Searchable abstracts of presentations at key conferences in endocrinology

ea0041gp184 | Reproduction & Endocrine Disruption | ECE2016

Impaired DHEA sulfation defines androgen excess in women with polycystic ovarian syndrome (PCOS)

Kempegowda Punith , O'Reilly Michael W , Hassan-Smith Zaki , Storbeck Karl-Heinz , Taylor Angela E , Arlt Wiebke

Context: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of classic androgen synthesis. Recent work has highlighted that impaired DHEA sulfation results in enhanced androgen production. Here, we evaluated the relationship between DHEA and DHEAS and androgen excess and metabolic phenotype in PCOS.Patients and methods: We compared 65 women with PCOS to 35 healthy women matched for age and body mass index (BMI). All subject...

ea0059oc5.1 | Adrenal | SFEBES2018

Timed urinary steroid profiling of patients with different degrees of cortisol excess: a proposal for a new test for the diagnosis of Cushing’s syndrome

Prete Alessandro , Taylor Angela E , Schiffer Lina , Nestola Manuela , Pignata Luisa , Corsello Salvatore M , Arlt Wiebke

Background: Cushing’s syndrome (CS) is caused by endogenous cortisol excess and is associated with significant morbidity. Twenty-four-hour urinary cortisol is one of the most useful tools to diagnose CS although it has limitations, especially in “mild” and “subclinical” forms of cortisol excess. We hypothesized that given the diurnal rhythm of physiological cortisol secretion, night-time urinary glucocorticoid excretion should be lower than day-time ex...

ea0038oc1.3 | Early Career Oral Communications | SFEBES2015

RNA-sequencing of mouse adrenals reveals the pathways perturbed by loss of nicotinamide nucleotide transhydrogenase

Meimaridou Eirini , Goldsworthy Michelle , Chortis Vasileios , Foster Paul , Arlt Wiebke , Cox Roger , Metherell Lou

Nicotinamide nucleotide transhydrogenase (NNT) is a highly conserved inner mitochondrial membrane protein, which supplies high concentrations of NADPH for detoxification of reactive oxygen species (ROS) by glutathione and thioredoxin pathways. In humans, loss-of-function mutations in NNT cause familial glucocorticoid deficiency, a potentially fatal, adrenal specific disorder characterized by increased levels of ACTH and low levels of cortisol. Nnt−...

ea0038p145 | Neoplasia, cancer and late effects | SFEBES2015

Nicotinamide nucleotide transhydrogenase (NNT) as a novel molecular target in adrenocortical carcinoma – impact of NNT knockdown on adrenocortical cell proliferation, redox balance and steroidogenesis

Chortis Vasileios , Taylor Angela , Doig Craig , Meimaridou Eirini , Metherell Lou , Arlt Wiebke , Foster Paul

Nicotinamide nucleotide transhydrogenase (NNT) is a NADPH-generating mitochondrial proton pump with a central role in mitochondrial antioxidant pathways. Recent studies revealed inactivating NNT mutations in patients with familial glucocorticoid deficiency, indicating a selective susceptibility of the adrenal cortex to NNT deficiency and oxidative stress. Here we explored the potential value of NNT as a therapeutic target in adrenocortical cancer. We delineated the distinct ef...

ea0038p228 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2015

Characterising fat distribution and response to weight loss in idiopathic intracranial hypertension

Ali Fizzah , O'Reilly Michael , Botfield Hannah , Markey Keira , Tomlinson Jeremy , Arlt Wiebke , Sinclair Alexandra

Introduction: Idiopathic intracranial hypertension (IIH) occurs in young obese women (>90%) but little is known about the metabolic characteristics in these patients. We aimed to characterise IIH fat distribution, metabolic phenotype and evaluate alterations following weight loss.Methods: IIH and matched (BMI/sex) healthy obese controls were recruited. Metabolic indices (fasting lipid, glucose, insulin), anthropological measures and body composition ...

ea0037oc5.4 | Steroids, developmental and paediatric endocrinology | ECE2015

Adipose tissue-specific androgen generation fuels an adverse metabolic phenotype in patients with polycystic ovary syndrome

O'Reilly Michael , Kempegowda Punith , Gathercole Laura , Taylor Angela , Bujalska Iwona , Tomlinson Jeremy , Arlt Wiebke

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). The severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated, but underlying mechanisms remain poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is an important source of adipose androgen generation, activating androstenedione to testosterone (T). We postulated that AKR1C3 plays a critical role linking androgen metabolism and...

ea0037oc9.3 | Adrenal 2 | ECE2015

Modelling the salivary cortisone to serum cortisol inter-relationship to predict serum cortisol under physiological conditions and after hydrocortisone

Debono Miguel , Harrison Robert , Keevil Brian , Whitaker Martin , Digweed Dena , Arlt Wiebke , Ross Richard

Introduction: Measuring serum cortisol to evaluate the normal circadian rhythm and adequacy of hydrocortisone replacement levels requires multiple readings; an expensive, cumbersome process. Conversely, salivary cortisone, a surrogate marker for free cortisol levels is non-invasive and well suited for out-patient settings. We hypothesised that salivary cortisone predicts circulating cortisol levels and can be used as an alternative marker of serum cortisol in a physiological s...

ea0037gp.30.07 | Endocrine tumours and neoplasia – General | ECE2015

Steroid metabolome analysis reveals that prostate cancer has potent 5α-reductase, 3α- and 17β-hydroxysteroid dehydrogenase activities, but lacks 17-hydroxylase/17,20-lyase

Hofland Johannes , Taylor Angela E , Turgeman Orli , O'Neil Donna M , Foster Paul A , Arlt Wiebke

Introduction: Prostate cancer (PC) is dependent on androgen receptor (AR) activation by its canonical ligands testosterone and 5α-dihydrotestosterone (DHT). Intratumoural androgens persisting after castration give rise to castration-resistant PC (CRPC). These intraprostatic androgen levels are hypothesized to result from either adrenal androgen conversion or intratumoural de novo DHT synthesis through the classic or alternative pathways. Quantifying the steroid f...

ea0037ep1145 | Endocrine tumours | ECE2015

Mitotane treatment for metastatic Leydig cell tumour

Chortis Vasileios , Johal Nicholas , Cullen Michael , Bancos Irina , Guest Peter , Porfiri Emilio , Arlt Wiebke

Introduction: Testicular leydig cell tumours (LCTs) are rare stromal tumors often associated with androgen excess. Metastatic malignant LCTs typically show resistance to radiotherapy and cytotoxic chemotherapy, calling for alternative management options. Here we describe our experience with treatment of two patients with metastatic LCTs with the adrenolytic drug Mitotane.Patients/methods: Case 1: A 51-year-old patient presented with a 6 month hi...

ea0034s5.1 | Endocrine consequences of major trauma | SFEBES2014

The immune-endocrine mechanisms of trauma-induced sarcopenia

Hampson Peter , Foster Mark , Taylor Angela , Bentley Conor , Fallowfield Joanne , Midwinter Mark , Arlt Wiebke , Lord Janet

Advances in trauma care have improved survival resulting in more severely injured individuals surviving to enter the trauma care pathway. A significant threat to recovery is now the dysregulated immune response to injury. The hyperinflammatory response of the innate immune system (SIRS), combined with immunoparesis, leads to complications such as multi-organ failure and sepsis. Moreover, recovery from trauma is significantly affected by age, which may be due to changes in the ...