The test is useful to distinguish insulinoma vs functional hypoglycemia.


Patient Preparation:

(1) The preparation is the same as for the oral glucose tolerance test.

(2) An intravenous line is started and kept open with normal saline.

(3) The test is contraindicated if patient has a fasting serum glucose of < 50 mg/dL on the day of testing.

(4) The test should be terminated and glucose administered if the patient develops neurological signs of hypoglycemia.


Dose of tolbutamide to administer IV:

(1) newborn: 25 mg/kg given IV diluted in 10 mL sterile saline and given over 2 minutes; alternatively 50 mg/kg orally

(2) adult: 25-40 mg/kg up to 1 gram IV


Specimen collection: Collect serum samples for glucose and insulin, with fasting baseline then 3, 30, 60, 90, 120, 150 and 180 minutes after the tolbutamide administration


In normal patients:

(1) glucose decreases by 60-75% of baseline value at 30 minutes

(2) insulin increases by < 200 microUnits/mL at 3 minutes, then rapidly falls to pre-injection levels by 60 minutes


In diabetics:

(1) glucose values at 30 minutes are > 76% of baseline values


In patients with insulinomas:

(1) plasma glucose levels fall below 50 mg/dL at 30 minutes; plasma glucose levels fail to increase above 57 mg/dL at 120 and 180 minutes

(2) insulin levels increase above baseline and remain persistently high at 120 and 180 minutes

(3) The test may be hazardous to patients if severe hypoglycemia develops.


A discriminant function (DF) can separate patients with insulinoma from normal controls (Service et al, page 422-423), with DF in normals >= 42.5 and in patients with insulinoma < 42.5


DF =

= (glucose at 150 minutes after tolbutamide injection) - (0.5 * (serum insulin level at 150 minutes))


The glucose is lower than normal and remains reduced in:

(1) severe liver disease

(2) acute pancreatitis

(3) malnutrition

(4) azotemia

(5) idiopathic hypoglycemia in children.


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