Endocrine Abstracts

Background: PHID syndrome has been recently described as a unique syndrome characterised by pigmented hypertrichosis; non immune mediated insulin depended diabetes mellitus (DM). Other associated features of the syndrome include pancreatic exocrine insufficiency, short stature and hypogonadism.Aims: To identify the genetic basis of PHID syndrome in six patients from five unrelated families and to characterise the endocrine features associated with this s...

Hypoglycaemia and hypoglycaemia unawareness severely limit the optimal management of diabetes mellitus and cause recurrent morbidity and even mortality in intensively controlled patients. Altered hypothalamic glucose sensing has been implicated in the development of defective counter regulatory responses to insulin induced hypoglycaemia and hypoglycaemic unawareness. This change in hypothalamic glucose sensing has been attributed, at least in part, to an increase in glucokinas...

Background: Hyperinsulinism–hyperammonaemia (HI/HA) syndrome is caused by gain of function mutations in the GLUD1 gene. Patients present with recurrent hyperinsulinaemic hypoglycaemia (HH) together with asymptomatic, persistent elevation of plasma ammonia levels. Leucine sensitivity is an important feature of this condition.Objectives: The aim of this study was to understand the genotype phenotype correlations in patients with HH due to GLUD1 mutati...

Objective: CHI is the most frequent cause of severe hypoglycaemia in infants. Two distinct anatomical forms have been described which require different therapeutic strategies. We evaluated the predictive value and accuracy of integrated [18F]FDOPA-PET/CT as a new tool in identification of focal lesions in an observational study.Patients and methods: From 2005 to 2007, 73 infants and children from the UK (30) and Germany (42) with CHI were exam...

Background: Congenital Hyperinsulinism (CHI) is genetically unexplained today in up to 50% of the patients with persistent or recurrent disease. The uncoupling protein 2 (UCP2) gene is a candidate gene for medical-responsive CHI, since knock out studies have shown that UCP2 deficiency leads to increased glucose-stimulated insulin secretion.Patients and methods: In a large series of 142 patients with transient, persistent or recurrent CHI, we examined for...

Congenital hypoglycemic hyperinsulinemia (CHI) is a clinical and genetic heterogeneous entity. Clinical manifestations can vary from serious life threatening to milder difficultly identifiable cases. Children who don’t react adequate to medical treatment are subject to pancreatic recession. The molecular ethiology are from recessive mutations of the ABCC8 (SUR1) and KCNJ11 (Kir6.2) to dominant mutations of the GCK or GDH genes. Focal dysplasia ...

Hyperinsulinism in Infancy (HI) is a potentially-lethal condition of neonates and during early childhood. For many years the pathophysiology of this disorder was unknown. Recent advances in genetics, histopathology and molecule physiology have now revealed the causes of HI in a large cohort of patients. This review focuses upon the relationship between the basis of HI and current treatment options. From defects in ion channel subunit genes to lesions in the control of pancreat...

ATP-evoked signalling events are known to promote release of insulin from pancreatic beta-cells in a Ca2+-dependent manner. In rodent beta-cells and insulin-secreting cell lines, this is mediated by purinergic receptors and there is evidence for the involvement of both P2X and P2Y subtypes. Here,we have used human insulin-secreting cells to examine the expression of purinoceptors in control and disease tissue. Intact islets and isolated beta-cells were obtained from...

A previously fit and well 27 year old Ghanaian male was brought to hospital by his cousin due to new behavioural changes. The patient was described by his cousin as a normally reserved, self-sufficient man who had become a polar opposite ‘irritable’ personality that ‘spent extravagantly’. He repeatedly claimed to be ‘God’s protection’ and responded aggressively to visual hallucinations. This had resulted in social exclusion and loss of employ...

Introduction: Several previous case reports have described the use of the calcium-blocker Nifedipine for the treatment of hyperinsulinaemic hypoglycaemia (HH). These cases are a collection of transient/permanent forms of HH, with known/unknown genetics, where Nifedipine has been used either as monotherapy or in combination with other medications. There have been no previous reports of any systematic trial of Nifedipine use in patients with HH due to mutations in the ABCC8<...