Searchable abstracts of presentations at key conferences in endocrinology

ea0005s50 | Alternative Careers for Endocrine Researchers | BES2003

Research for clincial paediatric endocrinologists

Blair J , Savage M

Few Paediatric Endocrinologists seek alternative careers on completion of subspeciality training. In addition to developing optimal clinical services, however, opportunities exist to work at the interface of clinical medicine and basic scientific research. Exciting developments in the investigation, diagnosis and treatment of paediatric endocrine patients reflect the success of collaboration between basic scientists and clinicians, paediatricians and adult physicians.Short...

ea0017p35 | (1) | BSPED2008

Maternal uniparental disomy of chromosome 14 and Silver--Russell syndrome: a new genetic association

Dias R , Storr H , Johnston L , Savage M , Clark A

Introduction: Silver–Russell Syndrome (SRS) is a heterogeneous condition characterised by low birth weight, postnatal growth failure and clinical features including relative macrocephaly, limb or facial asymmetry and a triangular facies with broad forehead, pointed chin and downturned mouth. SRS been linked to a number of genetic abnormalities including maternal uniparental disomy (UPD), of chromosome 7 and hypomethylation of the IGF2-H19 imprinted region on chromosome 11...

ea0017p36 | (1) | BSPED2008

Outcomes of screening protocol in children at risk of Von-Hippel Lindau syndrome

Prasad R , Martin L , Savage M , Storr H , Johnston L

Von-Hippel Lindau syndrome (VHL) is a familial disorder presenting in children with a range of different neoplasia. A paediatric screening protocol was published in 2000 and has now been applied to patients in our centre. Screening for VHL is multi-disciplinary involving clinical, biochemical, and radiological investigations.Methods: Data was collected between 2000 and 2007 in 14 children on compliance with screening and identification of pathological le...

ea0019oc25 | Bone and Calcium | SFEBES2009

Genome-wide abnormalities in parental inheritance patterns and DNA methylation in Russell–Silver syndrome

Dias R , Bogdarina I , Johnston L , Buchanan C , Savage M , Hokken-Koelega A , Clark A

Background: Russell–Silver syndrome (RSS) is a heterogeneous condition characterised by pre- and post-natal growth retardation in association with variable dysmorphic features including triangular facies and body asymmetry. The condition has previously been linked to 2 genetic abnormalities: aberrant methylation at the 11p15.5 locus in 30–40% and maternal uniparental disomy (UPD) of chromosome 7 in 10% of cases. Up to 50% of children currently have no identified (epi...

ea0009p59 | Growth and development | BES2005

In vitro demonstration of the effect on RNA splicing of a novel growth hormone receptor mutation

David A , Metherell L , Shaw N , Camacho-Hubner C , Chew S , Savage M , Khoo B , Clark A

Growth hormone insensitivity, also known as Laron Syndrome (LS), is caused by mutations within the GH receptor (GHR). A 1.5 year-old boy with consanguineous parents was referred with postnatal linear growth failure (length 64 cms, minus 6 SDS). Facial features were typical of LS. Investigation revealed elevated serum GH (1145 mIU per litre) and low IGF-I (4 nmol per litre). Genomic DNA was isolated from peripheral blood leucocytes and all GHR exons, including intron-exon bound...

ea0004p72 | Neuroendocrinology and behaviour | SFE2002

Absence of Tpit (Tbx19) gene mutations in patients with late onset Isolated ACTH Deficiency

Metherell L , Savage M , Dattani M , Walker J , Clayton P , Clark A

Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder that is clinically and genetically heterogeneous. Patients are characterised by low or absent cortisol production secondary to low plasma ACTH despite the absence of structural pituitary defects and normal secretory indices of other pituitary hormones. When tested, there is often no ACTH response to exogenous CRH. Onset may occur in the neonatal period, but often is first observed in later childhood. Candid...

ea0045oc6.6 | Oral Communications 6- Endocrine | BSPED2016

Predictive factors of an underlying genetic defect in children with short stature and suspected growth hormone insensitivity (GHI)

Chatterjee Sumana , Shapiro Lucy , Davies Kate M , Savage Martin O , Metherell Louise A , Storr Helen L

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...

ea0036P11 | (1) | BSPED2014

The accuracy of 24-h urinary free cortisol as a screening test in the diagnosis of Cushing's syndrome in children

Shapiro Lucy , Elahi Shezan , Bailey Joe , Martin Lee , Drake William M , Savage Martin O , Storr Helen L

Background: Endogenous Cushing’s syndrome (CS) in children remains a challenge to diagnose and exclude. 24-h urinary free cortisol (UFC) measurements are a convenient, non-invasive test for paediatric patients.Objective: To assess the screening accuracy of 24-h UFC measurements in paediatric patients referred to our centre for evaluation of possible CS.Methods: A retrospective review of children referred to our centre between ...

ea0007p137 | Growth and development | BES2004

Frequency of single nucleotide polymorphisms in the GHRH receptor gene in short children

Smith K , Gueorguiev M , Adams E , Mein C , Johnston L , Bonner S , Froguel P , Savage M , Grossman A , Korbonits M

A number of single nucleotide polymorphisms (SNPs) have been identified in the GHRH receptor gene. Two of these SNPs, A57T and V225I, have been found to cause an increased cAMP response to GHRH stimulation in vitro, and it has been suggested that they may be associated with the abnormal biochemistry in patients with somatotroph adenomas. The objective of this study was to clarify the frequencies of these SNPs in the normal population and in subjects with short stature. The sub...

ea0005p70 | Cytokines and Growth Factors | BES2003

Growth hormone (GH) insensitivity due to a mutation in the cytoplasmic domain of the GH receptor distal to Box 1

Milward A , Metherell L , Maamra M , Wilkinson I , Camacho-Hubner C , Savage M , Ross R , Clark A , Webb S

Background: The majority of patients with GH insensitivity have defects in the extracellular domain of the GHR. We have identified a 47yr old woman homozygous for a 22bp deletion in the cytoplasmic domain of the GHR. The patient had high GH levels, and low IGF-1 of 8 ug/L (normal 54-389 ug/L), IGFBP-3 16nmol/L (normal 61-254 nmol/L) and GHBP 6.8 percent (normal greater than 10 percent) levels. We report functional studies for this mutation (GHR1-449) which results in premature...