Endocrine Abstracts

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...

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...

Cushing’s syndrome due to ectopic ACTH production is extremely rare in childhood. Ectopic ACTH secretion is most often due to tumours in the chest, but rare cases of carcinoid tumours, neuroblastoma, phaeochromocytoma and pancreatic and ovarian carcinoma have been reported. We describe a 2 year old girl with ectopic Cushing’s syndrome due to a malignant epithelial abdominal tumour producing POMC. She presented with rapid weight gain, hypertension, body odour, letharg...

Hereditary stomatocytoses, including cryohydrocytosis, are anaemias in which the erythrocyte membrane has increased permeability resulting in electrolyte leakage and thus haemolysis. Many forms and underlying molecular mechanisms exist. GLUT1 is present in the blood–brain barrier and erythrocytes, but GLUT1-deficiency does not usually affect erythrocytes. We describe a child with a stomatocytosis due to a SLC2A1 mutation presenting with hyperkalaemia, liver disease...

Mutations in GHR, STAT5B and IGF1 lead to GH-insensitivity but often the cause of reduced GH-sensitivity remains unknown. We describe the identification of a mutation in the MVK gene encoding mevalonate kinase (MK) in a pedigree investigated for STAT5B-deficiency.A 15-year-old male born to consanguineous parents was referred for short stature (height 125.8 cm; −5.6 SDS) and arthritis. He presented, aged 2 years, with fev...

Introduction: Pathogenic MC4R variants result in hyperphagia and early onset obesity but puberty is not usually affected. We describe an MC4R variant in a patient with Kallmann syndrome and obesity.Case: A 16 year old male with repaired Tetralogy of Fallot, anosmia, autism and anxiety, was referred with obesity and delayed puberty. Height was -1.31 SDS, BMI 30.7 kg/m2. He had a high arched palate, normal skin, normal hai...

Background: Childhood obesity is the single most pressing public health emergency of the 21st century. The prevalence has increased at alarming rates and globally over 41 million children under 5 years of age are classified as overweight/obese. Overweight and obese children are likely to stay obese as adults and develop multi-morbidities including type 2 diabetes, cancer, non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease at an earlier age. The ava...

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 ...

Somatic activating mutations in BRAF, encoding B-Raf, have been described in tumours and recently craniopharyngiomas. Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include endocrine deficiencies but not craniopharyngiomas. We report three BRAF mutations (two of which are novel) in four children with congenital hypopituitarism. To demonstrate the functional role of the three variants w...

Adamantinomatous craniopharyngiomas (ACPs) are among the most common intracranial tumours in children and they originate from undifferentiated pituitary progenitors. Mutations in the gene encoding for β-catenin (CTNNB1), which lead to the constitutive activation of the Wnt/β-catenin signalling pathway, have been associated with ACP. These tumours can invade adjacent structures, such as the hypothalamus, which makes comp...