Costello syndrome is characterized by mental retardation, loose skin, coarse 
facies, skeletal abnormalities, cardiovascular abnormalities (congenital heart 
defects, cardiomyopathy, rhythm disturbances), and predisposition to neoplasia. 
Endocrine abnormalities including growth hormone deficiency, adrenal 
insufficiency, glucose intolerance, parathyroid adenoma with hyperprolactinemia 
and hypoglycemia have been described. Hypoglycemia has been documented due to 
growth hormone and cortisol deficiency. We report on two patients with Costello 
syndrome and persistent hyperinsulinemic hypoglycemia and review the endocrine 
manifestations of Costello syndrome. Both patients required diazoxide therapy to 
stop the unregulated insulin secretion and maintain normoglycemia. The mechanism 
of persistent hyperinsulinism in patients with Costello syndrome is unclear.