Endocrine Abstracts

There are a range of screening and diagnostic tests for the investigation of short stature, some of which are unpleasant and even dangerous for the patient. Growth hormone (GH) heterogeneity and wide assay biases cause additional complications for interpretation of results. We have used questionnaires to assess protocols and practice in the investigation of short stature by paediatricians and clinical biochemists in Wales.Responses from laboratory staff ...

A well-term baby born to consanguineous healthy Yemenese parents was observed in the hospital as parents had lost previous three babies (both male and female) within 10 days of age (in Yemen). These babies who were initially well were reported to have developed a rash and then collapsed and died. Post-mortems were not done. This baby who appeared well at birth, also developed a facial rash on day seven and was found to have hyponatremia and severe hyperkalemia, albeit a normal...

Corepressors and coactivators mediate thyroid hormone receptor-dependent repression and transactivation of positively-regulated target genes respectively, but their role in negative regulation is not understood.A 4 years old boy was born at 31 weeks. He was jittery at birth, with neonatal respiratory distress. Childhood features included poor weight gain, heat intolerance, tachycardia and hyperactivity. Ongoing problems are low frequency hearing loss, po...

Neonates harbouring germline gain-of-function TSHR mutations (M453T, L629F) have been reported with transient proptosis. This resolves once euthyroidism is achieved. In contrast children expressing TSHR mutations (V597L, I486T) fail to thrive, with weight gain and height between the 0.4th and 2nd centiles. We have previously demonstrated TSHR expression in preadipocytes undergoing adipogenesis. We now investigate the consequences of constitutively active TSHR mutation expressi...

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 individuals. Rapid detection and treatment by neonatal screening and administration of T4, is essential to prevent severe mental retardation and impaired growth.We report on two Welsh siblings, detected by neonatal screening, which had normal sized and placed glands but negative isotope uptake. Mutations resulting in CH are known to occur in 11 known genes, given the clinical presentation, we investigated the...

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 individuals. Rapid detection by neonatal screening and T4 administration is essential to prevent severe mental retardation and impaired growth. About one third of CH is due to mutations in known genes including the thyrotropin receptor (TSHR).Two Welsh male siblings with CH were detected, both had normally sized and located thyroid glands, no iodide uptake and were negative for thyroid bloc...

A child with short stature having height greater than 2 standard deviations below the mean for age and bone age delay of two years but with normal growth hormone secretion tests was identified. Since there was no known clinical cause of the short stature, it was decided to sequence both alleles of the patient's GH1 gene that encodes pituitary GH to determine whether there was a genetic defect responsible for the observed phenotype (with local ethical approval). A 3.2kb fragmen...

The pituitary-expressed growth hormone 1 gene was screened for mutation in a group of 74 Spanish children with familial short stature resulting in the identification of a novel Ile179Met missense mutation. Variant and wild-type GH were expressed in insect cells and functional studies were performed. The Ile179Met variant was shown to exhibit a similar degree of resistance to proteolysis as wild-type GH, indicating that the introduction of Met does not cause significant ...

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...