Searchable abstracts of presentations at key conferences in endocrinology

ea0066oc4.9 | Oral Communications 4 | BSPED2019

Health status of children aged 8–18 years with 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 , Kyriakou Andreas , Ryan Fiona , Crowne Elizabeth , Davies Justin H , Das Urmi , Ahmed S Faisal , Krone Nils

Introduction: There is limited knowledge on the impact of congenital adrenal hyperplasia (CAH) on the health and well-being of children and young persons (CYP). We aimed to establish the health status of CYP with CAH across the United Kingdom.Methods: We conducted a national multi-centre prospective study recruiting 107 patients aged 8–18 with 21-hydroxylase deficiency from 14 centres and 83 matched controls. Demographic, clinical, metabolic data, a...

ea0058oc4.6 | Oral Communications 4 | BSPED2018

Implementation of a novel non-invasive test for monitoring control in individuals with congenital adrenal hyperplasia

Bacila Irina , Acerini Carlo L , Krone Ruth E , Patel Leena , Alvi Sabah , Randel Tabitha , Gevers Evelin F , Dattani Mehul , Cheetham Timothy , Ryan Fiona , Crowne Elizabeth , Davies Justin , Faisal Ahmed , Kyriakou Andreas , Adaway Jo , Schiffer Lina , Keevil Brian , Krone Nils

Introduction: Monitoring of hormonal control represents a key part in the management of congenital adrenal hyperplasia (CAH). It remains suboptimal and relies on frequent blood tests, which are traumatising in children and young persons (CYP). Recent evidence suggests a crucial role of adrenal-derived 11-oxygenatedC19 androgens in the pathogenesis of CAH. Therefore, we aimed to establish a non-invasive test for monitoring of adrenal-specific androgens in CAH.<p class="abst...

ea0033oc2.9 | Oral Communications 2 | BSPED2013

A comprehensive next generation sequencing-based strategy for genetic diagnosis in congenital hypothyroidism

Schoenmakers Nadia , Cangul Hakan , Nicholas Adeline K , Schoenmakers Erik , Lyons Greta , Dattani Mehul , Peters Catherine , Langham Shirley , Habeb Abdelhadi M , Deeb Asma , Puthi Vijith , Park Soo-Mi , Muzza Marina , Persani Luca , Fugazzola Laura , Maher Eamonn , Chatterjee V Krishna

Introduction: Less than 20% of congenital hypothyroidism (CH) has a known genetic aetiology; thyroid transcription factor mutations (PAX8, Nkx2.1, Nkx2.5, FOXE1) or biallelic TSHR mutations cause <5% of thyroid dysgenesis (TD), whereas mutations in genes mediating thyroid hormone biosynthesis (TPO, TG, DUOX2, DUOXA2, IYD, SLC5A5, SLC26A4) account for most dyshormonogenesis cases. Increased CH frequency in consanguineous populations, relatives of ...

ea0030oc2.8 | Oral Communications 2 | BSPED2012

Genetic screening in a large cohort of patients with congenital hypopituitarism; current knowledge and future directions

Alatzoglou Kyriaki S , Turton James P G , Kelberman Daniel , McCabe Marc J , Gregory Louise C , Webb Emma A , McNay David E G , Woods Kathryn S , Mehta Ameeta , Dattani Mehul T

Background and aims: Congenital hypopituitarism (CH) encompasses a spectrum of phenotypes. Known genetic factors account for variable percentage of cases depending on the cohort screened. We analysed the results of genetic screening in a large cohort of patients with CH with the following aims: i) to clarify the genetic aetiology of CH ii) identify any phenotype genotype correlations and iii) propose a screening strategy.Patients and methods: Over 15 yea...

ea0025oc5.3 | Reproduction and fetal programming | SFEBES2011

Mutations in the gene encoding the fibroblast growth factor 8 (FGF8) are associated with complex midline defects including recessive holoprosencephaly and hypothalamo-pituitary dysfunction

McCabe Mark , Gaston-Massuet Carles , Tziaferi Vaitsa , Gregory Louise , Alatzoglou Kyriaki , Signore Massimo , Farooqi Sadaf , Raza Jamal , Walker Joanna , Kavanaugh Scott , Tsai Pei-San , Pitteloud Nelly , Martinez-Barbera Juan-Pedro , Dattani Mehul

Loss-of-function mutations in FGF8 in humans have been associated with Kallmann syndrome (KS), which is characterised by the combination of hypogonadotrophic hypogonadism with anosmia, suggesting that FGF8 is critical for GnRH neuronal development. Interestingly, hypomorphic Fgf8 mutant mice demonstrate poor telencephalic development with deletions of midbrain tissue, absence of olfactory bulbs and optic chiasm, and holoprosencephaly (HPE) with an abnormal corpus...

ea0045p45 | Gonadal, DSD and reproduction | BSPED2016

5-alpha reductase deficiency: insights into the diagnosis and management of a rare condition

Monti Elena , Man Elim , Torpiano John , Rumsby Gill , Carmichael Polly , Storr Helen , Brain Caroline , Buchanan Charles , Conway Gerard , Spoudeas Helen , Mushtaq Imran , Hussain Khalid , Hughes Ieuan , Greening James , Achermann John , Dattani Mehul

Introduction: 5-alpha reductase deficiency (5aRD) is a rare cause of 46XY DSD, that affects sex development before birth and during puberty. The incidence is unknown; affected individuals have been described from all around the world, particularly in small communities or where consanguinity is common.Methods: A 20-year retrospective review of presenting features, biochemical data and genetic analysis of all patients presenting to a single multidisciplina...

ea0104p195 | Reproductive Endocrinology | SFEIES24

Mapping the anatomical and transcriptional landscape of early human fetal ovary development

McGlacken-Byrne Sinead , Del Valle Ignacio , Xenakis Theodoros , Simcock Ian C. , Suntharalingham Jenifer P. , Buonocore Federica , Crespo Berta , Moreno Nadjeda , Liptrot Danielle , Niola Paola , Brooks Tony , Conway Gerard , Dattani Mehul T. , Arthurs Arthurs Owen J. , Solanky Nita , Achermann John

Context: The complex genetic mechanisms underlying human ovary development can give rise to clinical phenotypes if disrupted, such as Primary Ovarian Insufficiency and Differences of Sex Development. In recent years, RNA sequencing (RNAseq) approaches have characterised ovary development in previously unparalleled detail; however, a challenge is synthesising and using these data to advance our understanding of clinical disease.Methods: We combine single-...

ea0103oc5.3 | Endocrine Oral Communications 1 | BSPED2024

Crinecerfont in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: results from the phase 3 CAHtalyst pediatric study

Sarafoglou Kyriakie , Kim Mimi S. , Lodish Maya , Felner Eric I. , Martinerie Laetitia , Nokoff Natalie , Clemente Maria , Fechner Patricia Y. , Vogiatzi Maria G. , Speiser Phyllis W. , Dattani Mehul , B.G. Rosales Gelliza , Roberts Eiry , Jeha George S. , Farber Robert , Chan Jean L.

Background: In phase 2 studies, crinecerfont reduced ACTH and adrenal androgens in adults and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). CAHtalyst Pediatric (NCT04806451, EudraCT 2020-004381-19) is the largest interventional trial to date in pediatric patients with classic CAH.Methods: Male and female participants, aged 2-17 years with elevated androstenedione and 17-OHP and taking GC at doses >12 ...

ea0051oc4.4 | Oral Communications 4 | BSPED2017

The MAPK effector B-Raf is essential for hypothalamic-pituitary axis development and activating mutations in BRAF cause congenital hypopituitarism

Kyprianou Nikolina , Gregory Louise , Vignola Maria Lillina , Nichols James , Marinelli Eugenia , Gualtieri Angelica , Scagliotti Valeria , Besser Rachel , Camper Sally , Davis Shannon , Hogler Wolfgang , Temple Karen , Davies Justin H , Casado Pedro , Rajeeve Vinothini , Cutillas Pedro , Gevers Evelien , Dattani Mehul , Gaston-Massuet Carles

Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include short stature and pubertal delay. The underlying mechanism of endocrinopathies in RASopathies has not been fully elucidated. We report four BRAF mutations (two of which are novel) in four children with congenital hypopituitarism and RASopathy features. To demonstrate the functional role of the variants we performed phosphoproteomic analyses...

ea0081p400 | Pituitary and Neuroendocrinology | ECE2022

European Registries for Rare Endocrine Conditions (EuRRECa): results from the core registry on hypothalamic and pituitary conditions

Luisa Priego Zurita Ana , Appelman-Dijkstra Natasha , Biermasz Nienke , Bryce Jillian , Burman Pia , Castano Luis , Dattani Mehul , Dekkers Olaf M. , Fibbi Benedetta , Gan Hoong-Wei , Gaztambide Sonia , Haeusler Gabriele , Haufler Florentina , Katugampola Harshini , Helene Lasolle , L Muller Hermann , Raverot Gerald , Rica Itxaso , van Beuzekom Charlotte , Sumnik Zdenek , de Vries Friso , Zamanipoor Najafabadi Amir , Ahmed Faisal , M Pereira Alberto

Introduction: The European Registries for Rare Endocrine Conditions (EuRRECa) was created in collaboration with the European Reference Network on Rare Endocrine Conditions (Endo-ERN), the European Society for Paediatric Endocrinology and the European Society of Endocrinology to support the needs of the endocrine community. The Core Registry, one of its platforms, enables the collection of longitudinal patient and clinician reported outcomes. A module collecting aspects of the ...