Hyperinsulinism causes recurrent and severe hypoglycaemia in the newborn, infancy and childhood period. Although the condition is more common in the newborn period it can present even adults can present with late onset hyperinsulinaemic hypoglycaemia not due to an insulinoma (noninsulinoma pancreatogenous hypoglycemia). Hyperinsulinaemic hypoglycaemia encompasses a heterogeneous group of disorders with respect to clinical presentation, pancreatic histology and molecular biology. The commonest genetic cause of persistent hyperinsulinism are autosomal recessive mutations in the genes ABCC8 and KCNJ11 (encoding the two subunits SUR1 and KIR6.2 respectively) of the pancreatic ATP-sensitive potassium channel (KATP). Defects in these genes cause the most severe forms of hyperinsulinaemic hypoglycaemia which in some cases may require either a limited pancreatectomy (focal form of the disease which will cure the patient) or a near total pancreatectomy (diffuse form with a high risk of diabetes mellitus). Recent advances in imaging techniques such as 18Fluoro-L-Dopa PET (positron emission tomography) have completely changed the management of patients with severe form of hyperinsulinaemic hypoglycaemia as it allows accurately differentiation of focal from diffuse disease. Other rare genetic causes of hyperinsulinaemic hypoglycaemia include mutations in the GCK (glucokinase), GLUD1 (glutamate dehydrogenase), HAHD (SCHAD), HNF4A (hepatocyte nuclear factor 4 alpha), INSR (insulin receptor) and SLC16A1 (monocarboxylate transporter 1) genes. Hyperinsulinaemic hypoglycaemia may also be part of an underlying syndrome (such as Beckwith-Wiedemann, Costello and Kabuki) and multisystem disorders such as congenital disorders of glycosylation (CDG). Hyperinsulinaemic hypoglycemia following gastric bypass surgery for obesity has been reported in several adult patients with pancreatic histological changes similar to infants with persistent hyperinsulinism. The molecular mechanisms leading to the unregulated insulin secretion in these patients are unclear but glucagon like peptide 1(GLP-1) may have a role. During this talk I will give an overview of the different mechanisms leading to hyperinsulinaemic hypoglycaemia in humans.
03 - 07 May 2008
European Society of Endocrinology