Chromogranin A (CgA) is a protein found in the bloodstream that functions as an important biomarker in medical diagnostics. Its concentration is measured through a simple blood test. While not part of routine blood work, CgA measurement is a specialized diagnostic tool used when conditions involving the endocrine system are suspected, helping guide clinical management.
The Biological Role of Chromogranin A
CgA is a member of the granin family of proteins, synthesized primarily in neuroendocrine cells. These specialized cells share characteristics of both nerve cells and hormone-producing endocrine cells. They are distributed widely throughout the body, including in glands like the adrenal medulla, pituitary, and thyroid, as well as the gastrointestinal tract. CgA is stored within secretory granules alongside various hormones and neuropeptides before being released into the circulation.
The primary function of CgA is that of a pro-hormone, which is broken down into several smaller, biologically active peptides. Examples of these derived peptides include vasostatin, pancreastatin, and catestatin. These fragments have diverse regulatory functions, influencing the cardiovascular, immune, and endocrine systems.
For instance, pancreastatin inhibits insulin secretion, while catestatin regulates blood pressure and cardiac function. A low level of the intact protein and its fragments is always present in the blood because CgA is constantly processed and released by healthy neuroendocrine cells. When these cells proliferate abnormally, they secrete excessive amounts of CgA, making the protein measurable in the bloodstream.
Clinical Indications for CgA Testing
The CgA blood test is primarily ordered when a physician suspects a neuroendocrine tumor (NET), a rare cancer originating from neuroendocrine cells. NETs commonly arise in the gastrointestinal tract, pancreas, and lungs. Measuring CgA is a general, non-specific marker because nearly all well-differentiated NETs secrete the protein, regardless of location.
CgA testing is particularly useful for monitoring patients already diagnosed with a NET. Serial measurements help assess how effectively therapy is working. A significant decrease in CgA levels often corresponds to a positive response to treatment and a reduction in tumor burden.
CgA also serves as a surveillance marker for detecting disease recurrence after successful treatment. An unexpected rise in concentration can be the first biochemical indication that the tumor has returned or is progressing, sometimes appearing before changes are visible on imaging scans. Higher concentrations are typically observed in patients with more advanced or metastatic disease, as the CgA level often correlates with the size and extent of the tumor.
Understanding the Reference Range (ng/ml)
The standard unit for measuring Chromogranin A concentration in the blood is nanograms per milliliter (ng/mL). A typical reference range for a healthy adult is often cited as approximately 19 to 98 ng/mL, but this is a generalized figure.
The exact numerical range considered “normal” can vary significantly and is not universal across all laboratories. This variability is directly related to the specific testing method, or assay, utilized by the laboratory. Variations in the antibodies used in these kits can cause them to recognize different fragments of the CgA protein, leading to differing results.
It is important for patients and clinicians to always consult the specific reference range printed on the individual laboratory report to interpret the CgA concentration correctly. Sequential CgA measurements for monitoring disease should ideally be performed using the same laboratory and the same assay method to ensure meaningful comparison over time.
Interpreting Abnormal CgA Levels
When a CgA test result falls outside the established reference range, it requires careful interpretation, as the cause is not always a neuroendocrine tumor. Elevated CgA levels are the most common abnormal finding and strongly suggest the presence of a NET, especially if the concentration is significantly higher than the upper limit of normal. The higher the CgA level, the more likely it is that a substantial tumor burden exists, potentially indicating metastasis.
However, several non-tumor conditions and medications can also lead to elevated CgA levels, resulting in a false-positive result. The most common cause of non-NET elevation is the use of proton pump inhibitors (PPIs). PPIs stimulate enterochromaffin-like cells in the stomach to grow and secrete CgA, often raising levels several-fold.
Other conditions that can interfere with CgA concentration include impaired kidney function, since the protein is partially cleared by the kidneys. Chronic renal failure can cause CgA to accumulate in the bloodstream, leading to an artificially high reading. Severe chronic inflammation, chronic atrophic gastritis, and liver diseases like cirrhosis are also known to cause moderate CgA elevation.
A result below the normal range is rarely a cause for concern in an individual not previously diagnosed with a NET. Conversely, for a patient undergoing treatment, a low CgA level or a significant drop from a previously high level is a favorable sign, suggesting a positive response to therapy.