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Rationale: This test has been used to diagnose insulin hypersecretion syndromes such as insulinoma.1,2 Failure to produce hypoglycemia (glucose <45 mg/dL) by the end of a 72-hour fast effectively excludes the diagnosis of hypoglycemic disorder.2 When a normal subject becomes hypoglycemic as the result of a prolonged fast, insulin levels generally drop below 6 μU/mL, C-peptide levels drop below 200 pmol/L and proinsulin levels drop below 5 pmol/L. Most patients with insulinoma will become hypoglycemic during this test and will have beta-cell polypeptides greater than the cutoffs listed above.
Further information can be gained by administering glucagon to the hypoglycemic patient. Patients with insulin-mediated hypoglycemia will have increases in glucose >25 mg/dL, while patients with other causes of hypoglycemia will have lower increments.
Protocol (Phase 1): During the fast, the patient is allowed to take in only calorie-free and caffeine-free fluids. Nonessential medication should be withheld, and the patient should be encouraged to be active when awake. Glucose levels should be measured every six hours until the level drops below 60 mg/dL. Samples should then be collected hourly for glucose, insulin, C-peptide, and proinsulin levels. The fast should be concluded when the glucose level drops below 45 mg/dL and the patient exhibits symptoms of hypoglycemia or after a maximum of 72 hours.
Protocol (Phase 2): Perform this phase of the test only if the patient becomes hypoglycemic during phase 1. At the end of phase 1, inject 1 mg of glucagon intravenously and measure glucose levels at 10, 20, and 30 minutes.
Orderable Tests: See Comprehensive List of Procedures section for individual test information.
Note: The patient should be hospitalized during this protocol and intravenous access should be maintained. Glucose should be available for infusion.
1. Service FJ. Diagnostic approach to adults with hypoglycemic disorders. Endocrinol Metab Clin North Am. 1999 Sep; 28(3):519-532. PubMed 10500929
2. Sacks DB. Carbohydrates. In: Burtis CA, Ashwood ER, eds.Tietz Textbook of Clinical Chemistry. Philadelphia, Pa: WB Saunders; 1999: 750-808.