Provocative Tests

For patients in whom the diagnosis of insulinoma is suspected but other tests have been normal or equivocal, provocative tests may be used.13 A brief description of such tests follows.

Glucagon Test

Glucagon stimulates the release of glucose from liver glycogen stores, thereby producing a rise in blood glucose levels. A baseline glucose level is obtained, and then 1 mg of glucagon is injected intramuscularly. Serum glucose levels are then obtained at 15 minutes, 30 minutes, and subsequent 30-minute intervals for 3 hours. Normally, there is a rapid rise in serum glucose levels during the first hour, with a return to fasting glucose levels by 3 hours. Reactive hypoglycemia does not occur. In the presence of an insulinoma, however, there is a greater than normal rise in the glucose levels, followed by severe hypoglycemia in the presence of elevated levels of insulin. This test is positive in 72% of patients with insulinomas.

Glucose Tolerance Test

A glucose tolerance test may also indicate the presence of an insulinoma. Fifty grams of glucose in 100 mL of water is given orally and serum glucose levels are measured at 0, 30, 60, 90, 120, and 180 minutes. Normally, the peak glucose level is reached by 1 hour, and does not exceed 160 mg/dL. The normal serum fasting glucose level is regained at 2 hours. Patients harboring an insulinoma have an exaggerated hypoglycemic phase during which glucose levels may fall 20 mg/dL or more below fasting levels and remain depressed for several hours. Symptoms of hypoglycemia may be present. This test is noted to be positive in 60% of insulinoma patients.

Calcium Infusion Test

Kaplan and colleagues demonstrated that infusion of calcium results in a rise of serum insulin, C peptide, and proinsulin levels in patients with an insulinoma17 (Fig. 79-5). In this study, calcium was infused at a concentration of 5 mg/kg per hour, and hypoglycemia was noted to occur within 2 hours. In normal individuals, glucose and insulin levels remain normal in response to calcium infusion. More recently, this

ITcalcium ^lucpnotej


Plasma glucose #

mg/IOOml 50.

Serum Insulin 100 ^U/ml 5.

Serum calcium

mg/100 ml

Time (minutes)

FIGURE 79-5. Calcium infusion test. A patient with a well-differentiated malignant insulinoma experienced hypoglycemic symptoms nearly IV2 hours after the start of the calcium infusion (*). Insulin levels increased maximally at 30 minutes, which was accompanied by a threefold increase in proinsulin (shaded bar). (From Kaplan EL, Rubenstein AH, Evans R, et al. Calcium infusion: A new provocative test for insulinomas. Ann Surg 1979;190:501.)

test has been modified. A rapid intravenous calcium injection may be used preoperatively to confirm the diagnosis of insulinoma,18 or calcium may be infused intra-arterially as part of a localization study. This approach is described in greater detail subsequently.19 Calcium stimulation tests are used in infants with nesidioblastosis as well.

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