Follow-up or surveillance of patients with known or treated carcinoid tumors
An adjunct in the diagnosis of carcinoid tumors
An adjunct in the diagnosis of other neuroendocrine tumors, including pheochromocytomas, medullary thyroid carcinomas, functioning and nonfunctioning islet cell and gastrointestinal amine precursor uptake and decarboxylation tumors, and pituitary adenomas
A possible adjunct in outcome prediction and follow-up in advanced prostate cancer
Specimen Type
Serum
Specimen Requirements
Preferred: Serum Gel
Acceptable: Red Top
Minimum Sample Volume
0.2 mL
Additional Processing Details
Centrifuge and aliquot serum into plastic vial - do not submit in original tube
Required Information
Proton pump inhibitor medications should be discontinued for at least 2 weeks before collection
Stability
Frozen : 90 days
Unacceptable Specimen Conditions
Gross hemolysis
Limitations
Proton Pump Inhibitor Drugs:
Drugs that stimulate secretion of neuroendocrine cells can lead to artifactual chromogranin A (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. In-house data from 1760 specimens suggest that PPI elevate CGA level on average by 757 ng/mL, but a wide range of responses is observed, with some patients showing either lesser, or far greater elevations. 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 falseelevations in CGA.(7)
The use of PPI also compounds the effects of other conditions, listed below, that can result in false-elevations of CGA. In every case, we found that PPI caused additional CGA elevations.
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.
Impaired Hepatic or Kidney Function:
CGA and its peptide fragments are cleared by a combination of hepatic metabolism and kidney excretion. The effects of hepatic failure are relatively minor in the absence of hepatocellular carcinoma or fulminant liver failure. However, even modest kidney impairment can elevate serum CGA, and end-stage kidney failure is associated with elevations (in-house data: mean 471 ng/mL) similar 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 renal function remains stable, in particular because CGA does not seem to change significantly following dialysis (inhouse data, 24 patients; p=0.32). However, results must be interpreted with extreme caution
Non-neuroendocrine Tumors:
As indicated in the Clinical Information, 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. One example is testicular cancer, which in the in-house study was associated with a mean CGA increase of 189 ng/mL.
Limited Agreement Among Different CGA Immunoassays:
There is no universal calibration standard for serum CGA assays. In addition, different CGA assays that use different antibodies or antibody combinations will display different cross-reactivity with the various CGA fragments. Therefore, reference intervals and individual patient results differ significantly between different CGA assays and cannot be directly compared. Serial measurements should be performed with the same assay or, if assays are changed, patients should have their baseline re-established
Test results cannot be interpreted as absolute evidence for the presence or absence of malignant disease
Heterophilic Antibody Interference:
As with all immunometric assays there is a low, but definite, possibility of false-positive results in patients with heterophile antibodies. These antibodies are rarely found in the normal population, but are observed at increased rates in persons with autoimmune disease or after prior sensitization to rodent proteins (eg, patients who have received diagnostic or therapeutic mouse monoclonal antibodies or animal exposure) and in case of immune system activation, such as those found following an infection, in autoimmune disease, or in some cancer patients. Blocking reagents have been added to this assay to minimize the likelihood of heterophile antibody interference. However, test results that do not fit the clinical picture should always be discussed with the laboratory
Spurious False-Low Results Due to "Hook Effect":
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 as it is capable of measuring CGA concentrations in excess of 1,000,000 ng/mL accurately. However, if there is a strong clinical suspicion of hooking, then retesting after further sample dilution should be requested
CGA Fragments Interfering with Accurate Quantification:
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.
