Endocrine Abstracts

A wide range of disorders must be considered when assessing a child with Short stature (SS). The growth hormone (GH)-IGF-1 axis is essential for normal foetal and childhood growth and defects at many points in the axis will result in growth impairment leading to childhood and adult SS. Severe SS causes physical and psychological disadvantages and the underlying defects may be associated with increased morbidity. Comprehensive investigation of patients with abnormal auxology sh...

Children referred to paediatric endocrinology clinics have variable degrees of short stature and growth failure. There is a wide range of potential aetiologies ranging from normality to an abnormal growth pattern which will lead to adult height below the target height range. Early investigation and diagnosis of short stature is important to prevent delays in the access to appropriate therapies which will improve final height. Genetic variants impacting cellular pathways, hormo...

A three year old boy was referred for surgical correction of an undescended right testis. Intra-operatively he was found to have a hyperplastic right gonad which was in continuation with a unilateral fallopian tube, prompting analysis of his karyotype. This showed 46XX/XY mosaicism with 88% of the cells being XX and 12% XY. The post-operative histology confirmed mixed testicular and ovarian tissue in the right gonad. He appeared phenotypically male and had blaschko lines consi...

Background: Triple A syndrome is a rare, autosomal recessive cause of adrenal insufficiency. Additional features include alacrima, achalasia of the oesophageal cardia, and neurodegenerative disease in 60%. The AAAS gene product is the nuclear pore complex protein ALADIN of unknown function. AAAS patient dermal fibroblasts have been described as hypersensitive to oxidative stress1,2,3.Objective: To establish a better disease model by kno...

Background: Triple A Syndrome is a rare, autosomal recessive cause of adrenal failure that usually manifests in the first decade. Most cases have isolated glucocorticoid deficiency, but this is accompanied by mineralocorticoid deficiency in approximately 10% of cases. Additional features include alacrima (~90%), achalasia of the oesophageal cardia (~75%), and a progressive neurodegenerative process (~60%). The AAAS gene product is the nuclear pore complex protein ALADIN...

Introduction: Triple A syndrome is a rare, autosomal recessive cause of adrenal failure that usually manifests in the first decade. Most cases have isolated glucocorticoid deficiency, but this is accompanied by mineralocorticoid deficiency in ~10%. Additional features include alacrima (~90%), achalasia of the oesophageal cardia (~75%), and a progressive neurodegenerative process (~60%). The AAAS gene product is the nuclear pore complex protein ALADIN of unknown function...

Background: Silver-Russell Syndrome (SRS) is a clinically and genetically heterogenous condition. 40% patients with ‘clinical’ SRS remain without a genetic diagnosis despite fulfilling the Netchine-Harbison Clinical Scoring System (NH-CSS) criteria. There is increasing recognition of the wide range of clinical phenotypes within the SRS spectrum and overlap with other short stature syndromes.Methods: We analysed 26 undiagnosed patients with feat...

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 ...

Primary pigmented nodular adrenal disease (PPNAD) is a form of bilateral adrenocortical hyperplasia characterised by small to normal sized adrenal glands containing multiple small cortical pigmented nodules1. It may occur independently, but 90% of cases are a manifestation of the Carney complex. Most cases of PPNAD are diagnosed before age 30, and are the result of a germline mutation in PRKAR1A or PDE11A, leading to upregulation of cAMP signalling. It is a cause of...

GHI is a genetic condition in which patients present with growth failure due to primary IGF1 deficiency caused by a defect in the GH-IGF1 axis. In the last 10 years in the Centre for Endocrinology of WHRI at Barts and the London, 24 causative mutations in genes of the GH–IGF1 axis have been determined in 58 patients (Table 1). STAT5B mutations were responsible in 2 cases, IGFALS in 4 but the majority of defects identified were in GHR. Most mutations identifi...