From the Guidelines
Chromogranin A (CgA) is a valuable biomarker for diagnosing and monitoring gastrinomas, and elevated CgA levels are present in approximately 80-90% of patients with gastrinomas, making it a useful screening and surveillance tool. When evaluating a patient with suspected gastrinoma, I recommend obtaining a baseline CgA level along with fasting serum gastrin measurements, as both gastrin and CgA are raised in gastrinoma 1. Normal CgA levels are typically below 100 ng/mL, though reference ranges vary by laboratory. For accurate results, patients should discontinue proton pump inhibitors (PPIs) for at least 2 weeks before testing, as these medications can falsely elevate CgA levels 1. Other factors that can increase CgA include renal insufficiency, heart failure, inflammatory conditions, and certain medications.
Key Considerations
- CgA levels correlate with tumor burden, making them particularly useful for tracking disease status over time 1
- Rising CgA levels may indicate tumor progression or recurrence, even before clinical symptoms appear
- CgA is not specific for gastrinomas, so results should always be interpreted alongside other clinical findings and imaging studies
- The majority of gastrinomas are located in the duodenum rather than in the pancreas, and all patients with gastrinoma should be considered as candidates for MEN1 syndrome 1
Diagnostic Approach
- Obtain a baseline CgA level along with fasting serum gastrin measurements
- Discontinue PPIs for at least 2 weeks before testing
- Consider upper gastrointestinal endoscopy and gastric biopsy to differentiate gastrinoma from atrophic gastritis
- Secretin stimulation and intragastric pH may also be needed in some cases 1
Monitoring and Follow-up
- CgA monitoring should continue every 3-6 months to assess treatment response and detect recurrence
- Rising CgA levels may indicate tumor progression or recurrence, and should prompt further evaluation and management 1
From the Research
Relationship between Chromogranin A (CgA) levels and Gastrinoma
- The relationship between CgA levels and gastrinoma is complex, with studies suggesting that CgA measurements may not be valid in diagnosis or control of gastrinomas 2.
- Data available indicate that well-defined assays for gastrin have significantly higher diagnostic sensitivity than CgA measurements in gastrinomas 3.
- However, CgA-quantitation using processing-independent analysis (PIA) may provide an equally high diagnostic sensitivity and offer a simple possibility for estimation of the tumor-burden 3.
- Assays measuring α-amidated gastrins have high diagnostic value, except for singular patients in whom only progastrin was elevated 2.
- CgA results differed, with 11 patients having normal CgA concentrations, while all total CgA concentrations were elevated but correlated only moderately to gastrin 2.
Factors Affecting CgA Levels
- CgA levels can be affected by various factors, including age, creatinine levels, and the severity of hypertension 4.
- Short-term treatment with low dosages of the proton-pump inhibitor omeprazole can increase CgA levels, which may lead to false positive values 4.
- The increase in CgA levels is more pronounced when the baseline CgA levels are already increased by slight renal insufficiency or severe hypertension 4.
Clinical Utility of CgA in Diagnosing and Monitoring GEP-NENs
- Plasma CgA is the most widely used biochemical biomarker in the diagnostic workup and follow-up of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 5.
- CgA values were above the upper reference limit in 82% of patients at diagnosis, and median CgA levels were significantly higher in functioning than in nonfunctioning tumors 5.
- Baseline CgA levels were significantly associated with Ki-67 index and TNM stage, independently of age, sex, and primary site of the tumor 5.
- A low Ki-67 index, the type of treatment, and an early CgA decrease after treatment were positively correlated with the survival rate 5.