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Evaluation and Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical Practice Guideline

Washington University School of Medicine (P.E.C.), St. Louis, Missouri 63110; Massachusetts General Hospital and Harvard Medical School (L.A.), Boston, Massachusetts 02114; Barts and the London School of Medicine, Queen Mary University of London (A.B.G.), London E1 2AD, United Kingdom; University of Sheffield (S.R.H.), Sheffield S10 2TN, United Kingdom; University of Minnesota (E.R.S.), Minneapolis, Minnesota 55455; and Mayo Clinic (V.M.M., F.J.S.), Rochester, Minnesota 55905

Address all correspondence and questions: The Endocrine Society, 8401 Connecticut Avenue, Suite 900, Chevy Chase, Maryland 20815. E-mail: govt-prof{at}endo.society.org.

Objective: The aim is to provide guidelines for the evaluation and management of adults with hypoglycemic disorders, including those with diabetes mellitus.

Evidence: Using the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, the quality of evidence is graded very low (), low (), moderate (), or high ().

Conclusions: We recommend evaluation and management of hypoglycemia only in patients in whom Whipple’s triad—symptoms, signs, or both consistent with hypoglycemia, a low plasma glucose concentration, and resolution of those symptoms or signs after the plasma glucose concentration is raised—is documented. In patients with hypoglycemia without diabetes mellitus, we recommend the following strategy. First, pursue clinical clues to potential hypoglycemic etiologies—drugs, critical illnesses, hormone deficiencies, nonislet cell tumors. In the absence of these causes, the differential diagnosis narrows to accidental, surreptitious, or even malicious hypoglycemia or endogenous hyperinsulinism. In patients suspected of having endogenous hyperinsulinism, measure plasma glucose, insulin, C-peptide, proinsulin, β-hydroxybutyrate, and circulating oral hypoglycemic agents during an episode of hypoglycemia and measure insulin antibodies. Insulin or insulin secretagogue treatment of diabetes mellitus is the most common cause of hypoglycemia. We recommend the practice of hypoglycemia risk factor reduction—addressing the issue of hypoglycemia, applying the principles of intensive glycemic therapy, and considering both the conventional risk factors and those indicative of compromised defenses against falling plasma glucose concentrations—in persons with diabetes.

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