This test should not be used for cancer screening or cancer diagnosis. Furthermore, chromogranin A (CgA) is not indicated to be used as a stand-alone monitoring assay and should be used in conjunction with clinical signs and symptoms and other diagnostic evidence. In cases where the laboratory results do not agree with the clinical picture or history, additional tests should be performed.
Test results cannot be interpreted as absolute evidence for the presence or absence of malignant disease.
Drugs that stimulate secretion of neuroendocrine cells can lead to artifactual CgA elevations. In particular, proton pump inhibitors (PPI; eg, omeprazole), which are used in the treatment of esophageal and gastroduodenal ulcer disease and dyspepsia, will result in significant elevations of serum CgA levels, often to many times above the normal range. PPI should therefore be discontinued for at least 2 weeks before CgA measurements because the biological effects of PPI persist for a significant time period after the drugs are discontinued. If absolutely necessary, H2-receptor antagonists at modest doses can be substituted for PPI in such patients without risking significant false-elevations in CgA.(7)
Atrophic gastritis and pernicious anemia also lead to false elevations in serum CgA levels by the same mechanism as PPI, lack of feedback inhibition of gastrin production due to gastric achlorhydria.
CgA and its peptide fragments are cleared by a combination of hepatic metabolism and kidney excretion. Impaired kidney function is associated with elevated serum CgA to similar concentrations to those observed in patients on PPI, making single serum CgA measurements uninterpretable.(8) Serial measurements may have some value in selected patients if the impaired kidney function remains stable, in particular because CgA does not seem to change significantly following dialysis (in-house data, 24 patients; p=0.32). However, results must be interpreted with extreme caution.
Various non-neuroendocrine tumors might be associated with elevations, usually modest, in serum CgA concentrations. This possibility should be considered in patients who are evaluated or followed for neuroendocrine tumors and who show serum CgA elevations that are discordant to the clinical assessment or other biochemical and imaging tests.
Values obtained with different assay methods or kits may be different and cannot be used interchangeably.
In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.
A "hook effect" can occur at extremely high CgA concentrations, resulting in a lower measured CgA concentration than is actually contained in the specimen. This assay is unlikely to be subject to hooking unless CgA concentrations in excess of 1,000,000 ng/mL are present. However, if there is a strong clinical suspicion of hooking, then retesting after further sample dilutions should be requested.
Occasional patient specimens will contain mixtures of CgA fragments that lead to nonlinearity of measurement in specimens with high concentrations of CgA that need to be diluted. It might not be possible to provide an accurate result in some of these individuals.