Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0025oc2.5 | Steroids | SFEBES2011

A novel entity of isolated adrenal insufficiency caused by partial inactivation of P450 side-chain cleavage (CYP11A1) enzyme

Parajes Silvia , Kamrath Clemens , Rose Ian , Taylor Angela , Mooij Christiaan , Dhir Vivek , Grotzinger Joachim , Arlt Wiebke , Krone Nils

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis, facilitating conversion of cholesterol to pregnenolone. Cholesterol, transported by steroidogenic acute regulatory protein (StAR) into the inner mitochondrial membrane, is converted by CYP11A1 into 22R-hydroxycholesterol. Subsequently, CYP11A1 converts 22R-hydroxycholesterol by 20alpha-hydroxylation and cleavage of the C20–C22 bond into pregnenolone. All pat...

ea0021oc3.3 | Young Endocrinologists prize session | SFEBES2009

Development of urinary steroid profiling as a high-throughput screening tool for the detection of malignancy in patients with adrenal tumours

Taylor Angela , Biehl Michael , Hughes Beverly , Stiekema Han , Schneider Petra , Smith David , Nightingale Peter , Shackleton Cedric , Stewart Paul , Arlt Wiebke

Adrenal tumors have an incidence of 2–3% in the general population and the work-up of incidentally discovered adrenal masses represents a major burden to the health system. Differentiating adrenocortical adenoma (ACA) from adrenocortical carcinoma (ACC) represents a continuous challenge, with unfavorable sensitivities and specificities provided by tumor size, imaging and even histology. Here, we aimed to develop a reliable screening tool for the detection of adrenal malig...

ea0015p331 | Steroids | SFEBES2008

Early truncation of the human CYP17A1 protein results in severe neonatal adrenal insufficiency

Ivison Hannah E , Shenoy Savitha , Arlt Felix J , Krone Nils , Shackleton Cedric HL , Taylor Norman F , Arlt Wiebke

CYP17A1 is a key enzyme of human steroidogenesis, which is unique in that it catalyses two reactions, 17-hydroxylase activity converting pregnenolone and progesterone to 17-hydroxypregnenolone (17Preg) and 17-hydroxy-progesterone, respectively, and 17,20 lyase activity, responsible for the conversion of 17Preg to dehydroepiandrosterone the crucial precursor of human sex steroid biosynthesis. 17-hydroxylase deficiency, a variant of congenital adrenal hyperplasia, results in glu...

ea0073aep332 | Diabetes, Obesity, Metabolism and Nutrition | ECE2021

Prevalence of obesity and its association with metabolic diseases in women from low-and-middle income countries (LMICs): A systematic review and meta-analysis

Rocha Thais , Melson Eka , Zamora Javier , Borja M. Fernandez-Felix , Soby Soha , Betran Ana Pilar , Arlt Wiebke , Thangaratinam Shakila

IntroductionObesity is a global health challenge, with more than 50% of the world´s obese population residing in LMICs. Although adiposity is a well-known major risk factor for noncommunicable diseases (NCDs) such as hypertension, and diabetes mellitus, the delivery of effective NCDs interventions is still a challenge to health systems. About 85% of the NCDs premature deaths occur in LMICs. Obesity is more prevalent in women than men, however the bu...

ea0075a21 | Adrenal gland | EYES2021

Impact of COVID-19 on patients with primary adrenal insufficiency: A cross-sectional study

Knowles Gregory , Warmington Emily , Shepherd Lisa , Hazlehurst Jonathan , De Bray Anne , Gleeson Helena , Arlt Wiebke , Prete Alessandro

Background: Patients with primary adrenal insufficiency (PAI) carry an increased risk of infections which can precipitate adrenal crises. They are thought to be more likely to contract COVID-19 and develop severe disease; however, little is known about the true impact of COVID-19 on these patients.Objectives: To assess the response of a large single-centre cohort of PAI patients to COVID-19, focusing on morbidity and health promotion attitudes.<p cla...

ea0077oc4.5 | Adrenal and Cardiovascular | SFEBES2021

Circulating cell-free DNA-based biomarkers as a tool for disease surveillance in adrenocortical carcinoma

Smith Gabrielle , Lippert Juliane , Altieri Barbara , Elhassan Yasir , Landwehr Laura , Prete Alessandro , Appenzeller Silke , Chortis Vasileios , Steinhauer Sonja , Asia Miriam , Sutcliffe Robert , Arlt Wiebke , Fassnacht Martin , Ronchi Cristina

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. Here we investigated the role of circulating cell-free DNA (ccfDNA) in ACC monitoring. We extracted ccfDNA from 1-4 ml EDTA-plasma using the Nonacus Cell3TMXtract or the Qiagen QIAamp MinElute kit and quantified by fluorimeter. We investigated 63 patients with ACC (25M/38F, 52±...

ea0077p114 | Reproductive Endocrinology | SFEBES2021

PCOS pearls - gathering perceptions and opinions from lived experiences of people with polycystic ovary syndrome

Lau Gar Mun , Elghobashy Mirna , Busby Maureen , Stacke Kristine , Gleeson Helena , Robinson Lynne , Arlt Wiebke , Lindenmeyer Antje , Gillett Caroline , Kempegowda Punith

Introduction: Existing educational resources for polycystic ovary syndrome (PCOS) have limited inclusion of patient perspectives. We invited people with PCOS to share their lived experiences to understand their perception and opinion on the current standard of care.Methodology: Women aged 18-60 years with PCOS were invited to complete an online survey in April and May 2021. The survey had open questions focused on people’s lived experiences with PCO...

ea0081oc13.4 | Oral Communications 13: Adrenal and Cardiovascular Endocrinology 2 | ECE2022

Classic and 11-oxygenated androgens in serum and saliva across adulthood and the menstrual cycle – a mass spectrometry-based cross-sectional study

Kempegowda Punith , Schiffer Lina , Adaway Jo , Shaheen Fozia , Ebbehoj Andreas , Singh Sumitabh , Prete Alessandro , Hawley James M , Sitch Alice J , Keevil Brian , Bancos Irina , Taylor Angela , Arlt Wiebke

Objective: Quantify classic and 11-oxygenated androgens in serum and saliva and determine variations across age, sex, body mass index (BMI), menstruation and hormonal contraception use.Methods: Morning serum samples were collected from 292 healthy volunteers (125 men, 22-95 years; 167 women, 21-91 years). Morning saliva was collected from 83 healthy volunteers (51 women, 32 men). 25 individuals (12 women, 13 men) also collected a 7-timepoint diurnal sali...