Endocrine Abstracts

Introduction: The Sonic hedgehog (Shh) pathway is an evolutionarily conserved signalling pathway, playing an essential role during embryonic development. Murine studies have shown the importance of Shh in the growth of the adrenocortical primordium. Shh expression has previously been described in relatively undifferentiated sub-capsular cells in the developing rodent adrenal, however the organisation of the human foetal adrenal (HFA) is unique. This novel study aimed to descri...

The index case, born to non-consanguineous British parents, was born with a normal birth weight. He grew along the −2.9 S.D. centile from the age of 2 years. Eczema was diagnosed at the age of 2 weeks. Investigations at 3–4 years of age showed: IGF1<25 ng/ml, IGFBP3 1.29 (N 0.8–3.9), prolactin 265–653 mU/l (N 59–271), GH peak (glucagon test) 17.3 ug/l, normal GH peaks on overnight sampling, and an IGF1<25 ng/ml...

Familial glucocorticoid deficiency (FGD) results from the inability of the adrenal cortex to produce cortisol in response to ACTH stimulation and can be fatal if unrecognised. The disease manifests clinically with increased ACTH and reduced cortisol levels. Our group has recently demonstrated that oxidative stress is implicated in the pathogenesis of this disorder.We previously identified mutations in nicotinamide nucleotide transhydrogenase (NNT) in pat...

Background: Disturbances of pubertal timing affect >4% of the population and are associated with adverse health outcomes. Studies estimate 60–80% of variation in pubertal onset is genetically determined, but few genetic factors are known. We hypothesise that causal variants will be low-frequency, intermediate-impact variants and will be enriched in populations at the extremes of normal pubertal timing. Families with constitutional delay in growth and puberty (CDGP) ha...

Background: GH resistance or primary IGF1 deficiency (PIGFD) presents with growth failure, low serum IGF1 and normal/elevated serum GH. PIGFD comprises a spectrum of phenotypic and biochemical abnormalities for which genetic GH–IGF1 axis defects may be causative.Objective: Genotyping of PIGFD patients referred for sequencing of candidate genes.Methods: From 2008 to 2013, 62 patients (42 males and 20 females), median age 6.9 ye...

Background: Treatment options for Graves’ disease (GD) and multinodular goitre include antithyroid medication, near total thyroidectomy and radioactive iodine (RAI). RAI is an established treatment for GD in the adult population but is used less commonly in children and the adolescent population due to concerns with regards to safety.Methods: A review of a series of 14 adolescent patients receiving RAI between 2007 and 2013 in our department was per...

Familial glucocorticoid deficiency (FGD, OMIM#202200) is a rare autosomal recessive disorder characterised by adrenal resistance to the action of ACTH, with isolated glucocorticoid deficiency. Recently, mutations in NNT, encoding the mitochondrial anti-oxidant nicotinamide nucleotide transhydrogenase have been reported to cause FGD.Our index case, from a highly consanguineous Kashmiri family, was diagnosed with adrenal insufficiency during a sep...

Background: Pubertal timing has importance both for the individual, but also for public health. Previous studies estimate that 60–80% of variation in pubertal onset is genetically determined. Recently, a large genome-wide association study (GWAS) meta-analysis identified 42 loci for age-at-menarche (AAM), which explained 3.6–6.1% of the variation in the general population, but causal genes have not been identified.CDGP is defined as pubertal on...

Background: GH insensitivity (GHI) presents with growth failure, IGF-1 deficiency and normal/elevated GH (basal >5 μg/l and/or peak >10 μg/l). GHI encompasses a spectrum of clinical and biochemical abnormalities. Associations between phenotypic characteristics and genetic defects remain obscure.Objective: Identify phenotypic predictors of underlying genetic defects in GHI.Methods: In total of 102 children (62M) me...

Short stature (SS), defined as height ≤−2 SDS for a given population, comprises ~50% of new patient referrals to paediatric endocrine clinics. Since >80% SS children in the UK do not receive a clear diagnosis, enhanced genetic testing and stratification is a fundamental need. Whole-genome sequencing (WGS) was offered to rare disease patients recruited to the 100 000 Genomes Project (100KGP), leading to new clinical diagnoses in ~25% of participants. The 100KGP ...