Tolbutamide Tolerance

Rationale: This test has been used to establish fasting hypoglycemia and insulin hypersecretion syndromes.1,2 Tolbutamide stimulates the pancreas to produce insulin. This causes the plasma glucose levels of healthy individuals to drop approximately 50% within 30 minutes and return to baseline within two hours. The peak insulin concentration at two minutes does not usually exceed 150 μIU/mL.2


Establishing Hypoglycemia. The average of the glucose values at 120, 150, and 180 minutes (G120-180) can be used to identify patients with fasting hypoglycemia. G120-180 values <55 for lean and <62 for obese subjects are consistent with fasting hypoglycemia. Low G120-180 values can be caused by insulin hypersecretion (ie, insulinoma) but can be secondary to other conditions (eg, liver disease, renal failure, or malnutrition).2,3

Diagnosing Insulinoma. The insulin secretory response is typically exaggerated in patients with hyperinsulinism such as insulinoma. While a number of conditions can result in low G120-180 values, only patients with insulinoma exhibit exaggerated plasma insulin concentrations. Insulin levels >150 μIU/mL at 60 minutes are consistent with insulinoma.1

Protocol: Patient should fast overnight prior to the test. Fasting glucose should be measured prior to initiating test (see note below). Tolbutamide, 1 g (25−40 mg/kg), should be administered as an IV bolus over two minutes. Blood should be collected for glucose and insulin measurements immediately prior to the injection and at 0, 2, 30, 60, 90, 120, 150, and 180 minutes.

Orderable Tests: Insulin, Eight Specimens (014319) (0-, 2-, 30-, 60-, 90-, 120-, 150-, and 180-minute)

Note: The tolbutamide suppression test should not be performed in patients with evidence of hypoglycemia (glucose levels <60 mg/dL) prior to the initiation of the test.1


1. Sacks DB. Carbohydrates. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry.Philadelphia, Pa: WB Saunders; 1999:750-808.

2. McMahon MM, O'Brien PC, Service FJ. Diagnostic interpretation of the intravenous tolbutamide test for insulinoma. Mayo Clin Proc. 1989; 64(12):1481-1488. PubMed 2557494

3. Feldman JM, Blalock JA, Zern RT, et al. Deficiency of dopamine-beta-hydroxylase. A new mechanism for normotensive pheochromocytomas. Am J Clin Pathol. 1979; 72(2):175-185. PubMed 474494


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