• When the cause of hypoglycemia is not obvious, the most valuable diagnostic information is obtained from a blood sample drawn during the hypoglycemia. Detectable amounts of insulin during hypoglycemia are abnormal and indicate that hyperinsulinism is likely to be the cause. Inappropriately low levels of free fatty acids, beta-hydroxybutyrate and ketones provide additional evidence of insulin excess. If this critical cannot be obtained during an early episode of spontaneous hypoglycemia, a diagnostic fast may be required.

• An additional piece of evidence indicating hyperinsulinism is an usually high requirement for intravenous glucose to maintain adequate glucose levels. The minimum glucose required to maintain a plasma glucose above 70 mg/dl is referred to as the glucose infusion rate. A GIR above 8 mg/kg/minute in infancy suggests hyperinsulinism. A third form of evidence suggesting hyperinsulinism is a rise of the glucose level after injection of glucagon at the time of the low glucose.

• Once the evidence indicates hyperinsulinism, the diagnostic efforts shift to determining the type. Elevated ammonia levels or abnormal organic acids can indicate specific, rare types. Intrauterine growth retardation and other perinatal problems raise the possibility of transience, while large birthweight suggests one of the more persistent conditions. Evidence for specific type can include responsiveness to some of the therapeutic measures.

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