Introduction

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most important cause of hypoglycemia in early infancy. The inappropriate oversecretion of insulin is responsible for profound hypoglycemia which requires aggressive treatment to prevent severe and irreversible brain damage.

The hyperinsulinism can be classified according to three criteria: (i) the time of onset of hypoglycemia, whether in the neonatal period or later in infancy – this also influences the severity of hypoglycemia; (ii) the histologic lesion, whether it is focal or diffuse – these two forms are not clinically distinct but their surgical treatment differs dramatically. A focal lesion is definitively cured by a limited pancreatectomy whereas a diffuse lesion resistant to medical therapy requires a subtotal pancreatectomy with the high likelihood of subsequent diabetes mellitus; (iii) the mode of genetic transmission, whether it is sporadic, autosomal recessive, or dominant. Diffuse PHHI is most often caused by a recessive gene (particularly the neonatal form) and only rarely a dominant gene. To date, focal lesions have been sporadic.

Physiology of insulin secretion

Hyperinsulinemic hypoglycemia is due to insulin hypersecretion by the islets of Langerhans. Insulin is the only hormone to lower the plasma glucose concentration, which it does by both inhibiting glucose release from hepatic glycogen and increasing glucose uptake in muscle cells. This explains the two main characteristic findings of neonatal PHHI: the high glucose requirement to correct hypoglycemia and the responsiveness of hypoglycemia to exogenous glucagon.