Genetic and Nongenetic Forms of Hyperinsulinism in Neonates

Abstract

After completing this article, readers should be able to: 1. List the most common cause of persistent hypoglycemia in neonates. 2. Describe identifiable risk factors for hyperinsulinism. 3. List the first-line medical therapy for hyperinsulinism. 4. List nongenetic forms of hyperinsulinism. Hyperinsulinism is the most common cause of persistent hypoglycemia in neonates. Nongenetic forms include transient hyperinsulinism in infants of diabetic mothers and prolonged hyperinsulinism associated with perinatal stress, such as birth asphyxia. Persistent forms of neonatal hyperinsulinism include diffuse disease of the pancreas due to recessive and dominant genetic defects of beta-cell insulin regulation and focal disease due to beta-cell adenomatosis. Hypoglycemia due to hyperinsulinism must be diagnosed promptly and treated vigorously to avoid the risks of seizures or permanent brain damage. This article provides an overview of the genetic and nongenetic forms of neonatal hyperinsulinism and guidelines for diagnosis and treatment. Neonates who have hyperinsulinism can present with tremulousness, lethargy, poor feeding, tachycardia, tachypnea, pallor, hypothermia, and seizures related to the hypoglycemia. These signs of symptomatic neonatal hypoglycemia are nonspecific and are seen commonly in a wide range of other neonatal disorders, including other forms of hypoglycemia, sepsis, and congenital cardiac disease. Because symptomatic hypoglycemia in the neonatal period can be more subtle than in older children, plasma glucose concentrations should be screened in neonates who have risk factors for the various forms of genetic and nongenetic neonatal hyperinsulinism. These risk factors include large-for-gestational age (LGA) or small-for-gestational age (SGA) birthweight, perinatal asphyxia, maternal toxemia or hypertension, maternal diabetes, and high glucose infusion rate (GIR) requirements. Plasma insulin levels often are not clearly elevated in neonates who have hyperinsulinism at the time of hypoglycemia and may be below the level of sensitivity of most assays (2 to 5 mcU/mL [14.4 to 35.9 pmol/L]). Thus, hyperinsulinism is diagnosed best based on physiologic evidence …