Prospective study of the value of serum chromogranin A or serum gastrin levels in the assessment of the presence, extent, or growth of gastrinomas

In an interesting study Goebel et al. evaluated serum chromogranin A (CgA) and gastrin in the diagnosis of gastrinoma.1 They concluded that both serum CgA and gastrin were sensitive tumor markers for the detection of a gastrinoma with CgA being the more sensitive, but less specific, test. The latter statement was based on elevated CgA levels in patients with no signs of residual gastrinoma after surgical resection.1 The reason for the apparent rather low specificity of CgA in the diagnosis of gastrinoma in this material could be due to other neuroendocrine tumors in patients with multiple endocrine neoplasia (MEN)-1. The other explanation is that the CgA elevation in patients with gastrinoma is due to enterochromaffin-like (ECL) cell hyperplasia secondary to hypergastrinemia.2, 3 Resection of gastrinoma would not normalize the ECL cell mass or serum CgA immediately. Therefore it would have been of interest to know the time elapsing between the resection of the gastrinoma and the blood sampling. Goebel et al. concluded that serum CgA elevation in patients with gastrinoma was related to the gastrinoma growth and not to ECL cell hyperplasia.1 This conclusion was based on a decrease in serum CgA after resection of the gastrinoma in five patients examined before and after surgery. Again, it would be of interest to know the time lapse between the two samplings because the ECL cell number falls gradually after removal of hypergastrinemia.4 Furthermore, Goebel et al. argued that there was no significant difference in serum CgA levels in patients with or without MEN-1 in spite of previous studies showing more extensive ECL cell proliferation in the latter group.5 However, although ECL carcinoids occur more frequently in patients with hypergastrinemia and MEN-1 than in patients with “spontaneous” gastrinoma, Lehy et al. did not find any significant difference in the argyrophilic cell density in the oxyntic mucosa between these two groups of patients.5 Furthermore, Goebel et al. clearly showed that CgA in the blood increases with serum gastrin up to a level of approximately 1000 pg/mL1 which is the maximum effective concentration of gastrin for stimulating the ECL cell both in the rat6 and humans.7 In the study by Goebel et al. there were two patients who underwent gastrectomy.1 The CgA values in these patients were not mentioned but would have been of great interest. Finally, it has now been demonstrated convincingly that only a proportion of G cells in the antrum contain CgA.8 It also should be recalled that the CgA split product pancreastatin in blood, at least in the rat, is derived mainly from the ECL cell.9 In an interesting and important study on the role of CgA in the assessment of patients with gastrinoma, we believe the authors have misinterpreted the data, which demonstrate convincingly that the main source of CgA in patients with gastrinoma is the ECL cell. Helge L. Waldum M.D., Ph.D.*, Unni Syversen M.D., Ph.D.*, * Department of Inta-Abdominal Diseases, Norwegian University of Science, and Technology, Trondheim, Norway