hrp0082p3-d2-963 | Sex Development (1) | ESPE2014

Hypospadias in a Male Patient with 21-Hydroxylase Deficiency and Atypical Clinical Course: Presentation of Two Brothers

Guven Ayla , Hancili Suna , Arlt Wiebke

Introduction: 21-Hydroxylase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia (CAH). Clinical and laboratory findings vary depending on the enzyme activity.Case Report 1: A 2-month-old male infant referred as hypospadias. He was born at term from consanguineous parents with intrauterine growth retardation. The mother had no problem during pregnancy. The external genitalia had penoscrotal hypospadias with chordee and both teste...

hrp0084fc-lb-1 | Late Breaking Abstracts | ESPE2015

RNA Sequencing Reveals the Pathways Perturbed by Redox Imbalance in Nicotinamide Nucleotide Transhydrogenase Null Mice

Meimaridou Eirini , Goldsworthy Michelle , Chortis Vasileios , Foster Paul , Arlt Wiebke , Cox Roger , Metherell Louise

Background: In humans, loss-of-function mutations in Nicotinamide nucleotide transhydrogenase (NNT) cause familial glucocorticoid deficiency, a potentially fatal, adrenal-specific disorder characterized by increased ACTH and reduced cortisol levels. NNT is a highly conserved inner mitochondrial membrane protein, which supplies high concentrations of NADPH for detoxification of reactive oxygen species (ROS) by glutathione and thioredoxin pathways.<p class="abstext"...

hrp0084p2-303 | DSD | ESPE2015

Multiple Malformations Extending the Phenotypic Spectrum of Antley–Bixler Syndrome in a Patient with P450 Oxidoreductase Deficiency due to Two Novel Mutations of the POR Gene

Janchevska Aleksandra , Idkowiak Jan , Caredda Elisabeta , Hurst Jane , Dattani Mehul T , Arlt Wiebke , Spoudeas Helen A

Background: P450 oxidoreductase deficiency (PORD) is characterised by glucocorticoid and sex steroid deficiency and skeletal malformations, resembling Antley–Bixler syndrome (ABS, MIM 124015), a skeletal malformaton phenotype also present in patients with fibroblast growth factor receptor 2 mutations (FGFR2, MIM 176943). While genetic testing confirms both conditions, establishing the exact diagnosis on clinical grounds can be challenging.Objective ...

hrp0086fc1.4 | Adrenals | ESPE2016

Identification of Novel Central Nervous System Imaging Biomarkers Associated with Cognitive Abnormalities 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. 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 abnormalities remains unknown.Objec...

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...

hrp0084p1-62 | DSD | ESPE2015

Prediction of Germ Cell Cancer Occurrence in Postpubertal Individuals with Androgen Insensitivity Based on Pathological Findings and Cancer Predisposition SNPs

Cools Martine , Wolffenbuttel Katja P , Kaprova Jana , Mendonca Berenice B , Drop Sten LS , Hersmus Remko , Stoop Hans , Gillis Ad JM , Costa Elaine MF , Domenice Soraiah , Wunsch Lutsz , Quigley Charmian , Arlt Wiebke , T'Sjoen Guy , Looijenga Leendert HJ

Background: Gonadectomy is generally postponed until early adulthood in complete androgen insensitivity syndrome (CAIS) and close surveillance of gonads in situ proposed in males with partial AIS (PAIS). Delaying gonadectomy further is controversial given the lack of data regarding germ cell cancer (GCC) development in adulthood and the absence of biomarkers for noninvasive GCC screening.Aims and objectives: To study the prevalence of invasive G...

hrp0095p1-5 | Adrenals and HPA Axis | ESPE2022

Urinary steroid metabolite ratios: sex- and age-dependent changes and use for the differential diagnosis of inborn steroidogenesis disorders

S. Baranowski Elizabeth , Guran Tulay , C. Gilligan Lorna , Shaheen Fozia , Utari Agustini , M.H. Faradz Sultana , E. Van Herwaarden Antonius , L. Claahsen - van der Grinten Hedi , E. Taylor Angela , H.L. Shackleton Cedric , Arlt Wiebke

Background: Biochemical ratios of precursor-to-product urinary steroid metabolites have been proposed as surrogate markers of steroidogenic enzyme activity to aid the differential diagnosis of inborn disorders of steroidogenesis. Using ratios rather than total amounts facilitates analysis of single spot urine samples, more convenient than 24-h urine collections for young children. Previous studies examining the utility of these biochemical ratios have been lim...

hrp0084wg3.5 | DSD | ESPE2015

EU-Study: DSD-LIFE

Kohler Birgit , Arlt Wiebke , Bouvattier Claire , de la Perriere Aude Brac , Gaye Claire-Lise , Claahsen-van der Grinten Hedi , Cohen-Kettenis Peggy , Nordenstrom Anna , Pienkowski Catherine , Richter-Unruh Annette , Slowikowska-Hilczer Jolanta , Paris Francoise , Szarras-Capnik Maria , Reisch Nicole , Thyen Ute , Wiesemann Claudia

DSD-LIFE is a comprehensive clinical outcome study investigating medical, surgical, psychosocial, and ethical issues to improve treatment and care of patients with the different diagnoses included in the umbrella term disorders/differences of sex development (DSD). The multidisciplinary DSD-LIFE consortium consists of 15 experienced European scientists in the areas endocrinology, psychology, surgery, gynaecology, urology, and ethics. In 2013 the study protocol and the online d...

hrp0092p1-162 | Adrenals and HPA Axis (1) | ESPE2019

Evaluation of Molecular Characteristics and Steroid Metabolomics in a Large Cohort of Children with 3β-Hydroxysteroid Dehydrogenase 2 Deficiency

Guran Tulay , Kara Cengiz , Yildiz Melek , Bitkin Eda C. , Haklar Goncagul , Lin Jen-Chieh , Gilligan Lorna C. , Barnard Lise , Keskin Mehmet , Anik Ahmet , Catli Gonul , Guven Ayla , Kirel Birgul , Tutunculer Filiz , Onal Hasan , Turan Serap , Akcay Teoman , Atay Zeynep , Baranowski Elizabeth S. , Yilmaz Gulay C. , Mamadova Jamala , Akbarzade Azad , Sirikci Onder , Aghayev AghaRza , Alkan Afra , Shackleton Cedric H.L. , Storbeck Karl H. , Baris Tugba , Arlt Wiebke , Chung Bon-Chu , Bereket Abdullah

Context: Deficiency of 3β-hydroxysteroid dehydrogenase 2 (3βHSD2) causes a very rare form of congenital adrenal hyperplasia (CAH) known as 3βHSD2 deficiency, which is a consequence of biallelic HSD3B2 gene defects. The estimated prevalence is less than 1/1,000,000 live births. Knowledge of comprehensive steroid metabolome patterns in 3βHSD2 deficiency is scarce.Objective: We aimed...

hrp0089p1-p232 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P1 | ESPE2018

Gonadectomy for Adults with DSD Conditions in the International Disorders of Sex Development Registry

Lucas-Herald Angela K , Kyriakou Andreas , Bryce Jillian , Rodie Martina , Acerini Carlo , Arlt Wiebke , Balsamo Antonio , Baronico Federico , Bertelloni Silvano , Brooke Antonia , Claahsen van der Grinten Hedi , Cools Martine , Darendeliler Feyza , Davies Justin H , Desloovere An , Ellaithi Mona , Fica Simona , Gawlik Aneta , Guran Tulay , Hannema Sabine , Hiort Olaf , Holterhus Paul-Martin , Iotova Violeta , Jennane Farida , Lachlan Katherine , Li Dejun , Lisa Lidka , Mazen Inas , Mladenov Wilchelm , Mohnike Klaus , Nedelea Lavinia , Niedziela Marek , Nordenstrom Anna , Poyrazoglu Sukran , Rey Rodolfo , Tadokoro-Cuccaro Rieko , Weintrob Naomi , Faisal Ahmed Syed

Introduction: Depending on the underlying diagnosis, Disorders of Sex Development (DSD) can be associated with an increased risk of germ cell cancers. To date, however, knowledge regarding the indications and timing of gonadectomy is lacking.Methods: The International-DSD (I-DSD) Registry was interrogated for anonymised information regarding the diagnosis, karyotype, sex of rearing and timing of gonadectomy, if undertaken, of all individuals of any karyo...