Endocrine Abstracts

Background: EIF2S3 (NM_001415; Xp22.11) mutations have previously been reported in a single pedigree with microcephaly and developmental delay. The gene encodes the eukaryotic translation initiation factor 2 subunit 3 (eIF2γ), the largest of three EIF2 subunits. EIF2 is a heterotrimeric GTP-binding protein, which initiates protein synthesis. It forms a ternary complex, mediating recruitment of initiator methionyl-tRNA to the 40S ribosomal subunit to scan the mRNA...

Background & Objective: Pseudohypoparathyroidism (PHP), a heterogeneous condition, classically causes parathyroid hormone (PTH) resistance. PHP1a is caused by heterozygous inactivating mutations on the maternally derived GNAS allele. PHP1b results from methylation defects at the GNAS imprinted gene cluster, which are either sporadic, or familial, normally associated with maternally inherited intragenic STX16 deletions. We investigated the presentation, phenotype, ...

Introduction: Monitoring glucocorticoid (GC) replacement in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) remains challenging. There are disease-specific patterns in the plasma and urinary steroid profiles in 21OHD, a key role being played by the 11-oxygenatedC19 androgens. Aim: To explore the urinary steroid profile in 21OHD in relation to treatment and plasma steroids. Methods: Partic...

Introduction: Loss-of-function mutations in IGSF1 result in X-linked congenital central hypothyroidism (CeCH), occurring in isolation or in association with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred.Methods/Design: A novel, hem...

Background: Loss-of-function mutations in IGSF1 result in X-linked congenital central hypothyroidism (CeCH), occurring in isolation or in association with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred.Methods: A novel, hem...

Background: Loss-of-function mutations in IGSF1 result in X-linked congenital central hypothyroidism (CeCH), occurring in isolation or in association with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred.Methods: A novel, hem...

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...

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...

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 ...

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...