Hypoglycemia in infants and children can lead to
seizures, developmental delay, and permanent brain damage.
Hyperinsulinism (HI) is the most common cause of both transient and permanent disorders of
hypoglycemia. HI is characterized by dysregulated insulin secretion, which results in persistent mild to severe
hypoglycemia. The various forms of HI represent a group of clinically, genetically, and morphologically heterogeneous disorders.
Congenital hyperinsulinism is associated with mutations of SUR-1 and Kir6.2,
glucokinase,
glutamate dehydrogenase, short-chain
3-hydroxyacyl-CoA dehydrogenase, and ectopic expression on beta-cell plasma membrane of SLC16A1.
Hyperinsulinism can be associated with perinatal stress such as birth
asphyxia, maternal
toxemia, prematurity, or
intrauterine growth retardation, resulting in prolonged neonatal
hypoglycemia. Mimickers of
hyperinsulinism include neonatal
panhypopituitarism, drug-induced
hypoglycemia,
insulinoma, antiinsulin and
insulin-receptor stimulating
antibodies,
Beckwith-Wiedemann Syndrome, and
congenital disorders of glycosylation. Laboratory testing for
hyperinsulinism may include quantification of
blood glucose, plasma
insulin, plasma
beta-hydroxybutyrate, plasma
fatty acids, plasma
ammonia, plasma
acylcarnitine profile, and urine organic
acids. Genetic testing is available through commercial laboratories for genes known to be associated with
hyperinsulinism. Acute
insulin response (AIR) tests are useful in phenotypic characterization. Imaging and histologic tools are also available for diagnosing and classifying
hyperinsulinism. The goal of treatment in infants with
hyperinsulinism is to prevent brain damage from
hypoglycemia by maintaining plasma
glucose levels above 700 mg/L (70 mg/dL) through pharmacologic or surgical
therapy. The management of
hyperinsulinism requires a multidisciplinary approach that includes pediatric endocrinologists, radiologists, surgeons, and pathologists who are trained in diagnosing, identifying, and treating
hyperinsulinism.