Tolbutamide Tolerance Test (TTT)

Norm of Tolbutamide Tolerance Test (TTT)

Response to Tolbutamide Administration


Serum Glucose Level


30 Minutes, G30
90–120 Minutes, G90–120
180 Minutes, G180
Serum Insulin Level
Normal 50% below baseline 80%–100% of baseline Baseline Remains ≤150 μIU/mL
Abnormal   40%–64% of baseline   Rapid serum insulin increase above baseline at 10, 20, and 30 minutes.
        >150 μIU/mL at 60 minutes
Fasting hypoglycemia   <55 mg/dL (lean persons)    
    <62 mg/dL (obese persons)    


Usage of Tolbutamide Tolerance Test (TTT)

Helps diagnose insuloma; also used in the differential diagnosis of types of hypoglycemia.


Description of Tolbutamide Tolerance Test (TTT)

There are primarily three types of hypoglycemia: one type that involves an insulin-secreting tumor of the pancreas known as “insulinoma;” one that that is the result of hyperactive islet cells; and a third type that is a result of liver disease. Insulinomas secrete disproportionately high levels of insulin in response to blood glucose levels, causing frequent hypoglycemic episodes. Insulinoma can be diagnosed through this indirect test that administers intravenous tolbutamide, a sulfonylurea that stimulates the pancreas to produce insulin. When administered to a person with insulinoma, there is an exaggerated response, causing abnormally rapid and high insulin levels and abnormally prolonged hypoglycemic response.


Professional Considerations of Tolbutamide Tolerance Test (TTT)

Consent form IS required.

Acute hypoglycemic reaction.
In pediatric or pregnant clients or in clients with baseline glucose levels less than 60 mg/dL.



  1. Tubes: Red topped, red/gray topped, or gold topped. Also obtain ice for the blood sample for insulin measurement.
  2. Obtain baseline blood samples for glucose and insulin levels. Evaluate results before beginning tolbutamide infusion.
  3. Because of the risk of acute hypoglycemia during this test, have oral glucose/rapid-acting carbohydrate and/or 50% dextrose in water available for emergency treatment.
  4. Establish patent intravenous access.
  5. Just before beginning the procedure, take a “time out” to verify the correct client, procedure, and site.



  1. Draw a 3-mL baseline blood sample immediately before tolbutamide injection for glucose in a red-topped tube.
  2. Draw a 7-mL blood sample for insulin immediately before tolbutamide injection in a red-topped, red/gray-topped, or gold-topped tube. Place tube immediately on ice.
  3. Administer tolbutamide 1 g (or 25–40 mg/kg) IV push over 2–3 minutes.
  4. Client should rest comfortably over the next 2 hours while being monitored closely for signs of acute hypoglycemia.
  5. Draw serial glucose and insulin samples at 0, 2, 10, 20, 30, 60, 90, 120, 150, and 180 minutes after the tolbutamide infusion is completed.


Postprocedure Care

  1. Client should eat a meal containing rapid-acting carbohydrates.


Client and Family Teaching

  1. Eat a high-carbohydrate meal for each of the 3 days before this test. Then fast after midnight the night before the test or for at least 8 hours, if the test is not done in the early morning.
  2. This test can take up to 3 hours.


Factors That Affect Results

  1. Concurrent use of beta-adrenergic blockers will diminish response to the test.
  2. Response to tolbutamide may be altered in clients taking MAO inhibitors, sulfonylureas (oxyphenbutazone, phenylbutazone), probenecid, and salicylates.


Other Data

  1. The treatment for insulinoma is surgical removal; the other types of hypoglycemia can often be managed medically.