Searchable abstracts of presentations at key conferences in endocrinology

ea0027p30 | (1) | BSPED2011

Phenotypic variability of 17α-hydroxylase (CYP17A1) deficiency

Idkowiak Jan , Parajes-Castro Silvia , Shenoy Savitha , Dhir Vivek , Arun Chankramath , Arlt Felix , Malunowicz Ewa , Taylor Norman , Shackleton Cedric , T'sjoen Guy , Cheetham Tim , Arlt Wiebke , Krone Nils

The steroid 17α-hydroxylase enzyme CYP17A1 exerts two distinct activities that catalyze conversion reactions at key branch points in steroidogenesis. CYP17A1 17α-hydroxylase activity is the key step in cortisol synthesis whereas CYP17A1 17, 20 lyase activity generates sex steroid precursors. Inactivating CYP17A1 mutations result in CYP17A1 deficiency (17OHD), a rare form of congenital adrenal hyperplasia that classically presents with combined glucocorticoid and sex ...

ea0022p23 | Adrenal | ECE2010

Sunitinib decreases adrenocortical cancer cell proliferation and specifically inhibits adrenal steroidogenesis

Reuss Miriam , Kroiss Matthias , Johanssen Sarah , Beyer Melanie , Zink Martina , Hartmann Michaela , Dhir Vivek , Wudy Stefan , Arlt Wiebke , Sbiera Silviu , Allolio Bruno , Fassnacht Martin

Background: The multi-tyrosine kinase inhibitor sunitinib is approved for advanced renal cell carcinoma and gastrointestinal stroma tumors. It targets both tumor vessels and malignant cells. Animal experiments have pointed to a direct adrenotoxic effect of the drug.Aims: We hypothesized that sunitinib may inhibit proliferation of adrenocortical cancer (ACC) cells and influence adrenal steroid hormone synthesis.Results: Sunitinib re...

ea0021p231 | Growth and development | SFEBES2009

Phenotypic presentation of P450 oxidoreductase deficiency during puberty

Idkowiak Jan , O'Riordan Stephen , Reisch Nicole , Dhir Vivek , Malunowicz Ewa , Kerstens Michiel , Maiter Dominique , Collines Felicity , Silink Martin , Dattani Mehul , Shackleton Cedric , Krone Nils , Arlt Wiebke

P450 oxidoreductase (POR) transfers electrons to all microsomal P450 enzymes including CYP21A2 and CYP17A1, key enzymes of glucocorticoid and andogen synthesis, respectively. Mutant POR results P450 oxidoreductase deficiency (ORD) manifesting with glucocorticoid deficiency and disordered sex development in both sexes. Neonatal presentation with undervirilisation in boys and virilisation in girls is well described. However, there is a paucity of data on the pubertal phenotype i...

ea0020p9 | Adrenal | ECE2009

Replicating the normal cortisol circadian rhythm using a formulation of modified-release hydrocortisone

Debono Miguel , Ghobadi Cyrus , Rostami-Hodjegan Amin , Huatan Hiep , Campbell Mike , Newell-Price John , Darzy Ken , Merke DeborahP , Arlt Wiebke , Ross Richard

Background: The adrenal glucocorticoid, cortisol, has a distinct circadian rhythm regulated by the brain’s central pacemaker. This cortisol rhythm acts as a secondary messenger to peripheral tissues and loss of the rhythm is associated with increased morbidity and mortality. This is a specific problem in adrenal insufficiency and congenital adrenal hyperplasia (CAH). Based on pharmacokinetic modelling we have developed a modified-release formulation of hydrocortisone (MR-...

ea0015oc16 | Reproduction | SFEBES2008

Enhanced hypothalamic–pituitary–adrenal axis activation, 5α-reductase activity and insulin resistance distinguishes polycystic ovary syndrome from simple obesity

Vassiliadi Dimitra A , Tomlinson Jeremy W , Hughes Beverly A , Gay Christopher , Sira Shaleen , Nightingale Peter , Shackleton Cedric HL , Stewart Paul M , Arlt Wiebke

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...

ea0015p318 | Steroids | SFEBES2008

Functional and structural characterisation of three CYP21A2 mutations associated with simple virilising and non classic congenital adrenal hyperplasia

Dhir Vivek , Bleicken Caroline , Loidi Lourdes , Parajes Silvia , Quinteiro Celse , Dominguez Fernando , Grotzinger Joachim , Sippell Wolfgang , Riepe Felix , Arlt Wiebke , Krone Nils

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase (CYP21A2) deficiency is the commonest inborn error in steroid hormone biosynthesis and the most frequent cause of congenital adrenal hyperplasia. The classic forms of 21-hydroxylase deficiency, salt-wasting (SW) and simple virilising (SV), usually present in the neonatal period with some simple virilising patients presenting later in childhood with precocious pseudopuberty. The non-classic form (NCCAH) mostly m...

ea0056oc6.1 | Genetic and environmental determinants of obesity and insulin resistance | ECE2018

5β-reductase (AKR1D1) is a potent regulator of hepatic insulin sensitivity, carbohydrate and lipid metabolism in vitro and in vivo

Nikolaou Nikolaos , Gathercole Laura , Marchand Lea , Althari Sara , Green Charlotte , McNeil Catriona , Harris Shelley , van de Bunt Martijn , Arlt Wiebke , Hodson Leanne , Tomlinson Jeremy

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic disease. 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates steroid hormones and, in parallel, catalyzes a fundamental step in bile acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids (BAs) are established regulators of metabolic phenotype. We have hypothesized that AKR1D1 plays a crucial regulatory role in hepatic metabolic homeost...

ea0056p395 | Diabetes (to include epidemiology, pathophysiology) | ECE2018

Hyperandrogenaemia in women with type 1 diabetes mellitus; associations with lipids and lipoprotein particle size, and early vascular disease

Gunness Anjuli , Pazderska Agnieszka , Ahmed Mohamed , McGowan Anne , Phelan Niamh , Boran Gerard , Taylor Angela , O'Reilly Michael , Arlt Wiebke , Moore Kevin , Ann Behan Lucy , Sherlock Mark , Gibney James

Hyperandrogenaemia and polycystic ovary syndrome (PCOS) are common in women with Type 1 diabetes, but it is not known if they contribute to increased cardiovascular risk. We aimed to compare associations between androgen levels, lipid variables and early atherosclerosis in reproductive-age women with and without T1DM. 87 (16 with PCOS) women with T1DM (mean±SD; age 28.7±6.1yrs, BMI 25.4±4.4kg/m2), and 87 (16 PCOS) nondiabetic women (mean±SD; age ...

ea0045oc5.2 | Oral Communications 5- Endocrine | BSPED2016

Functionally significant reductions in white matter in patients with congenital adrenal hyperplasia

Webb Emma , Elliott Lucy , Carlin Dominic , Wilson Martin , Hall Kirsty , Barrett Timothy , Salwani Vijay , Arlt Wiebke , Krone Nils , Peet Andrew , Wood Amanda

Background: Management of patients with CAH remains challenging. There is increasing evidence to suggest that failure to optimize treatment during childhood not only affects final height but also leads to psychological and psychiatric problems, reflecting an underlying effect on neural development. Previous qualitative structural T2-weighted MRI studies have identified white matter hyper-intensities in up to 46% of CAH patients. The nature and functional relevance of these abn...

ea0073oc4.1 | Oral Communications 4: Reproductive and Developmental Endocrinology | ECE2021

Effect of IL-1 receptor antagonism on hyperandrogenemia in women with polycystic ovary syndrome

Popovic Milica , Schiffer Lina , Taylor Angela E. , Arlt Wiebke , Vogt Deborah , De Geyter Christian , Sartorius Gideon , Donath Marc Y. , Christ-Crain Mirjam

BackgroundPolycystic Ovary Syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. The main components are hyperandrogenemia and oligo-/amenorrhea. The pathophysiology of PCOS is not fully understood which is why no causal treatment options are available. A multitude of observational studies demonstrated elevated C-reactive protein (CRP) levels in patients with PCOS compared with weight-matched controls. CRP is a sensitive ...