ESPE Abstracts

Primary adrenal insufficiency (PAI) is an important diagnosis to make as it is potentially life-threatening and requires urgent treatment. Although most paediatric endocrinologists have experience of more common conditions such as congenital adrenal hyperplasia (CAH) and autoimmune adrenal insufficiency, more than 30 other genetics causes of PAI exist, as well as physical causes such as haemorrhage. Reaching a specific diagnosis for some of these rarer conditions can have impo...

Congenital adrenal insufficiency is a potentially life-threatening condition that can present soon after birth in many different ways. The classic presentation is a salt-losing crisis due to mineralocorticoid insufficiency, often between a week and two of life, but babies with predominant glucocorticoid insufficiency can present with other features such as prolonged jaundice, hypoglycaemia and hyperpigmentation. Most children with congenital adrenal insufficiency present to em...

Steroidogenic factor-1 (SF-1, NR5A1) is a key regulator of adrenal and gonad development, and controls transcription of many genes in these endocrine axes. A role for SF-1/NR5A1 in human endocrine conditions was first established 15 years ago when rare individuals with adrenal hypoplasia and 46,XY DSD (testicular dysgenesis, Müllerian structures) were reported. Although it was felt that adrenal failure would be a key feature of SF-1 disruption, in the pa...

Background: The presentation of early-onset Primary Ovarian Insufficiency (EO-POI), most often with primary amenorrhea, is at one end of a spectrum spanning 40 years. The aetiology of POI is frequently unclear but next generation sequencing of varied age groups has identified several associated genetic variants. Whether girls with EO-POI are more likely to have a genetic aetiology than those with later presentations remains unknown.<stro...

Background: Heterozygous de novo variants in SAMD9 cause the complex multisystem growth disorder, MIRAGE syndrome. Core features are myelodysplasia, infection, restricted growth, adrenal hypoplasia, genital/gonadal phenotypes, and enteropathy. However, the range of additional associations is expanding and includes disrupted placental development, poor post-natal growth, and other endocrine features. Milder phenotypes are also described, such ...

Introduction: The influence of sex chromosomes and sex hormones on early human brain development is still poorly understood. Expression of Y chromosome genes may influence aspects of brain maturation in the 46,XY fetus, but the contribution of different Y genes is unknown. Furthermore, a marked increase in testicular testosterone biosynthesis/release from the testis occurs at around 8 weeks post conception (wpc) in the 46,XY fetus, but it is unclear whether te...

Background: Primary ovarian insufficiency (POI) is genetically mediated in up to 30% of cases. Many genes associated with POI have roles in early ovary developmental processes, including meiosis.Objectives: We investigated the genetic mechanism underlying early-onset POI in three young women presenting with absent puberty: two sisters from a consanguineous pedigree and a third unrelated proband.<st...

Background: Steroidogenic factor 1 (SF1), encoded by the gene NR5A1, is a member of the orphan nuclear receptor superfamily and important regulator of gonadal and adrenal function. Variations in SF1 lead to a spectrum of conditions including 46,XY DSD, hypospadias, adrenal insufficiency, male factor infertility, and primary ovarian insufficiency. Inheritance patterns can be complicated (e.g. de novo dominant, sex-limited dominant, and autosomal recessive). In...

Introduction: Ovary development was once considered a largely passive process. RNA sequencing (RNAseq) approaches have allowed us to begin to characterise ovary development in previously unparalleled detail, revealing the process to be complex and, still, little understood. A challenge is synthesising and using these data to advance our understanding of clinical disease. Through a clinically-focused lens, we elucidate novel aspects of the transcriptional lands...

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...