What is chromogranin A?

Chromogranin A (CgA): A Biomarker for Neuroendocrine Tumors

Chromogranin A (CgA) is a secretory protein found in dense-core vesicles of neuroendocrine cells that serves as the most valuable biomarker for diagnosing, monitoring, and determining prognosis in patients with neuroendocrine tumors (NETs), with moderate sensitivity (49-67%) but good specificity (78%) that improves significantly for larger tumors. 1

Characteristics and Clinical Utility

• CgA is a member of the granin family of secretory proteins present in the dense-core vesicles of neuroendocrine cells
• It is co-released with peptide hormones during secretion, making it a reliable marker of neuroendocrine activity
• CgA is elevated in 60% or more of patients with either functioning or non-functioning pancreatic NETs 2, 1
• CgA serves as an excellent immunohistochemical marker for neoplasms of neuroendocrine origin

Diagnostic Value

CgA elevation varies significantly by tumor type:

• Gastrinomas: 100% elevation
• Pheochromocytomas: 89% elevation
• Carcinoid tumors: 80% elevation
• Non-functioning pancreatic NETs: 69% elevation
• Medullary thyroid carcinomas: 50% elevation 1, 3

The sensitivity of CgA ranges from 49-67% with specificity of 77-78% for detecting NETs. Importantly, CgA levels correlate strongly with tumor burden, meaning small tumors may go undetected. 1, 3

Prognostic Value

CgA has significant prognostic value:

• CgA levels elevated twice the normal limit or higher are associated with shorter survival times for patients with metastatic NETs (HR 2.8,95% CI 1.9-4.0, P<0.001) 1
• CgA levels appear to be prognostic in patients treated with everolimus 2, 1

Monitoring and Follow-up

For patients with confirmed NETs:

• CgA should be checked every 3-6 months if elevated at baseline 1
• CgA should be used as a baseline measurement before treatment
• CgA should be monitored during treatment to assess response
• CgA should be tracked during surveillance to detect recurrence 1

Important Limitations and False Positives

Several conditions can cause falsely elevated CgA levels:

• Proton pump inhibitor (PPI) use (PPIs should be discontinued for at least 1 week before CgA measurement)
• Renal or hepatic failure
• Hypertension
• Chronic gastritis 2, 1

Clinical Applications

CgA is particularly valuable in:

1. Detecting "non-functioning" neuroendocrine tumors for which no specific hormonal marker exists
2. Monitoring carcinoids and pheochromocytomas as a more stable marker than serotonin and catecholamines
3. Following disease progression and treatment response in patients with NETs
4. Providing prognostic information in patients with metastatic disease

Comprehensive NET Evaluation

For comprehensive NET evaluation, CgA should be combined with:

• Specific hormonal markers based on suspected syndrome
• 24-hour urinary 5-HIAA for carcinoid syndrome
• Appropriate imaging (multiphasic CT/MRI, somatostatin receptor imaging) 1

While CgA is the best general neuroendocrine serum marker available, it should be interpreted in the clinical context and alongside other diagnostic modalities, as its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors. 3