Chromogranin A (CgA) is a protein released from neuroendocrine cells, which are specialized cells found throughout the body. Physicians use a blood test to measure CgA levels, using it as a biomarker to provide information about certain biological processes or the presence of a disease. Receiving a test result showing a CgA level over 300 nanograms per milliliter (ng/mL) can be a source of worry, and understanding what this result might mean is the first step in addressing it.
The Significance of CgA as a Biomarker
The primary clinical application for measuring CgA is its function as a tumor marker. It is particularly associated with neuroendocrine tumors (NETs), which arise from the body’s neuroendocrine cells and release CgA into the bloodstream. The concentration of CgA in the blood can correlate with the overall tumor burden, which refers to the total amount of tumor tissue a person has.
Higher levels may suggest a larger tumor or that the disease has spread to other parts of the body. This relationship allows clinicians to use CgA levels for initial detection and for monitoring disease progression or the effectiveness of treatment. It is important to understand that a CgA test is sensitive but not perfectly specific, meaning high levels can be caused by conditions other than NETs. For this reason, an elevated CgA level is not a diagnosis on its own but an indicator that warrants a more thorough investigation.
Cancerous Conditions Associated with High CgA
An elevated Chromogranin A level is most strongly linked to the presence of neuroendocrine tumors. These can develop in many different organs and are often slow-growing. Specific types of NETs that frequently produce high CgA levels include carcinoid tumors, pancreatic NETs, and pheochromocytomas, which are rare tumors of the adrenal glands.
The utility of CgA as a marker can vary depending on the specific type of neuroendocrine tumor, and it is considered a valuable marker for monitoring midgut carcinoid tumors and various pancreatic NETs. While its primary association is with NETs, elevated CgA is sometimes observed in other types of cancer that develop neuroendocrine features. In these contexts, the CgA test is not a primary diagnostic tool but an incidental finding. Examples include certain cases of:
- Small-cell lung cancer
- Prostate cancer
- Breast cancer
- Colon cancer
Non-Cancerous Causes for Elevated CgA Levels
A high CgA reading is not exclusively linked to cancer, as several common non-cancerous conditions and medications can cause levels to rise significantly. One of the most frequent reasons for a falsely elevated CgA result is the use of proton pump inhibitors (PPIs). These medications, including well-known drugs like omeprazole and pantoprazole, are widely prescribed to treat acid reflux. They work by suppressing acid production in the stomach, which in turn stimulates certain stomach cells to release a large amount of CgA.
Beyond medications, various medical conditions can lead to increased CgA levels. Impaired kidney function is a notable cause, as ineffective filtering by the kidneys allows proteins like CgA to accumulate. Chronic atrophic gastritis, a condition involving long-term inflammation of the stomach lining, can also cause a significant rise in CgA. Other health issues include inflammatory bowel disease (IBD), heart failure, and severe infections.
Next Steps After a High CgA Result
Receiving a CgA result over 300 ng/mL prompts a systematic evaluation by a healthcare provider to determine the cause. The process begins with a review of the patient’s medical history and current medications, with a primary focus on proton pump inhibitors (PPIs). If a patient is taking a PPI, the standard approach is to temporarily discontinue the medication for at least two weeks under a doctor’s supervision, after which the CgA test is repeated.
If the CgA level remains high after stopping PPIs, or if these drugs were not a factor, the focus shifts to investigating other non-cancerous conditions. This may involve ordering blood work to check kidney and liver function or other tests related to gastrointestinal health.
Should these initial steps fail to explain the elevated CgA, the investigation will proceed toward ruling out a neuroendocrine tumor. This typically involves a referral to a specialist, such as an endocrinologist or an oncologist. The specialist will likely order advanced imaging studies like a CT scan, an MRI, or a more specialized Gallium-68 DOTATATE PET/CT scan to search for a potential tumor.