Chromogranin A (CgA) is a protein secreted by neuroendocrine cells, which are specialized cells that possess characteristics of both nerve cells and hormone-producing endocrine cells. These cells are distributed widely throughout the body, particularly in the gastrointestinal tract, pancreas, and lungs. Measuring the concentration of CgA in the bloodstream serves as a biochemical indicator of neuroendocrine cell activity. When the CgA level is significantly elevated, it suggests an increased output from this cell system, signaling the possibility of an underlying health issue requiring immediate clinical evaluation.
Interpreting High CgA Results
A Chromogranin A level exceeding 300 picograms per milliliter (pg/mL) is considered a substantially elevated result that demands prompt attention from a healthcare provider. The normal reference range for CgA typically falls below 90 or 100 pg/mL, though the exact cutoff can vary depending on the laboratory and the specific testing method used. A result over 300 is far outside the expected range and indicates a high level of protein secretion.
This marked elevation suggests a substantial increase in the body’s neuroendocrine cell mass or activity. In the context of potential disease, the CgA number often correlates with the overall volume of the abnormal neuroendocrine tissue present. However, the number itself is not a diagnosis, and its interpretation must be done alongside a patient’s complete medical history and physical examination. A definitive medical conclusion cannot be reached based on this single blood test.
The Link to Neuroendocrine Tumors
The most serious and specific reason for a CgA level over 300 is the presence of a Neuroendocrine Tumor (NET). NETs are slow-growing, often malignant, tumors that arise from neuroendocrine cells found in organs like the pancreas, small intestine, and lungs. Because these tumors produce CgA, they often secrete large amounts of the protein into the bloodstream, making CgA a widely used tumor marker.
A CgA level significantly above the normal range, such as 300 pg/mL or higher, strongly suggests the active proliferation of these tumor cells. Studies have shown a clear relationship between the degree of CgA elevation and the extent of the disease, including tumor size and stage. Patients with metastatic NETs—where the cancer has spread to distant organs like the liver—frequently exhibit the highest CgA levels, sometimes reaching into the thousands. The CgA measurement provides an indirect assessment of the total tumor burden within the body.
The use of CgA is especially relevant for gastroenteropancreatic NETs, which are the most common type of neuroendocrine tumor. While CgA is a general marker for this class of disease, its high value helps guide clinical suspicion toward an active and potentially spreading neuroendocrine malignancy. Monitoring the CgA level over time is also useful for tracking the effectiveness of treatment, as a falling level may indicate a positive response to therapy.
Non-Tumor Causes of CgA Elevation
An elevated CgA result is not always indicative of cancer, as several non-malignant conditions can cause a false positive reading. The most frequent cause of CgA elevation is the use of certain acid-reducing medications called Proton Pump Inhibitors (PPIs). These drugs, such as omeprazole or pantoprazole, reduce stomach acid production, which triggers a compensatory biological response.
The reduction in stomach acidity leads to an increase in the hormone gastrin, which then stimulates specialized neuroendocrine cells in the stomach lining called enterochromaffin-like cells. This stimulation causes these cells to multiply and release more CgA, resulting in a spurious elevation. PPI-induced increases can be two to four times the upper limit of normal, and in some cases, can push the CgA level well over 300 pg/mL.
Other non-malignant medical conditions can also contribute to an elevated CgA level. Impaired clearance of the protein from the body due to severe kidney failure or chronic liver disease can lead to higher circulating concentrations. Furthermore, certain inflammatory conditions like chronic gastritis, inflammatory bowel disease, and severe stress or heart failure have been documented to cause CgA elevations. These possibilities must be systematically excluded before attributing the high CgA level to a neuroendocrine tumor.
Diagnostic Follow-Up After High CgA
The first step in investigating a CgA level over 300 is a careful review of the patient’s medication list, especially for PPIs. If the patient is taking an acid-reducing medication, the physician will typically recommend stopping the drug for at least two weeks before retesting the CgA level. If the level returns to the normal range after this washout period, the initial elevation is considered artifactual and is not related to a tumor.
If the CgA level remains high after addressing non-tumor causes, the focus shifts to locating the source of the protein overproduction. This diagnostic process relies heavily on specialized imaging techniques designed to visualize neuroendocrine tissue. Common anatomical scans, such as computed tomography (CT) or magnetic resonance imaging (MRI), are used to search for masses in the abdomen and chest.
More specific functional scans, such as Gallium-68 DOTATATE Positron Emission Tomography (PET) or Octreotide scans, are often employed because they utilize tracers that bind directly to receptors found on the surface of most neuroendocrine cells. These scans are highly sensitive and can pinpoint the exact location of a small or metastatic tumor. A specialist, such as an oncologist or endocrinologist, is necessary to accurately interpret these results and develop a comprehensive management strategy.