Searchable abstracts of presentations at key conferences in endocrinology

ea0019oc10 | Neuroendocrine and Steroids | SFEBES2009

PAPSS2 deficiency: a novel monogenic cause of androgen excess

Dhir V , Noordam C , McNelis J , Schlereth F , Hanley N , Krone N , Smeitink J , Smeets R , Sweep F , Claahsen-van der Grinten H , Arlt W

Androgen excess is a key feature of the polycystic ovary syndrome; however the molecular mechanisms underlying its pathogenesis largely remain elusive. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in the human circulation but only unconjugated dehydroepiandrosterone (DHEA) can be converted to active androgens. Conversely, conversion of DHEA to its sulfate ester DHEAS by DHEA sulfotransferase, SULT2A1, diminishes the DHEA pool available for androgen gener...

ea0019p337 | Steroids | SFEBES2009

The role of serum and urinary steroids in the monitoring of adults with congenital adrenal hyperplasia

Reisch N , Krone N , Hughes B A , Vassiliadi D A , Flade L , Bidlingmaier M , Shackleton C H L , Stewart P M , Arlt W

Glucocorticoid treatment in congenital adrenal hyperplasia (CAH) is a continuous challenge, with even the experienced clinician struggling to strike the right balance between glucocorticoid over- and undertreatment. There is no consensus on monitoring of glucocorticoid therapy in adults with CAH. Some recommend a serum 17-hydroxyprogesterone (17OHP) target range of 12–36 nmol/l prior to glucocorticoid morning dose. Here we investigated the value of serum and urinary stero...

ea0029s57.1 | What's new in congenital adrenal hyperplasia (CAH)? | ICEECE2012

Congenital adrenal hyperplasia: counselling from birth to the next generation

Krone N.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders causing deficient cortisol synthesis. The commonest cause, 21-hydroxylase deficiency, accounts for about 90–95% of cases. Other entities such as deficiencies of 11β-hydroxylase, 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase type 2, and P450 oxidoreductase are considerably rarer. The differential diagnosis has to be established as different forms of CAH will require different...

ea0029p9 | Adrenal cortex | ICEECE2012

Progressive adrenal insufficiency in a patient with 46,XY DSD caused by two novel mutations in the cytochrome P450 side-chain cleavage (CYP11A1) gene

Parajes S. , But B. , Chan A. , Rose I. , Taylor A. , Griffin A. , Dhir V. , Arlt W. , Krone N.

Background: Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individua...

ea0032p2 | Adrenal cortex | ECE2013

Impaired quality of life in CAH adults is associated with adiposity and insulin resistance

Han TS , Krone N , Willis DS , Conway GS , Rees DA , Stimson RH , Walker BR , Arlt W , Ross RJ

Background: Quality of life (QoL) has been variously reported as normal or impaired in congenital adrenal hyperplasia (CAH) adults. We found impaired QoL in UK CAH adults (Arlt et al. Journal of Clinical Endocrinology and Metabolism 2010 95 5110–5121) and now report the relationship between QoL (SF-36) and health outcomes in these patients.Methods: Cross-sectional analysis of 151 CAH adults with 21-hydroxylase defi...

ea0029p8 | Adrenal cortex | ICEECE2012

Defining 17α-hydroxylase in zebrafish: expression pattern of two paralog genes (zCyp17a1; zCyp17a2) and comparative in vitro and in silico analysis

Parajes S. , Griffin A. , Miguel Escalada I. , Rose I. , Taylor A. , Sacco L. , Grotzinger J. , Arlt W. , Mueller F. , Krone N.

Background: Zebrafish is emerging as a comprehensive model system in endocrinology. Zebrafish synthesise steroid hormones in the interrenal (counterpart of the mammalian adrenal), gonad and brain. Data on steroidogenic pathways is patchy and steroidogenic enzymes in zebrafish have not been well characterised. Human 17α-hydroxylase (hCYP17A1) facilitates two conversion steps, 17α-hydroxylase and 17,20-lyase reactions in the adrenal and gonad. Two zCyp17a (zCyp17a1; zC...

ea0024op1.4 | (1) | BSPED2010

Differences in metabolic effects of twice daily versus multiple daily insulin injections in children with type 1 diabetes

Abid N , Buckley G , Porter L , Day E , Davies P , Shaw N , Kirk J , Krone N , Hogler W , Barrett T

Introduction: Two insulin regimes are commonly used in type 1 diabetes (T1D): twice daily (BD) premixed insulin (short and intermediate acting), and multiple daily injections (MDI) of short acting insulin with once daily bolus of long acting insulin. MDI is associated with better glucose control in adults, but the evidence base is weaker for children.Objectives: We aimed to compare children started on MDI to BD from diagnosis, on HbA1c as a measure of gl...

ea0019p88 | Clinical practice/governance and case reports | SFEBES2009

Quality of life in adult patients with congenital adrenal hyperplasia – results of the congenital adrenal hyperplasia adult study executive

Krone N , Willis D , Hahner S , Wild S , Allolio B , Ross R , Arlt W , CAH Adult Study Executive CaHASE

Congenital adrenal hyperplasia (CAH) represents the most common inborn metabolic error and is associated with significant morbidity and mortality. There is a paucity of clinical data in adult patients, a lack addressed by congenital adrenal hyperplasia adult study executive (CaHASE), a multicentre cross-sectional study of the health status of adults with CAH that recruited 203 patients from 17 centres (54% of patients contacted). Psychometric evaluation was assessed by validat...

ea0017p24 | (1) | BSPED2008

Characterisation of seven novel 11β-hydroxylase (CYP11B1) gene mutations: three severe and four mild mutations

Parajes S , Loidi L , Rumsby G , Kirk J , Cole T , Conway G , Quinkler M , Dominguez F , Arlt W , Krone N

Congenital adrenal hyperplasia (CAH) is one of the most common autosomal recessive disorders. About 5–8% of cases are caused by the deficiency of steroid 11β-hydroxylase (CYP11B1) due to mutations in CYP11B1 gene. CYP11B1-inactivating mutations can be found without particular hot-spot spread over the entire gene. A good phenotype-genotype correlation exists for the patients suffering from 11β-hydroxylase deficiency (11OHD). The prediction of diseas...

ea0039ep72 | Gonadal, DSD and reproduction | BSPED2015

The role of a next generation sequencing panel in the diagnostic pathway in disorders of sex development

Webb Emma A , Saraff Vrinda , Hughes Lowri , Allen S , Cole Tim , Dattani M T , Hughes I A , Kirk J M W , Fews G , Krone N P

Background: Accurate genetic diagnosis is essential in disorders of sex development (DSD), guiding medical management and enabling optimal personalized care delivery.Case presentation: Two siblings (I and II) with a family history of 17β-hydroxysteroid dehydroxygenase (17β-HSD3) deficiency presented postnatally with isolated labial swelling. Karyotype was 46,XY and urinary steroid profile (USP) normal. HCG-stimulated testosterone/androstenedion...