Protean manifestations of neonatal hyperinsulinism

Endogenous hyperinsulinism is the leading cause of persistent hypoglycemia in children under one year of age. Classically, the symptoms of neonatal hypoglycemia have been referable to central nervous system dysfunction, with seizures described in nearly all patients. Our experience with eight neonates emphasizes the protean manifestations of this disease. One patient presented with a maternal history of diuretic use, and developed asymptomatic hyperinsulinism documented by provocative testing. The hyperinsulinism cleared after two weeks of medical therapy. This transient hyperinsulinism may have been secondary to use of a thiazide-type diuretic. A second patient presented, as a neonate, with a large abdominal mass but no seizure activity. Exploratory laparotomy revealed an 11 x 5 x 3 cm pancreatic tumor, which required splenectomy, 60% gastrectomy and duodenectomy for removal. Histologic examination demonstrated an insulin-secreting hamartoma. A third patient died suddenly without prior symptoms, and was found to have striking nesidioblastosis on pathologic examination. One infant presented with absence of the abdominal musculature (prune belly syndrome) and features of the Beck-with-Wiedeman syndrome, as well as profound hypoglycemia. Only three patients had seizures, and an additional patient had jitteriness. Pathologic diagnoses were: nesidioblastosis (n = 2); islet cell hyperplasia (n = 1); adenoma (n = 1); hamartoma (n = 1); transient hyperinsulinism (n = 1). One patient's pancreas showed areas of nesidioblastosis, islet cell hyperplasia, and a discrete adenoma in the region of the common bile duct. Careful diagnostic testing is essential in these patients, inasmuch as hypoglycemia is poorly tolerated by neonates and infants. Using the diagnostic algorithm presented here, all patients' endogenous hyperinsulinism was documented quickly and efficiently. Recognition of the broad spectrum of symptoms with which these patients may present is essential if serious neurologic sequelae are to be avoided.