hrp0092fc10.1 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Investigating the Roles of Androgens in Male Reproductive Development, Maintenance and Function by Characterisation of Androgen and Cortisol Deficient 11ß-Hydroxylase Mutant Zebrafish Lines

Oakes James A , Storbeck Karl-Heinz , Cunliffe Vincent T , Krone Nils P

The zebrafish is established as an important model system for studying development and disease, and characterisation of the developmental and functional roles of steroids is crucial for its effective employment in this remit. Whilst oestrogens are known to be essential for female development in zebrafish, the roles of androgens in the development, maintenance and function of the male reproductive system remain unclear.In order to investigate these proces...

hrp0092fc15.3 | Late Breaking Abstracts | ESPE2019

The P450 Side-Chain Cleavage Isozyme Cyp11A2 Facilitates Interrenal and Gonadal Steroid Hormone Biosynthesis in Developing and Adult Zebrafish

Li Nan , Oakes James A , Storbeck Karl-Heinz , Cunliffe Vincent T , Krone Nils P

Cytochrome P450 side-chain cleavage enzyme, encoded by the CYP11A1 gene, catalyzes the first and rate-limiting step of steroid hormone biosynthesis. Previous morpholino knockdown studies described the divergent functions of the two cyp11a paralogs in zebrafish. Cyp11a1 has been suggested to be required for early development, whereas cyp11a2 is a functional equivalent of human CYP11A1 and is essential for the initiation and maintenan...

hrp0094p1-110 | Adrenal B | ESPE2021

Current Management Of Acute Adrenal Insufficiency Related Adverse Events In Children- Results Of An International Survey Of Specialist Centres

Ali Salma R. , Bryce Jillian , Krone Nils P. , Grinten eHedi L. Claahsen-van der , Ahmed S. Faisal ,

Background: >There is a wide variation in the reported rate of acute adrenal insufficiency (AI) related adverse events (sick day episodes and adrenal crises) between centres.Objective: Evaluate the level of consensus on the criteria that should be considered ‘essential’ for defining and managing adverse events associated with acute AI in children.Methods: Three groups of ...

hrp0092p1-6 | Adrenals and HPA Axis | ESPE2019

Health status of children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency in the United Kingdom: results of a multi-centre cohort study

Bacila Irina-Alexandra , Mahdi Sundus , Acerini Carlo L , Krone Ruth , Patel Leena , Alvi Sabah , Randell Tabitha , Gevers Evelien , Dattani Mehul , Cheetham Timothy , Kyriako Andreas , Ryan Fiona , Crowne Elizabeth , Davies Justin H , Ahmed S. Faisal , Krone Nils P

Introduction: Congenital adrenal hyperplasia (CAH) is associated with long-term health problems. However, little is known about co-morbidities and their onset in children and young persons (CYP).Objective: To establish the health status of CYP with CAH across the United Kingdom.Methods: A multi-centre prospective study recruited 102 patients with 21-hydroxylase deficiency targeting...

hrp0092rfc13.2 | Adrenals and HP Axis | ESPE2019

Development of Novel Non-Invasive Strategies for Monitoring of Treatment Control in Patients with Congenital Adrenal Hyperplasia

Bacila Irina-Alexandra , Adaway Jo , Hawley James , Mahdi Sundus , Acerini Carlo L , Krone Ruth , Patel Leena , Alvi Sabah , Randell Tabitha , Gevers Evelien , Dattani Mehul , Cheetham Timothy , Kyriakou Andreas , Schiffer Lina , Ryan Fiona , Crowne Elizabeth , Davies Justin H , Ahmed S Faisal , Keevil Brian , Krone Nils P

Introduction: Glucocorticoid treatment remains a challenging aspect in the management of congenital adrenal hyperplasia (CAH). Current strategies for monitoring treatment are suboptimal and rely largely on frequent blood tests, which are traumatising in children and young persons (CYP). Recent evidence indicates a crucial role of 11-oxygenatedC19 androgens in the pathogenesis of CAH.Aim: To explore the use of 11-oxygenat...

hrp0092p1-10 | Adrenals and HPA Axis | ESPE2019

Global Practice of Glucocorticoid and Mineralocorticoid Treatment in Children and Adults with Congenital Adrenal Hyperplasia – Insights from the I-CAH Registry

Bacila Irina-Alexandra , Blankenstein Oliver , Neumann Uta , van der Grinten Hedi L Claahsen , Krone Ruth , Acerini Carlo , Bachega Tania SS , Miranda Mirella C , Mendonca Berenice , Birkebaek Niels H , Cools Martine , Milenkovic Tatjana , Bonfig Walter , Tomlinson Jeremy , Elsedfy Heba , Balsamo Antonio , Hannema Sabine , Higham Claire , Atapattu Navoda , Lichiardopol Corina , Guran Tulay , Abali Zehra , Mohnike Klaus , Finken Martijn JJ , Vieites Ana , Darendeliler Feyza , Guven Ayla , Korbonits Marta , de Vrie Liat , Costa Eduardo , Einaudi Silvia , van der Kamp Hetty , Iotova Violeta , Ross Richard , Faisal Ahmed S , Krone Nils P

Introduction: Despite existing guidelines there is no unified approach to glucocorticoid and mineralocorticoid replacement in congenital adrenal hyperplasia (CAH). Consequently, treatment varies in adults and children as well as across countries.Objective: We used data from the I-CAH Registry to identify geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids of children and adul...

hrp0094p2-19 | Adrenals and HPA Axis | ESPE2021

Genetic analysis of paediatric primary adrenal insufficiency of unknown aetiology over 25 years

Buonocore Federica , Maharaj Avinaash , Qamar Younus , Koehler Katrin , Suntharalingham Jenifer P. , Chan Li F. , Ferraz-de-Souza Bruno , Hughes Claire R. , Lin Lin , Prasad Rathi , Allgrove Jeremy , Andrews Edward T. , Buchanan Charles R. , Cheetham Tim D. , Crowne Elizabeth C. , Davies Justin H. , Gregory John W. , Hindmarsh Peter C. , Hulse Tony , Krone Nils P. , Shah Pratik , Shaikh Mohamad G. , Roberts Catherine , Clayton Peter E. , Dattani Mehul T. , Thomas N. Simon , Huebner Angela , Clark Adrian J. , Metherell Louise A. , Achermann John C. ,

Introduction: Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that requires appropriate diagnosis and treatment. The most common cause of PAI is congenital adrenal hyperplasia (CAH), but other well-established aetiologies include metabolic and autoimmune disorders, and physical damage. Mutations in more than 30 genes have now been associated with PAI, with considerable biochemical and phenotypic overlap. It is therefore importan...

hrp0082p3-d2-967 | Sex Development (1) | ESPE2014

Phenotypic and Genotypic Variability of Patients with 5-α Reductase Type 2 Deficiency

Hu Kun , Krone Nils , Kirk Jeremy

Background: Steroid 5-α reductase type 2 (SRD5A2) deficiency is an rare inherited disorder resulting from mutations in the SRD5A2 gene, causing 46,XY DSD (Disorder of Sex Development). The mutated SRD5A2 enzyme can no longer convert testosterone to dihydrotestosterone, which is needed for virilisation of external genitalia.Objective and hypotheses: To describe the phenotype, investigations and management of SRD5A2 deficiency.<p class="a...

hrp0089rfc1.4 | Adrenals &amp; HPA Axis | ESPE2018

Mass Spectrometry-Based Assessment of Childhood Androgen Excess in 487 Consecutive Patients Over 5 Years

Idkowiak Jan , Elhassan Yasir S , Mannion Pascoe , Smith Karen , Webster Rachel , Saraff Vrinda , Barrett Timothy G , Shaw Nick J , Krone Nils , Dias Renuka P , Kershaw Melanie , Kirk Jeremy , Krone Ruth E , O'Reilly Michael W , Arlt Wiebke

Background: Androgen excess in childhood is a common clinical presentation and might signify serious pathology. We have recently explored patterns and severity of androgen excess in a large female adult cohort to differentiate common polycystic ovarian syndrome (PCOS) from non-PCOS pathology, including congenital adrenal hyperplasia (CAH), ovarian hyperthecosis and adrenal and ovarian tumours (Elhassan et al., JCE&M 2018). Herein, we undertake a similar approach f...

hrp0082fc1.3 | Adrenal | ESPE2014

Genetic Engineering Using TALENs to Study the Redox Regulation of Steroidogenesis in vivo

Griffin Aliesha , Parajes Silvia , Taylor Angela , Mueller Ferenc , Krone Nils

Background: Transcription activator-like effects nucleases (TALENs) have recently been developed as an efficient method for in vivo genome engineering. Zebrafish are becoming an increasingly popular model to study translational aspects in endocrinology. The redox cofactor ferredoxin (FDX1) is essential for mitochondrial cytochrome P450 (CYP) enzymes including those required for steroidogenesis. In vitro, FDX1 modifications influence the catalytic rate of ster...