Endocrine Abstracts

The genetic aetiology of central delayed puberty is closely related to the development and function of the gonadotropin-releasing hormone (GnRH) endocrine network. GnRH is the master hormone regulating the reproductive axis and its pulsatile secretion from neurons of the mediobasal hypothalamus is crucial for puberty onset and fertility. Loss-of-function in genes in GnRH neuron pathways can lead to a phenotypic spectrum from self-limited delayed puberty (SLDP) to partial or co...

Introduction: The hypothalamic-pituitary-testicular (HPT) axis is highly active in healthy male newborns until 3-6 months of age. During this phase, namely ‘minipuberty,’ Sertoli cells are stimulated by follicle-stimulating hormone (FSH), increasing testis volume and serum levels of AMH and inhibin B. In addition, luteinizing hormone (LH) promotes testosterone synthesis in Leydig cells, contributing to normal penis size and testicular position in the scrotum. In cong...

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 ...

Introduction: Premature adrenarche (PA) is characterised by elevated adrenal androgens in pre-pubertal children presenting pubic/axillary hair, body odour, greasy hair, and transient growth acceleration. It is still unclear if children with PA are at increased risk of developing metabolic dysfunction or progressing to Polycystic Ovary Syndrome (PCOS) after puberty.Aim: We launched a deep phenotyping study in children with PA from our large, multi-diverse...

Background and Aim: Previous research using data from the I-CAH registry showed wide variation between countries in the provision of glucocorticoid (GC) replacement in congenital adrenal hyperplasia (CAH). In this study, we aimed to establish the impact of different GC doses on height and weight in children and young people with CAH.Methods: Data from children with CAH recorded in the I-CAH registry since 2003 was collected, providing a cohort of 1522 pa...

Background: A genetic cause is found in up to 40% of children presenting with severe short stature and 30% with multiple pituitary hormone deficiency (MPHD) in selected cohorts. Since 2020, to inform diagnosis and tailor management, clinicians may access gene panels provided by three NHS England genomic laboratory hubs (GLHs) as part of the Genomic Medicine Service in England for short stature management: R147 ‘Growth failure in early childhood’ (eligibility: ...

Background: Defects in growth hormone (GH) action account for a substantial percentage of endocrine causes of growth restriction but are frequently unrecognised due to wide clinical and biochemical variability. We report five probands from three families who present with short stature, features of atypical growth hormone insensitivity (GHI), immune dysfunction, atopic eczema, and gastrointestinal pathology associated with recessive variants in QSOX2.<p class="abst...

Introduction: International standards of care for DMD recommend yearly spinal imaging for those on GC and the use of bisphosphonates (BP) for those with symptomatic or moderate asymptomatic vertebral fractures (VF). In view of the significant morbidity associated with VF and the potential for VF cascade, however, there may be justification for prophylactic BP in DMD. Although IV BP are used for treatment, there may be practical and cost advantages of using oral BP prophylactic...

A regional multidisciplinary paediatric DSD clinic has been established in our university hospital since 2006, involving specialists from endocrinology and urology. Selected patients were referred to clinical genetics until 2015, when a clinical geneticist and genetic counsellor joined the DSD team. This was prompted by the increasing recognition of the role of genomics in DSD and availability of an increasingly diverse array of genomic tests through NHS labs. The clinic is he...