Carcinoid Tumor Markers
For diagnosing carcinoid tumors, measure baseline chromogranin A (CgA) and 24-hour urinary 5-HIAA in all suspected cases, as these are the recommended first-line markers. 1
Primary Diagnostic Markers
Chromogranin A (CgA)
- CgA is the single most important general marker for all neuroendocrine tumors, including carcinoids, with elevated levels in 99% of patients with carcinoid tumors. 2
- CgA should be measured in plasma/serum as the primary screening marker regardless of whether the tumor is functioning or non-functioning. 1, 3
- CgA is particularly useful for gastric carcinoids with metastases and serves three critical functions: assists initial diagnosis, monitors treatment response, and provides prognostic information. 1
- Elevated CgA levels (twice the normal limit or higher) correlate with tumor burden and are associated with shorter survival times (HR 2.8,95% CI 1.9-4.0). 4, 5
24-Hour Urinary 5-HIAA
- 5-HIAA is the gold standard for diagnosing carcinoid syndrome with approximately 90% specificity and 73% sensitivity. 3, 4
- For midgut carcinoids, urinary 5-HIAA is elevated in 70% of patients. 1, 3
- For foregut carcinoids, urinary 5-HIAA is only sometimes raised, making CgA more reliable. 1, 3
- For hindgut carcinoids, urinary 5-HIAA is typically not elevated; rely on CgA instead. 1, 3
Location-Specific Testing Algorithm
Midgut carcinoids: Measure both CgA and 24-hour urinary 5-HIAA, as 5-HIAA sensitivity reaches 70% for this location. 1, 3
Foregut carcinoids: Prioritize CgA over 5-HIAA, as 5-HIAA is only occasionally elevated. 1, 3
Hindgut carcinoids: Use CgA exclusively, as 5-HIAA is not raised in these tumors. 1, 3
Additional Markers to Consider
- Pancreatic polypeptide: Elevated in 50% of carcinoid tumors and 80% of pancreatic neuroendocrine tumors. 1
- Tachykinins (neurokinin A and B): Raised in midgut carcinoids. 1
- Chromogranin B: May be elevated when chromogranin A is in the reference range, making it a useful complementary marker. 5
- Pancreastatin: Specifically elevated in metastatic neuroendocrine tumors (46% of patients) and not affected by conditions that falsely elevate CgA. 5, 2
Critical Pre-Collection Requirements for 5-HIAA
Dietary restrictions for 48 hours before and during collection: Avoid bananas, avocados, aubergines (eggplant), pineapples, plums, walnuts, tomatoes, paracetamol (acetaminophen), coffee, and alcohol. 1, 3, 4
Medications causing false positives: Paracetamol, fluorouracil, methysergide, naproxen, caffeine, ephedrine, and phenobarbital. 1, 3
Medications causing false negatives: Levodopa, aspirin, ACTH, methyldopa, and phenothiazines. 1
Common Pitfalls with Chromogranin A
CgA can be falsely elevated in multiple non-tumor conditions: 3, 5, 6
- Proton pump inhibitor use (most common cause)
- Renal insufficiency or dialysis
- Hepatic insufficiency
- Atrophic gastritis
- Hypertension
Before interpreting elevated CgA, confirm the patient is not taking PPIs and does not have renal failure, liver failure, hypertension, or chronic gastritis. 4
Diagnostic Performance Comparison
Chromogranin A demonstrates superior overall diagnostic utility: Sensitivity 80.6% with specificity 98.5% across all neuroendocrine tumors. 7
5-HIAA has limited sensitivity (35.1%) for general NET detection but reaches 72.5% sensitivity specifically for carcinoid syndrome. 3, 7
Combined testing with CgA plus 5-HIAA provides optimal diagnostic accuracy and should be performed together rather than sequentially. 3, 8
Monitoring Treatment Response
- Decreasing CgA and 5-HIAA levels indicate successful treatment; increasing levels suggest treatment failure. 3
- However, rising CgA levels in an asymptomatic patient with stable imaging does not necessarily mandate new therapy. 4, 5
- Measure CgA every 3-6 months during follow-up for treated carcinoid tumors. 1
Additional Baseline Tests
Other markers that may be appropriate depending on clinical presentation: Thyroid function tests (TFTs), parathyroid hormone (PTH), calcium, calcitonin, prolactin, alpha-fetoprotein, CEA, and beta-HCG. 1