Laboratory Studies
Due to the elusive nature of the neoplasm, the diagnosis is based on the following three criteria:
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Fasting hypergastrinemia is present (>150 pg/mL with levels >100,000 pg/mL in some patients; a serum gastrin level >1,000 pg/mL in the appropriate clinical setting is virtually diagnostic of Zollinger-Ellison syndrome [ZES]).
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Basal acid output (BAO) is greater than 10 mEq/h.
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Results from a secretin stimulation test are positive.
Fasting serum gastrin measurement is discussed as follows:
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This is the most sensitive test for the diagnosis of ZES.
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This screening test is indicated for patients strongly considered to have a gastrinoma (see History).
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Stop histamine 2 (H2) blockers 1 day or omeprazole 6 days prior to performing the study.
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The reference range for fasting serum gastrin usually is 50-60 pg/mL, with an upper limit as high as 150 pg/mL.
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Levels higher than 1000 pg/mL with acid hypersecretion are highly suggestive of ZES.
Because low gastric acid output (eg, in atrophic gastritis, pernicious anemia, or postvagotomy state) can lead to hypergastrinemia, check patients for the following:
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A gastric pH level higher than 3.0 excludes gastrinoma.
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A BAO of greater than 15 mEq/h and even as high as 150 mEq/h is indicative of gastrinoma.
In patients with intermediate gastrin levels (150-1000 pg/mL) and acid secretion, the secretin stimulation test can help diagnose the presence of gastrinoma. Intravenous secretin (2 U/kg) raises the serum gastrin levels to higher than 200 pg/mL within 2 minutes and, virtually always, within 10 minutes in patients with gastrinomas.
Imaging Studies
Imaging studies are helpful in localizing the tumor. They also are helpful for assessing surgical resectability by helping reveal liver metastasis.
Somatostatin receptor scintigraphy (SRS) is very useful to identify the primary lesions preoperatively. SRS is the most sensitive noninvasive method for localizing the primary tumors and metastases. It also is helpful for detecting the presence of liver or bone metastasis. The findings from this technique can be used to differentiate small liver metastases from small liver hemangiomas. Occasionally, false-positive SRS localization results can occur.
Endoscopic ultrasonography has also been found to be useful in helping to detect the primary tumor, with a reported overall sensitivity and accuracy greater than 90% for intrapancreatic gastrinomas. For extrapancreatic gastrinomas in the duodenal wall, endoscopic ultrasound is useful but somewhat less sensitive.
Computed tomography (CT) scanning and selective angiogram also are helpful in detecting gastrinoma.
Magnetic resonance imaging (MRI) can be used as an adjunct to the imaging studies already discussed. MRI has great value in identifying liver metastases but has not been shown to be useful in detecting extrahepatic tumors less than 1 cm in diameter.
Because of the large proportion of primary gastrinomas in the proximal duodenum, upper endoscopy may also be a useful tool in the localization of tumors in these patients.
Other Tests
Selective arterial secretin injection, involving the gastroduodenal, splenic, and superior mesenteric arteries, with assessment of the hepatic vein serum gastrin concentrations is one among several diagnostic procedures proposed for helping identify gastrinomas. However, this test has been shown to be of value primarily in localizing gastrinomas in the head of the pancreas and proximal duodenum and, therefore, is infrequently recommended.
The calcium infusion test, calcium gluconate, is infused intravenously over 180 minutes with serum gastrin levels obtained at set intervals. In most patients with gastrinomas, this should substantially increase serum gastrin levels (>400 pg/mL increase).
Levels of serum chromogranin A (CgA), a nonspecific marker for neuroendocrine tumors, do not appear to have any value in the diagnosis of gastrinomas compared with alpha-amidated gastrin levels. [8] In a separate study that compared the sensitivity, specificity, and positive/negative predictive values of plasma CgA levels with a polymerase chain reaction (PCR) assay based on a 51-transcript signature to detect neuroendocrine tumors, the PCR-based assay was not only significantly superior to CgA on all performance metrics, but it was also not affected by proton pump inhibitor therapy. [9]
