Searchable abstracts of presentations at key conferences in endocrinology

ea0038p193 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2015

Women with idiopathic intracranial hypertension have a distinct andro-metabolic signature compared to polycystic ovary syndrome and simple obesity

O'Reilly Michael , Kempegowda Punith , Botfield Hannah , Ali Fizzah , Taylor Angela , Hughes Beverley , Tomlinson Jeremy , Arlt Wiebke , Sinclair Alex

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity.Patients and methods: We studied 25 patients with IIH (mean age 34.4±9.2 years; mean BMI 37.8±5.2 kg/m2), in comp...

ea0038p356 | Reproduction | SFEBES2015

Visceral fat drives 5α-reductase activity independent of BMI in women with polycystic ovarian syndrome

Kempegowda Punith , O'Reilly Michael W , Crabtree Nicola J , Taylor Angela E , Hughes Beverly A , Tomlinson Jeremy W , Arlt Wiebke

Context: Androgen excess, obesity and hyperinsulinaemia are the cardinal features of polycystic ovarian syndrome (PCOS). While several studies have addressed the relationship between androgen excess and hyperinsulinaemia, the link between androgen excess and fat distribution remains largely undefined. Recent work has highlighted the importance of adipose tissue as an organ of androgen activation. Here, we evaluated the relationship between visceral fat and androgen excess in w...

ea0038p411 | Steroids | SFEBES2015

The effect of adrenalectomy on cardiovascular morbidity in adrenal tumor patients with subclinical Cushing’s syndrome: systematic review and meta-analysis

Bancos Irina , Alahdab Fares , Crowley Rachel , Chortis Vasileios , Erickson Dana , Natt Neena , Terzolo Massimo , Arlt Wiebke , Murad Mohammad

Introduction: Patients with subclinical Cushing’s syndrome (SCS) present with increased cardiovascular morbidity and mortality, however, the beneficial effect of adrenalectomy on cardiovascular risk factors is uncertain.Objective: Systematic meta-analysis to determine the effect of adrenalectomy vs conservative follow-up on cardiovascular risk factors in patients with adrenal tumors and SCS.Methods: We searched 6 databases thr...

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:...

ea0034p160 | Growth and development | SFEBES2014

Relationships between final height and health outcomes in adults with congenital adrenal hyperplasia: United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE)

Han Thang , Stimson Roland , Rees Aled , Krone Nils , Willis Debbie , Conway Gerard , Arlt Wiebke , Walker Brian , Ross Richard

Background: Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development; however the relationship of childhood treatment with adult health outcomes is not established. We explored this by examining relationships between final height (FH) and cardiometabolic risk in CAH adults.Methods: Cross-sectional analysis of 65 men (80% salt wasting (SW) and 20% non-SW) and 134 women (74% SW and 26% non-SW), aged 18–69 years....

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...

ea0031p319 | Steroids | SFEBES2013

Identification of a duplicated P450 side-chain cleavage enzyme (zCyp11a2) defines initiation and maintenance of steroidogenesis in zebrafish

Parajes Silvia , Griffin Aliesha , Taylor Angela , Shackleton Cedric , Miguel-Escalada Irene , Arlt Wiebke , Mueller Ferenc , Krone Nils

Zebrafish has emerged as an important vertebrate in vivo model to study human disease. Steroidogenesis in zebrafish is not well characterised. Human CYP11A1 (hCYP11A1) catalyses the first step of steroidogenesis, the conversion of cholesterol to pregnenolone. Zebrafish Cyp11a1 (zCyp11a1) is essential during embryogenesis. Published data suggest that zCyp11a1 facilitates steroidogenesis in the interrenal (equivalent to mammalian adrenal), gonad and brain. We identified...

ea0028oc1.7 | Young Endocrinologists prize session | SFEBES2012

Progressive adrenal insufficiency and 46,XY DSD caused by two novel mutations in the cytochrome P450 side-chain cleavage (CYP11A1) gene

Parajes Silvia , Chan Angel , But Betty , Rose Ian , Taylor Angela , Griffin Aliesha , Dhir Vivek , Arlt Wiebke , Krone Nils

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individuals, with nor...

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...

ea0025oc1.6 | Young Endocrinologists prize session | SFEBES2011

Evidence for the existence and significance of an alternative pathway towards androgen synthesis during early human life

Reisch Nicole , Dhir Vivek , Berry Andrew , Taylor Angela , Krone Nils , Nogueira Edson , Shackleton Cedric , Hanley Neil , Arlt Wiebke

Congenital adrenal hyperplasia due to P450 oxidoreductase (POR) deficiency (ORD) results in disordered sex development (DSD) in individuals of both sexes. POR provides electrons to CYP17A1 thereby facilitating synthesis of the major androgen precursor dehydroepiandrosterone (DHEA). ORD disrupts this enzymatic step, resulting in deficient synthesis of 5α-dihydrotestosterone (DHT) via DHEA, readily explaining undervirilisation (46,XY DSD) in male ORD neonates. Female virili...