Endocrine Abstracts

Background: Abnormal pubertal timing affects over 4% of adolescents and is associated with adverse health and psychosocial outcomes. Previous studies estimate that 60–80% of variation in the timing of pubertal onset is genetically determined. However, despite this strong heritability, little is known about the genetic control of human puberty. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority of patients the neuroendocrine ...

Background: GH insensitivity (GHI) encompasses growth failure, low serum IGF1 and normal/elevated serum GH. IGF1 insensitivity results in pre- and postnatal growth failure with normal/relatively high IGF1 levels.Objective: To undertake candidate gene (CGS) and whole exome (WES) sequencing to obtain a genetic diagnosis in children with short stature and GHI or IGF1 insensitivity.Methods: As a referral centre for GHI genetics, since ...

Background: Homozygous mutations in STAT5B result in GH insensitivity and immune dysfunction. Heterozygous dominant negative mutations have not been described.Aims and objectives: To assess STAT5B sequence in children selected for a phenotype suggestive of Stat5b deficiency. To further characterize genomic STAT5B variants in two families.Methods: Selection of children from a tertiary Paediatric Endocrine ...

Background: Children with hyperinsulinaemic hypoglycaemia (HH) are at a high risk of brain injury, while children with ketotic hypoglycaemia (KH) are believed to be neurologically normal, due to the absence and presence respectively of ketone bodies that act as an alternate fuel during hypoglycaemia. Our objective was to ascertain if children with HH sustain greater white matter (WM) injury in comparison to children with KH.Methods: Neurologically normal...

Background: Congenital, isolated, central, hypothyroidism (CCH), is rare and evades diagnosis on TSH-based congenital hypothyroidism screening programmes in the UK. Genetic ascertainment is therefore paramount in enabling prompt diagnosis and treatment of familial cases. Recognised causes include TSHB and IGSF1 gene defects, with only two previous reports of biallelic, highly disruptive (nonsense; R17X, in-frame deletion and missense; p.S115-T117del+T118), mu...

Background: TMEM38B is a ubiquitously expressed monovalent cation-specific channel protein hypothesized to play a role in intracellular calcium homeostasis. To date, only two unique recessively inherited exon deletions in TMEM38B have been reported in 17 individuals with osteogenesis imperfecta (OI). Data on bone histomorphometry and bone material property have not previously been presented.Cases: Targeted next generation sequencing was performe...

Introduction: Osteonecrosis is an increasingly common complication in young people treated for acute lymphoblastic leukaemia (ALL). This is likely to be due to the now universal use of high dose steroids.Aim: The aim of this study was to obtain information on prevalence, current UK management and long-term outcomes of patients.Methods: We retrospectively collated data on patients with osteonecrosis for the most recently completed t...

Introduction: The World Health Organisation (WHO) states that in an iodine sufficient population <3% of neonatal TSH values will exceed 5 mU/l. In Belgium and Wales 2.6 and 1.5% of values were above 5 mU/l respectively.Methods: Neonatal TSH (neoTSH) levels (AutoDELFIA fluoroimmunoassay, 2006–2013, Scotland) were analysed for prevalence of high value according to cut-off, season and feeding mode (IBM SPSS 22).Results: Out o...

Background: Aortic sized index (ASI) defined as aortic dimensions/body surface area (BSA), has been proposed as a method of identifying aortic dilatation in Turner syndrome. A recent paper reported centile charts of aortic dimensions across for BSA using echocardiogram in 451 children and adults with TS allowing for calculation of Z scores.1Methods: We report Z scores for aortic root adjusted for BSA from clinical echocardiog...

Introduction: Chromosome Xq26.3 microduplications have recently been identified, and explained this 11-year-old girl’s marked tall stature. Her severe phenotype illustrates X-linked acrogigantism (X-LAG) and demonstrates therapeutic benefit from growth hormone receptor blockade.Case: A 5.6-year-old girl presented with growth acceleration from 3 years and appearance of secondary dentition, greasy skin and blackheads from age 4. Past medical and famil...