hrp0098p1-214 | Adrenals and HPA Axis 3 | ESPE2024

The unique urinary steroid metabolome in infants with P450 oxidoreductase deficiency in the first week of life

S. Baranowski Elizabeth , Idkowiak Jan , Waterson John , D’Harlingue Arthur , H. Olney Ann , E. Ivison Hannah , A. Hughes Beverley , W. Mueller Jonathan , Arlt Wiebke , H.L. Shackleton Cedric

Background: P450 oxidoreductase (POR) is a co-factor critical for the function of type 2 microsomal cytochrome P450 enzymes. POR deficiency (PORD) results in a rare form of congenital adrenal hyperplasia, with combined attenuation of CYP21A2 and CYP17A1 steroidogenic enzymes. It is characterised by combined deficiencies of glucocorticoids and androgens postnatally. Differences in sex development can arise in both sexes due to antenatal activation of the altern...

hrp0095p1-322 | Growth and Syndromes | ESPE2022

Analysis of genetic variability in 134 women with Turner Syndrome using high-throughput next-generation sequencing

P. Suntharalingham Jenifer , Ishida Miho , Cameron-Pimblett Antoinette , M. McGlacken-Byrne Sinead , Del Valle Ignacio , Buonocore Federica , Brooks Anthony , Kaur Madhan Gaganjit , Genomics Sequencing Facility UCL , S. Conway Gerard , C. Achermann John

Background: Turner syndrome (TS) affects 1:2,500 females and results from complete or partial loss of one of the X chromosomes. Typical traits associated with TS include short stature, primary ovarian insufficiency (POI), autoimmune diseases, and cardiovascular and endocrine disorders. Long-term follow-up is needed from the time of presentation into adult life. Several genetic mechanisms have been proposed to account for the development of TS-associated featur...

hrp0092t4 | Top 20 Poster | ESPE2019

Use of Stored Serum in the Study of Time Trends and Geographical Differences in Exposure of Pregnant Women to Phthalates

Henriksen Louise , Mathiesen Barbara , Assens Maria , Krause Marianna , Skakkebæk Niels Erik , Juul Anders , Andersson Anna-Maria , Hart Roger , Newnham John , Keelan Jeffrey , Main Katharina , Pennell Craig , Frederiksen Hanne

Background: There is increasing evidence from epidemiological studies that some man-made chemicals present in the environment can disrupt endocrine homeostasis in exposed humans. Exposure during foetal life to e.g. phthalates has been linked to adverse effects on testicular and ovarian development, thyroid homeostasis and growth in postnatal life. Exposure to phthalates fluctuates not only from day to day but also over time which poses a major challenge for ex...

hrp0089fc15.6 | Growth and Syndromes | ESPE2018

Vosoritide for Children with Achondroplasia:a 30 Month Update from an Ongoing Phase 2 Clinical Trial

Irving Melita , Hoover-Fong Julie , Bacino Carlos , Charrow Joel , Cormier-Daire Valerie , Dickson Patti , Harmatz Paul , Labed Alice Huntsman , Jayaram Kala , Jeha George , Day Jonathan , Larimore Kevin , Phillips John , Savarirayan Ravi

Objectives: Achondroplasia (ACH), caused by a mutation in the fibroblast growth factor receptor 3 gene (FGFR3), leads to inhibition of endochondral bone growth. Vosoritide is a biological analogue of C-type natriuretic peptide (CNP), a potent stimulator of endochondral bone growth. A Phase 2, open-label, sequential cohort, dose-escalation study was conducted to evaluate the safety, tolerability, and efficacy of vosoritide for 24 months in children with ACH aged 5&#150...

hrp0089p1-p216 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology P1 | ESPE2018

SDgeneMatch, A New Tool to Aid the Identification of the Genetic Causes of DSD

De Ridder Jeroen , Bashamboo Anu , Baere Elfride De , Krone Nils , Mitchell Rod , Meyts Ewa Rajpert-De , Tobias Ed , Looijenga Leendert , Achermann John , Werner Ralf , Ahmed Faisal , Hiort Olaf , Greenfiled Andy , McElreavey Ken

Currently, the majority of patients with DSD do not have a molecular diagnosis. Although high throughput sequencing is having an impact on the clinical diagnosis of DSD the accurate interpretation genomic datasets of the identification of new gene mutations causing DSD is challenging. This is due to emerging evidence that DSD may be caused by mutations in many different genes and the prevalence of mutations in a single gene may be very low. As larger number of DSD patients are...

hrp0086fc1.6 | Adrenals | ESPE2016

A Novel Syndrome of IUGR, Congenital Adrenal and Gonadal Insufficiency, Severe Infections, Thrombocytopenia and Monosomy 7 is Caused by SAMD9 Mutations

Buonocore Federica , Kuehnen Peter , Suntharalingham Jenifer , McKee Shane , Didi Mohammed , Brady Angela , Proctor Annie , Ghirri Paolo , Dimitri Paul , Blankenstein Oliver , Knoebl Dieter , Khajavi Noushafarin , Digweed Martin , Grueters Annette , Achermann John

Background: The association of intrauterine growth restriction (IUGR), adrenal insufficiency and gonadal dysgenesis is well recognised. Some children have been reported to develop monosomy 7 and myelodysplasia. However, the genetic basis of this condition was poorly understood.Objective and hypotheses: Our aim was to investigate the genetic basis of eight children with IUGR, adrenal insufficiency and gonadal failure and additional features including seve...

hrp0086fc15.2 | Late Breaking | ESPE2016

Mutations in SGPL1, the Gene Encoding Sphingosine-1-Phosphate Lyase, Cause a Novel Form of Primary Adrenal Insufficiency with Steroid Resistant Nephrotic Syndrome

Prasad Rathi , Maharaj Avinaash , Meimaridou Eirini , VanVeldhoven Paul , Buonocore Federica , Barbagaleta Eliana , Bergada Ignacio , Cassinelli Hamilton , Das Urmi , Krone Ruth , Saleem Moin , Hacihamdioglu Bulent , Sari Erkan , Storr Helen , Achermann John , Guasti Leonardo , Braslavsky Debora , Guran Tulay , Ram Nanik , Metherell Lou

Background: Primary adrenal insufficiency (PAI) is most commonly congenital in children. PAI is genetically heterogeneous with some gene defects causing syndromic disease. A third of patients have no genetic diagnosis meaning their prognosis is uncertain. We recently investigated families with a novel combination of PAI and steroid resistant nephrotic syndrome.Objective and hypotheses: To discover the genetic defect underlying this syndrome.<p class=...

hrp0094fc10.5 | Thyroid | ESPE2021

Adjuvant Rituximab – exploratory trial in young people with Graves’ disease

Cheetham Tim , Cole Michael , Abinun Mario , Alalhabadia Amit , Barratt Tim , Kirk Jeremy , Davies Justin , Dimitri Paul , Drake Amanda , Murray Robert , Steele Caroline , Zammitt Nicola , Carnell Sonya , Howell Denise , Prichard Jonathan , Watson Gillian , Matthews John , Pearce Simon ,

Objective: Remission rates in young people with GravesÂ’ hyperthyroidism are 25% or less after a 2-yr course of thionamide antithyroid drug (ATD). Immunomodulatory agents could potentially improve outcome by facilitating immune tolerance. We wanted to explore whether rituximab, a B lymphocyte depleting agent, would increase remission rates when administered with a short course of ATD.Design: This was an investigator-...

hrp0094p2-406 | Sex differentiation, gonads and gynaecology or sex endocrinology | ESPE2021

ZSWIM7 is associated with human female meiosis and familial primary ovarian insufficiency

McGlacken-Byrne Sinéad M , Le Quesne Stabej Polona , Del Valle Torres Ignacio , Ocaka Louise , Gagunashvili Andrey , Crespo Berta , Moreno Nadjeda , James Chela , Bacchelli Chiara , Dattani Mehul , Williams Hywel J , Kelberman Dan , Achermann John C , Conway Gerard S

Background: Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical consequences. In approximately 10% of cases, POI presents early with absent puberty or primary amenorrhoea. A genetic cause for POI can be found in up to 30% of women. Identified genes often relate to the complex biological processes occurring in fetal life which underpin normal ovary development and function in later adulthood.Objective: We aim...

hrp0097ha1 | An integrated roadmap of human fetal adrenal gland development | ESPE2023

An integrated roadmap of human fetal adrenal gland development

del Valle Ignacio , Young Matthew , Kildisiute Gerda , Ogunbiyi Olumide , Buonocore Federica , Simcock Ian , Khabirova Eleonora , Crespo Berta , Moreno Nadjeda , Brooks Tony , Niola Paola , Swarbrick Katherine , Suntharalingham Jenifer , McGlacken-Byrne Sinead , Arthurs Owen , Behjati Sam , Achermann John

Introduction: The human adrenal gland originates from the adrenogonadal primordium at around 4 weeks post conception (wpc) and undergoes marked developmental changes throughout the first half of pregnancy. Several key aspects of adrenal maturation are well-established, such as the formation of a large inner fetal zone (FZ) and synthesis of dehydroepiandrosterone, but many other processes contributing to adrenal gland development and function in humans are stil...