Gastrinoma (Zollinger-Ellison Syndrome). In: Oberg K, Couvelard A, Delle Fave G, et al. ENETS Consensus Guidelines for Standard of Care in Neuroendocrine Tumours: Biochemical Markers. Neuroendocrinology. 2017;105(3):201-211.
Gastrinoma (Zollinger-Ellison Syndrome)
From the article: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers
Краткое изложение на русском языке
Gastrinoma (Zollinger-Ellison Syndrome) (pp. 205-206)
Standards for the Diagnosis of a Gastrinoma: Secretin Test
The diagnosis of the Zollinger-Ellison syndrome (ZES) can be established by the demonstration of elevated fasting serum gastrin (FSG) in the presence of low gastric pH. FSG alone is not adequate to make the diagnosis of ZES because hypergastrinemia can be seen in patients with hypo- or achlorhydria associated with chronic atrophic fundus gastritis (e.g., pernicious anemia) and in other conditions with hyperchlorhydria (e.g., Helicobacter pylori infection, gastric outlet obstruction, renal failure, antral G-cell syndromes, short bowel syndrome, and retained antrum). In addition, the use of chronic proton pump inhibitors (PPIs) leads to high FSG levels and, therefore, gastrin provocative tests are needed to establish the diagnosis of ZES. Indeed, in a recent prospective analysis, up to two-thirds of gastrinoma patients were found to have FSG values being <10-fold normal . The gold standard is the secretin test [30–34]. This hormone, when given intravenously, provokes an increase in serum gastrin and, secondarily, in gastric acid secretion. The most reliable data concerning the secretin test have emanated from the National Institutes of Health (NIH) studies in patients with sporadic and multiple endocrine neoplasia type 1-associated gastrinomas [30–34]. Consensus guidelines have described the criteria used for establishing the diagnosis of gastrinoma ; however, according to the expert committee, acid output studies are available to only a limited number of groups (including those expert groups). For the NIH group, the secretin test was useful in diagnosing ZES regardless of the extent or locations of the tumor, the presence or absence of multiple endocrine neoplasia type 1 or the level of FSG (less than or greater than 1,000 pg/mL) . In patients with fasting gastrin <1,000 pg/mL, the sensitivity of the secretin test using the criterion delta (increase from a prestimulation level) gastrin of ≥ 110 pg/mL was 93% (95% CI, 76–99) and for a delta gastrin of 200 pg/mL, sensitivity was 85% (95% CI, 66–96) ( p > 0.05) . The same group recently reported their prospective experience with gastrin provocative tests in 293 ZES patients from the NIH and compared them with 537 ZES patients from the literature and 462 non-ZES patients (again from the literature) . This group established a delta gastrin of ≥ 120 pg/mL in patients with a <10-fold increase as having the highest sensitivity and specificity (94 and 100%, respectively) . They also demonstrated the clear superiority of the secretin provocation test compared to the calcium test (94 vs. 62%). However, in ZES patients with a negative secretin test, the calcium provocation test may be helpful . The expert group noted that certain groups had difficulty in obtaining secretin, hindering accurate diagnosis.
Indications for Gastrin Provocative Tests: Secretin Test
Preparation for Secretin Test
Interpretation of Results
References (p. 210)
30. Berna MJ, Hoffmann KM, Serrano J, Gibril F, Jensen RT: Serum gastrin in Zollinger-Ellison syndrome: I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2,229 cases from the literature. Medicine (Baltimore) 2006; 85: 295–330.
31. Frucht H, Howard JM, Slaff JI, et al: Secretin and calcium provocative tests in the Zollinger-Ellison syndrome. A prospective study. Ann Intern Med 1989; 111: 713–722.
32. Frucht H, Howard JM, Stark HA, et al: Prospective study of the standard meal provocative test in Zollinger-Ellison syndrome. Am J Med 1989; 87: 528–536.
33. Berna MJ, Hoffmann KM, Long SH, Serrano J, Gibril F, Jensen RT: Serum gastrin in Zollinger-Ellison syndrome: II. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and comparison with 537 cases from the literature. Evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features. Medicine (Baltimore) 2006; 85: 331–364.
34. Jensen RT, Niederle B, Mitry E, et al: Gastrinoma (duodenal and pancreatic). Neuroendocrinology 2006; 84: 173–182.
35. Shah P, Singh MH, Yang YX, Metz DC: Hypochlorhydria and achlorhydria are associated with false-positive secretin stimulation testing for Zollinger-Ellison syndrome. Pancreas 2013; 42: 932–936.
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