Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism

Objectives To characterize the clinical features and insulin regulation in infants with hypoglycemia due to prolonged neonatal hyperinsulinism. Study design Data were collected on 26 infants with hypoglycemia due to neonatal hyperinsulinism that later resolved. Acute insulin response (AIR) tests to calcium, leucine, glucose, and tolbutamide were performed in 11 neonates. Results were compared to children with genetic hyperinsulinism due to mutations of the adenosine triphosphate-dependent potassium (K-ATP) channel and glutamate dehydrogenase (GDH). Results Among the 26 neonates, there were significantly more males, small-for-gestational-age infants, and cesarean deliveries. Only 5 of the 26 had no identifiable risk factor. Hyperinsulinism was diagnosed at a median age of 13 days (range, 2 to 180 days) and resolved by a median age of 181 days (range, 18 to 403 day). Diazoxide was effective in 19 of the 21 neonates treated. In the 11 neonates tested, the AIRs to calcium, leucine, glucose, and tolbutamide resembled those in normal controls and differed from genetic hyperinsulinism due to K-ATP channel and GDH mutations. Conclusions We define a syndrome of prolonged neonatal hyperinsulinism that is responsive to diazoxide, persists for several months, and resolves spontaneously. AIR tests suggest that both the K-ATP channel and GDH have normal function.