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Localization of Insulinomas to Regions of the Pancreas by Intra-arterial Stimulation with Calcium

John L. Doppman; Richard Chang; Douglas L. Fraker; Jeffrey A. Norton; H. Richard Alexander; Donald L. Miller; Elaine Collier; Monica C. Skarulis; and Phillip Gorden
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From the National Institutes of Health and the National Naval Medical Center, Bethesda, Maryland, and Washington University, St. Louis, Missouri. Requests for Reprints: John L. Doppman, MD, Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Building 10, Room 1C660, 10 Center Drive, MSC 1182, Bethesda, MD 20892-1182. Acknowledgments: The authors thank Carla Hendricks, who did the insulin radioimmunoassays and assisted with analysis of the data; Dr. Samuel Wells of Washington University, St. Louis, Missouri, who provided helpful discussion during our selection of the most appropriate secretagogue; and Dr. Charles Lucas of Wayne State University, Detroit, Michigan, who provided surgical and histologic data for one patient.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;123(4):269-273. doi:10.7326/0003-4819-123-4-199508150-00004
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Objective: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas.

Design and Patients: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas.

Setting: Tertiary referral hospital.

Measurements: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9).

Results: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions.

Conclusion: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.


Grahic Jump Location
Figure 1.
Typical sampling results from a patient with an insulinoma in the pancreatic tail.topbottom

Note the eightfold gradient at the 30-second sample from the right hepatic vein ( ) and the rapid decrease in insulin levels at the 60-second sample; this is a frequent, but not invariable, pattern. Lesser gradients are measured in the samples from the left hepatic vein ( ). The conversion factor for insulin levels into pmol/L is 7.175.

Grahic Jump Location
Grahic Jump Location
Figure 2.
In a patient with an insulinoma of the pancreatic head, greater than twofold gradients were seen after calcium injection into both the gastroduodenal and superior mesenteric arteries, with higher elevations in the gastroduodenal artery (top).bottom

Although the gradients in the left hepatic vein ( ) are substantial, the elevations of insulin levels in the right hepatic vein are higher (sixfold) than those in the left hepatic vein (fourfold). The conversion factor for insulin levels into pmol/L is 7.175.

Grahic Jump Location
Grahic Jump Location
Figure 3.
The only nondiagnostic study in the last 20 cases shows elevated insulin levels in the splenic and gastroduodenal arteries.

Although the 30-second gradient is higher in the splenic vein, this is considered a nonlocalizing study. The tumor was found in the body of the pancreas to the left of the superior mesenteric artery. The conversion factor for insulin levels into pmol/L is 7.175.

Grahic Jump Location




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