Pathogenesis and management of hypoglycemia

Glucose is the main substrate utilized by the brain and as such multiple regulatory mechanisms exist to maintain glucose concentrations. When these mechanisms fail or are defective, hypoglycemia ensues. Due to these robust mechanisms, hypoglycemia is uncommon and usually occurs in the setting of the treatment of diabetes using glucose-lowering agents such as sulfonylureas or insulin. The symptoms of hypoglycemia are non-specific and as such it is important to confirm hypoglycemia by establishing the presence of Whipple's triad before embarking on an evaluation for hypoglycemia. When possible, evaluation of hypoglycemia should be carried out at the time of spontaneous occurrence of symptoms. If this is not possible then one would want to create the circumstances under which symptoms occur. In cases where symptoms occur in the post absorptive state, a 72-h fast should be performed. Likewise, if symptoms occur after a meal then a mixed meal study may be the test of choice. The causes of endogenous hyperinsulinemic hypoglycemia include insulinoma, post-bariatric hypoglycemia and noninsulinoma pancreatogenous hypoglycemia syndrome. Autoimmune hypoglycemia syndrome is clinically and biochemically similar to insulinoma but associated with high levels of insulin antibodies and plasma insulin. Other important causes of hypoglycemia include medications, non-islet cell tumors, hormonal deficiencies, critical illness and factitious hypoglycemia. We provide an overview of the pathogenesis and management of hypoglycemia in these situations.