Endocrine Abstracts

Introduction: Hyperparathyroidism (HPT) in children is rare with limited outcome measures post surgery.Methods: Retrospective case review of 26 (14M) children (<16 years) who underwent parathyroidectomies (PTx) between 1978 and 2011.Results: Twenty-six children (14M, 12F) included six neonates with neonatal severe HPT (NSHPT) and 20 older children with HPT (13 sporadic, 7 familial).All NSHPT neonates were...

Somatic stem cells of multiple tissues such as brain, blood, gut epithelium and epidermis, have specific roles in tissue homeostasis and plasticity of cell types. There is evidence that when mutated, such cells, termed cancer stem cells (CSCs) also underlie tumorigenesis, but their presence in many tumours is elusive. In the pituitary gland, somatic stem cells (PSCs) have been previously identified and characterised but little is known about their role in tumorigenesis. Adaman...

Introduction: Thyroid nodules in children are more often malignant than in adult practice (~26 vs 5–10%) and in our locality the incidence of thyroid cancer in young people is increasing. We therefore assessed the presentation, investigation, histology and management of paediatric patients presenting with thyroid nodules.Methods: This was a retrospective audit conducted at a regional unit (catchment population ~3 million) where young people are like...

Introduction: Thyroid hormones act via receptors encoded by different genes (THRA and THRB) generating receptor subtypes (TRα1, TRβ1, TRβ2) with differing, tissue-specific expression. Resistance to thyroid hormone due to THRB defects is well recognised, but no THRA mutations have yet been reported. We describe the first case of human TRα-mediated thyroid hormone resistance due to a dominant negative THRA mutation.<p cl...

Introduction: Glucocorticoid replacement therapy uses twice or thrice daily regimens of hydrocortisone (HC) with variable distribution of the dose over the day. Deconvolution analysis determines the mass of hormone that needs to be secreted to attain a particular serum concentration. We have used this methodology to determine the amount and distribution of cortisol over a 24 h period.Methods: Seventy-nine adults (41M) aged 60–74 years and 30 childre...

Familial glucocorticoid deficiency (FGD;OMIM 202200) results from the inability of the adrenal cortex to produce cortisol in response to ACTH stimulation. Half of all cases are caused by mutations in MC2R, MRAP or STAR. SNP array genotyping of FGD patients of unknown aetiology mapped a disease locus to chromosome 5p13-q12. Targeted exome sequencing of 5p13-q12 in one patient identified a homozygous mutation, p.Ala533Val, in nicotinamide nucleotide transhyd...

Introduction: Release of GH by the somatotroph cells of the anterior pituitary is stimulated by GHRH. GHRH acts via its transmembrane receptor, GHRHR, a G-protein coupled receptor that stimulates protein kinase A. Recessive mutations in GHRHR are associated with severe isolated GH deficiency (IGHD) with a final height in untreated patients between 130±10 cm (−7.2±1.6 SDS) and 114±0.7 cm (−8.3±0.1 SDS) in males and females respectively.</p...

Introduction: Loss-of-function mutations in PROK2 and PROKR2 in humans have been associated with Kallmann syndrome (KS), characterised by the combination of hypogonadotrophic hypogonadism with anosmia, suggesting that both are critical for GnRH neuronal development.Objective: KS has overlapping phenotypes and genotypes through FGF8 and FGFR1 with congenital hypopituitarism including septo-optic dysplasia (SOD) and thus we aime...