Searchable abstracts of presentations at key conferences in endocrinology

ea0021oc5.3 | Steroids and thyroid | SFEBES2009

Differential roles of PAPSS1 and PAPSS2 in the control of androgen synthesis

McNelis Joanne , Idkowiak Jan , Nogueira Edson , Ward Alexandra , Dhir Vivek , Arlt Wiebke

A key component of androgen synthesis is the availability of the pro-hormone DHEA, which is either converted to active androgens or inactivated to its sulfate ester DHEAS by DHEA sulfotransferase (SULT2A1). The latter reaction requires provision of the universal sulfate donor 3′-phosphoadenosine-5′-phosphosulfate, PAPS. In humans, PAPS is generated by the PAPS synthase isoforms PAPSS1 and PAPSS2. Recently, inactivating PAPSS2 mutations have been identified i...

ea0021p340 | Steroids | SFEBES2009

Steroid replacement: an unusual alternative to oral therapy via 24-h s.c. infusion device

Stewart Sue , Narendon Parth , Hudson Barbara , Hindmarsh Peter , Krone Nils , Arlt Wiebke

Background: Adrenal insufficiency is a well-recognised feature of congenital adrenal hyperplasia (CAH).CAH is commonly treated with oral steroid replacement, taken 2–3 times a day, at doses that aim to reproduce normal diurnal variation. Though acceptable for most patients, this does not control others, resulting in high levels of 17-hydroxyprogesterone-acetate (17OHP), ACTH, and the need for increased doses of steroid replacement, with associated c...

ea0021p364 | Steroids | SFEBES2009

Functional characterisation of 21-hydroxylase gene mutations is a valuable tool for genetic counselling: in vitro and in silico analysis of six novel CYP21A2 sequence variants

Parajes Silvia , Loidi Lourdes , Dhir Vivek , Morey Marcos , Dominguez Fernando , Arlt Wiebke , Krone Nils

Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21OHD) is the commonest inborn error in steroid biosynthesis. It is caused by mutations in the 21-hydroxylase gene (CYP21A2). A good genotype–phenotype correlation exists allowing for prediction of the expressed adrenal phenotype. We performed functional and structural analysis of six novel CYP21A2 variants (p.Trp22Cys; p.Asp184Asn; p.Leu198Phe; p.Val305Gly; p.His310Asn; p.Thr443Asn), i...

ea0016p785 | Thyroid | ECE2008

Isolated ACTH deficiency as a cause of impaired well-being in patients with primary hypothyroidism

Bender Gwendolyn , Cromme Claudia , Hahner Stefanie , Arlt Wiebke , Luster Markus , Reisch Nicole , Reinke Martin , Allolio Bruno

Objective: Isolated ACTH-deficiency (IAD) is considered a rare autoimmune endocrinopathy most frequently associated with autoimmune thyroid diseases (ATD). We have previously diagnosed IAD in four patients with primary hypothyroidism and negative TPO antibodies. The aim of this study was to determine the prevalence of undiagnosed IAD in patients with ATD.Methods: We studied 45 patients with ATD on stable L-thyroxine replacement (dose range...

ea0015p158 | Diabetes, metabolism and cardiovascular | SFEBES2008

Glucocorticoid metabolism in human obesity; increased 5α-reductase activity is associated with insulin resistance in both men and women

Tomlinson Jeremy , Hughes Beverly , Hughes Susan , Vassiliadi Dimitra , Arlt Wiebke , Stewart Paul

The role of endogenous glucocorticoid (GC) production and metabolism in the pathogenesis of obesity, insulin resistance and type 2 diabetes remains unclear. Patients with Cushing’s syndrome develop central obesity, insulin resistance and in some cases type 2 diabetes (T2DM), yet circulating cortisol levels are not elevated in simple obesity. Alterations in GC metabolism, including 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that generates active cortisol ...

ea0015p272 | Pituitary | SFEBES2008

Radiation-induced hypothalamic–pituitary damage in long term survivors of primary brain tumours is reflected by endocrine dysfunction and impaired health-related quality of life

Hammer Fabian , Sherlock Mark , Veit Stefanie , Badent Bettina , Allolio Bruno , Leussink Verena , Arlt Wiebke

Cranial radiotherapy is widely used in combination with chemotherapy to treat patients with primary brain tumours. Increased survival has lead to the recognition of long term sequelae, including endocrine dysfunction due to radiation-induced hypothalamic–pituitary damage. Here we assessed health-related quality of life and endocrine function in 31 adult long term survivors (median age 45, range 29–65 years; 21M, 10F) of primary brain tumours outside the hypothalamic&...

ea0015p274 | Pituitary | SFEBES2008

Use of the morning urinary cortisol to creatinine ratio in the diagnosis of mild Cushing’s disease in patients with discordant test results

Vassiliadi Dimitra A , Holder Geoff , Johnson Alan P , Arlt Wiebke , Stewart Paul M

The diagnosis of Cushing’s syndrome (CS) remains a major clinical challenge especially in a proportion of patients that have discordant results in the available tests. Although the measurement of 24-h urine free cortisol (UFC) is a useful test for the diagnosis of CS, 10–15% of patients have at least one measurement within the normal range and multiple measurements may be required in order to raise its sensitivity. In this study we sought to evaluate the value of the...

ea0015p324 | Steroids | SFEBES2008

Adrenal function testing in 273 patients with severe sepsis reveals baseline cortisol as a reliable predictor of outcome

Mowatt Christopher J , Vassiliadi Dimitra A , Holder Geoff , Clark Penny , Bion Julian , Stewart Paul M , Arlt Wiebke

Stress results in activation of the hypothalamic–pituitary–adrenal axis with increased circulating cortisol. It has been argued that a syndrome of ‘relative adrenal insufficiency’ is common in critically ill patients. Patients who fail to increase their cortisol by >250 nmol/30 min following the administration of 250 μg ACTH in the short synacthen test (SST) have been reported to have a higher mortality (JAMA 2000, 283 1038–1045)...

ea0013oc7 | Society for Endocrinology/Clinical Endocrinology Trust Young Investigator Basic Prize winner | SFEBES2007

Differential effects of P450 oxidoreductase mutants on CYP17 activity provides evidence for an alternative pathway in human androgen biosynthesis

Dhir Vivek , Ivison Hannah E , Krone Nils , Stewart Paul M , Shackleton Cedric HL , Arlt Wiebke

Congenital adrenal hyperplasia (CAH) caused by mutations in the electron donor enzyme P450 oxidoreductase (POR) is unique amongst all CAH variants in that it can be associated with ambiguous genitalia (disordered sex differentiation, DSD) both in 46,XX and 46,XY individuals. POR has a pivotal role in facilitating electron transfer from NADPH to microsomal P450 enzymes, including CYP17, which catalyses a key step in human androgen synthesis, the conversion of 17-hydroxypregneno...

ea0013oc11 | Clinical and translational endocrinology | SFEBES2007

Reduced 5α-reductase activity in peripheral blood mononuclear cells in polycystic ovarian syndrome – a compensatory mechanism for androgen excess?

Hammer Fabian , Bozhinova Nadya , Hughes Beverly A , Fassnacht Martin , Stewart Paul M , Allolio Bruno , Arlt Wiebke

Androgen excess is a key feature of polycystic ovarian syndrome (PCOS). Pre-receptor regulation contributes to this with increased activation of testosterone (T) to 5α-dihydrotesterone (DHT) by 5α-reductase type 1 (SRD5A1), as we have shown previously in PCOS (Lancet 1990,335:431; JCE&M 2003,88:2760). Peripheral blood mononuclear cells (PBMCs) are easily accessible and a useful model for studying pre-receptor regulation in the immune compartment. We have previous...