Searchable abstracts of presentations at key conferences in endocrinology

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 ...

ea0034p126 | Clinical practice/governance and case reports | SFEBES2014

Double trouble: pseudo-phaeochromocytoma in a patient with adrenocortical cancer

May Christine , Jahagirdar Vidhya , Chortis Vasileios , Jenkins David , Arlt Wiebke , Ayuk John

A 34-year-old male with no significant past medical history presented with severe abdominal pain. On detailed questioning his symptoms included tremors, headache, sweating, and agitation. Despite recent weight gain he had obvious muscle wasting. On admission blood pressure was 166/107 mmHg. Abdominal examination revealed a palpable left upper quadrant mass.CT scan demonstrated a 15 cm mass in the left supernal region with extensive signs of haemorrhage i...

ea0032p1 | Adrenal cortex | ECE2013

Chronocort®, a multiparticulate modified release hydrocortisone formulation, shows dose linearity and twice daily dosing provides physiological cortisol exposure

Ross Richard , Whitaker Martin , Debono Miguel , Huatan Hiep , Arlt Wiebke , Merke Deborah

Cortisol has a distinct circadian rhythm; levels rise from 0300 h to peak within an hour of waking and gradually decline until 1800 h before a quiescent period lasting from 1800 to 0300 h. Current hydrocortisone replacement regimens are unable to replicate this rhythm and we have been investigating modified release technology. Our initial formulation, using tableting technology, demonstrated it was possible to replicate the overnight rise in cortisol but the tablet had reduced...

ea0031p332 | Steroids | SFEBES2013

Truncal fat distribution is associated with enhanced glucocorticoid excretion, increased 5α-reductase activity and higher insulin resistance independent of BMI in women with polycystic ovary syndrome

O'Reilly Michael , Hodson James , Crabtree Nicola , Hazlehurst Jon , Stewart Paul , Tomlinson Jeremy , Arlt Wiebke

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, hyperandrogenism and insulin resistance. Patterns of fat distribution in PCOS may be associated with androgen activation, glucocorticoid metabolism and insulin resistance. Here we analysed the relationship between fat distribution, steroid metabolism and insulin resistance in women with PCOS.We compared results from 100 PCOS patients (Rotterdam criteria) with 80 sex- and BMI-matched con...

ea0028p201 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2012

24-hour urinary glucocorticoid metabolites are associated with hyperinsulinaemia independent of BMI in patients with the polycystic ovary syndrome

O'Reilly Michael , Hazlehurst John , Lebbe Marie , Stewart Paul , Tomlinson Jeremy , Arlt Wiebke

Polycystic ovary syndrome (PCOS) is a triad of insulin resistance, hyperandrogenism and anovulation. PCOS is associated with increased adrenocortical drive and 5alpha-reductase activity, which may have adverse metabolic consequences. Here we analysed the relationship of urinary androgen and glucocorticoid metabolite excretion with markers of insulin resistance in a large PCOS cohort. We compared results from 127 PCOS patients fulfilling Rotterdam diagnostic criteria with 100 B...

ea0028p309 | Steroids | SFEBES2012

Modifying impact of 17-hydroxyprogesterone and sex steroids on mineralocorticoid receptor transactivation by aldosterone

Mooij Christiaan , Parajes Silvia , Arlt Wiebke , Claahsen-van der Grinten Hedi , Krone Nils

Context: Congenital adrenal hyperplasia (CAH) is caused by 21-hydroxylase deficiency in 95% of the cases. This leads to accumulation of steroid precursors prior to the enzymatic block and increased adrenal androgen production; accordingly serum concentrations of 17-hydroxyprogesterone (17OHP), androstenedione and testosterone are elevated in affected patients.Objective: To analyse the effect of 17OHP, androstenedione and testosterone on aldosterone-media...

ea0025oc1.7 | Young Endocrinologists prize session | SFEBES2011

Mutant cytochrome b5 causing 46,XY disorder of sex development (DSD) due to apparent CYP17A1 17,20 lyase deficiency

Idkowiak Jan , Randell Tabitha , Dhir Vivek , Patel Pushpa , Shackleton Cedric H L , Krone Nils , Arlt Wiebke

In humans, androgen synthesis crucially depends on the enzyme CYP17A1 expressed in adrenals and gonads. The 17,20 lyase activity of CYP17A1 catalyses the key step in human androgen biosynthesis, the conversion of 17-hydroxypregnenolone to the universal sex steroid precursor dehydroepiandrosterone (DHEA). For its catalytic activity, CYP17A1 requires electron transfer from P450 oxidoreductase (POR). Mutations in CYP17A1 and POR are known to disrupt human androgen s...

ea0025p229 | Pituitary | SFEBES2011

20 year experience in the surgical management of cushing’s disease in a UK tertiary referral centre

Hassan-Smith Zaki , Johnson Alan , Toogood Andrew , Arlt Wiebke , Sherlock Mark , Stewart Paul

Objective: The past 2 decades have seen advances in the surgical management of Cushing’s disease (CD). Our aim was to meet the need for current data on clinical features, long-term outcomes, and prognostic indicators.Patients and methods: We conducted a retrospective study of 71 patients treated by trans-sphenoidal surgery (TSS) for CD. All patients were operated on by the same surgeon in a single centre between 1988–2009. Diagnosis was confirm...

ea0025p300 | Steroids | SFEBES2011

Concurrent analysis of 10 serum steroids by mass spectrometry: investigation of the viability of the Perkin-Elmer CHS™ MSMS steroids kit on a waters xevo mass spectrometer with acquity UPLC system

Taylor Angela , Shackleton Cedric , Taylor Stuart , Jensen Ulrich Glumer , Ojala Marko , Arlt Wiebke

Steroids present in human serum can be used to identify a number of conditions such as congenital adrenal hyperplasia, Addison’s disease and Cushing’s disorder. Historically this has been completed using immunoassays; currently there is a move towards mass spectrometry which reduces analysis time, cross reactivity and improves sensitivity. When mass spectrometers are coupled with liquid chromatography systems (LC–MS) it is possible to monitor a number of steroid...

ea0021oc3.8 | Young Endocrinologists prize session | SFEBES2009

Identification and functional impact of novel mutations in the gene encoding 11β-hydroxysteroid dehydrogenase type 1 in patients with hyperandrogenism

Lawson Alexander , Walker Elizabeth , Lavery Gareth , Bujalska Iwona , Hughes Beverly , Arlt Wiebke , Ride Jonathan , Stewart Paul

In peripheral target tissues, levels of active glucocorticoid hormones are controlled by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyses the reduction of cortisone to cortisol within the endoplasmic reticulum. For functional 11-ketoreductase activity, 11β-HSD1 requires the NADPH-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH). Loss of 11-ketoreductase activity results in increased cortisol clearance and activation of the HPA axis wi...