Hyperinsulinaemic hypoglycaemia (HH) is a cause of severe and persistent hypoglycaemia in the newborn period. It is an extremely heterogeneous disorder with respect to clinical presentation, pancreatic histology and molecular biology. The clinical severity of HH varies mainly with age at onset of hypoglycemia (severe hypoglycemia in neonates) and has major consequences in terms of therapeutic outcome and genetic counseling. The commonest genetic cause of persistent HH 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).
Histologically, there are two major subtypes of the disease, namely focal and diffuse. Both the diffuse and focal forms share a similar clinical presentation, but result from different pathophysiological and molecular mechanisms. In addition, diffuse HH usually presents as an autosomal recessive disorder, whereas focal HH is sporadic. Differentiation of diffuse from focal disease is important in terms of management as focal disease requires a limited pancreatectomy (curing the patient) whereas diffuse disease will require a near total pancreatectomy. Imaging with 18F-DOPA-PET/CT is now the gold standard for differentiating diffuse from focal disease. The rapid and accurate diagnosis of HH is very important, as a delay and inappropriate management can lead to brain damage. During the talk I will discuss the clinical presentation and diagnosis of HH. I will outline a management plan and show how advances in molecular biology and radiological imaging techniques have radically changed our approach to these very complex patients.