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As a first approximation, the mnemonic that I use for the differential diagnosis of fasting hypoglycemia in an adult is based on the word "EXPLAIN." "EX" refers to exogenous drugs, such as insulin, sulfonylureas, and alcohol. "P" indicates pituitary insufficiency. "L" denotes liver failure and a variety of enzyme deficiencies that affect hepatic glycogenolysis and gluconeogenesis. "A" is for adrenal insufficiency. "I" initially represented islet-cell tumors or hyperplasia but with the description of two new syndromes it also stands for immune-mediated hypoglycemia associated with anti-insulin receptor antibodies and spontaneously occurring anti-insulin antibodies. We more commonly associate such antibodies with insulin resistance, but antibodies of both types have been accompanied by severe hypoglycemia. In vitro antireceptor antibodies are acutely insulinomimetic, which may explain their ability to produce hypoglycemia. "N" refers to neoplasms, nonpancreatic.
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