest Phil , Abrahams Lianne , Stewart Paul , Lavery Gareth , Tomlinson Jeremy

Glucocorticoids (GC), such as prednisolone, are widely prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including insulin resistance and hepatic steatosis. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) and thus amplifies local GC action. We hypothesise that enhanced local GC regeneration of exogenously administered GCs by ...

ea0031p220 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2013

Hepatic 11β-hydroxysteroid dehydrogenase type 1 is elevated following weight loss secondary to bariatric surgery

Woods Conor , Taylor Angela , Hughes Beverly , Corrigan Michelle , Stewart Paul , Tomlinson Jeremy , Shea Donal O , Sherlock Mark

In the pathogenesis of obesity, dysregulated tissue cortisol metabolism (controlled by 11β-HSD1), is postulated to be involved. Fifteen patients (seven mens, mean BMI 50.8±7 kg/m2) awaiting Roux En Y gastric Bypass (RYGB) surgery underwent assessment of 11β-HSD1 activity using cortisol generation profile. Corticosteroids in serum and subcutaneous adipose tissue microdialysis fluid and urinary corticosteroid metabolites were analysed by liquid and gas ...

ea0028oc5.4 | Growth, tumours and pituitary | SFEBES2012

Steroid metabolomics in adrenocortical carcinoma reveals mitotane as an inducer of CYP3A4 and an inhibitor of 5alpha-reductase activity with major implications for drug metabolism and hydrocortisone replacement

Chortis Vasileios , Taylor Angela , Schneider Petra , Tomlinson Jeremy , Hughes Beverly , Smith David , Porfiri Emilio , Shackleton Cedric , Stewart Paul , Arlt Wiebke

Mitotane (o,p’DDD) is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumour. Mitotane is considered an adrenolytic substance, but no information is available regarding distinct steroidogenic effects. Here we carried out steroid metabolomics by gas chromatography/mass spectrometry in 24-hour urine samples from 106 patients with ACC and with samples coll...

ea0021p181 | Diabetes and metabolism | SFEBES2009

The influence of HIV status and antiretroviral (ARV) therapy on expression of genes related to mitochondrial metabolism in human adipose tissue (AT)

McGee Kirsty , Boothby Meg , Harte Alison , Tomlinson Jeremy , Hill Margaret , Gathercole Laura , Kumar Sudhesh , Shahmanesh Mohsen , McTernan Philip

Background and aims: The mechanisms in HIV by which mitochondrial dysfunction occurs, leading to impaired energy homeostasis and metabolic regulation, are unclear; although similarities are noted in T2DM. Therefore, we investigated the effect of HIV status and ARV therapy on several mitochondrial and nuclear encoded genes related to mitochondrial metabolism and energy homeostasis.Materials and methods: Subcutaneous AT biopsies from the ileac crest were o...

ea0015p162 | Diabetes, metabolism and cardiovascular | SFEBES2008

Adipose tissue lipid homeostasis in mice lacking hexose-6-phosphate dehydrogenase

Bujalska Iwona J , Hewitt Kylie N , Hauton David , Lavery Gareth G , Tomlinson Jeremy W , Walker Elizabeth A , Stewart Paul M

In adipose tissue, glucocorticoids (GC) are known to regulate lipogenesis and lipolysis. Hexose-6-phosphate dehydrogenase (H6PDH), a protein located in the endoplasmic reticulum (ER) provides co-factor for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thus regulating the set point of its activity and allowing for tissue specific activation of GCs. The aim of this study was to examine the effect of lack of H6PDH on adipose tissue biology using the H6P...