Hyperinsulinism of infancy: Localization of focal forms

Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children (1). Infants with severe forms of the disorder (formerly termed nesidioblastosis) present with hypoglycemia in the newborn period and are at high risk of seizures, permanent brain damage, and retardation. Infants with congenital hyperinsulinism may have either focal or diffuse abnormalities of the pancreatic β cells. In cases with diffuse disease, an underlying defect in the β-cell adenosoine triphosphate (ATP)-dependent potassium channel may be present, caused by recessive loss of function mutations of the two genes encoding the KATP channel, SUR1 or Kir6.2 (1,2). These mutations may also cause focal hyperinsulinism in which there is an area of β-cell adenomatosis due to loss of heterozygosity for the maternal 11p region and expression of a paternally derived KATP channel mutation (3). Most of the cases with severe hyperinsulinism do not respond to medical therapy with diazoxide, octreotide (Fig. 27B.1), or continuous feedings and require near-total pancreatectomy to control hypoglycemia. However, cases of focal hyperinsulinism can be treated effectively with partial pancreatectomy. The surgical approach and therapeutic outcome for the infants depends on preoperatively distinguishing between focal and diffuse forms of hyperinsulinism. This chapter describes the focal lesions of hyperinsulinism, the pancreatectomy procedure, previous methods of determining the site of focal lesions, and the rationale for using positron emission tomography (PET) scans with ¹⁸F-fluoro-L-DOPA.