What lab tests are used to diagnose carcinoid syndrome?

Laboratory Tests for Diagnosing Carcinoid Syndrome

The primary laboratory tests for diagnosing carcinoid syndrome are 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) and serum chromogranin A (CgA), which should be ordered as baseline tests in all patients with suspected carcinoid syndrome. 1, 2

First-Line Laboratory Tests

1. 24-Hour Urinary 5-HIAA

• Gold standard biochemical marker for carcinoid syndrome
• Particularly useful for midgut carcinoids (70% of patients show elevated levels) 1
• Sometimes elevated in foregut carcinoids
• Not typically elevated in hindgut carcinoids 1
• Collection requirements:
  • Requires proper 24-hour collection with preservative
  • Patient must avoid certain foods and medications 24 hours before and during collection:
    • Foods to avoid: banana, avocado, aubergine, pineapple, plums, walnuts (can cause false positives) 1
    • Medications to avoid: paracetamol, fluorouracil, methysergide, naproxen, caffeine (false positives) 1
    • Medications causing false negatives: levodopa, aspirin, ACTH, methyldopa, phenothiazines 1

2. Serum Chromogranin A (CgA)

• General marker for all neuroendocrine tumors
• Elevated in most carcinoid cases, particularly with metastatic disease 1, 2
• Not specific to carcinoid syndrome but highly sensitive
• Blood collection requires a 10 ml standard heparin bottle with trasylol (aprotinin 0.2 ml, 2000 KIU) 1
• Must be spun immediately before freezing 1

Additional Specific Tests Based on Tumor Location

For Midgut Carcinoids:

• Tachykinins (neurokinin A and B) - typically elevated 1, 2

For Foregut Carcinoids:

• 24-hour urinary 5-HIAA (may be only moderately elevated) 1
• Serum CgA (often elevated) 1

For Hindgut Carcinoids:

• General markers like CgA (5-HIAA typically not elevated) 1

Alternative Testing Options

Plasma/Serum 5-HIAA

• Emerging alternative to 24-hour urine collection
• Similar diagnostic sensitivity and specificity to urinary 5-HIAA 3
• More convenient than 24-hour urine collection 4
• At a cut-off value of 118 nmol/L, plasma 5-HIAA shows:
  • Sensitivity: 89%
  • Specificity: 97%
  • Test efficiency: 93% 4
• Important consideration: Renal function affects serum/plasma 5-HIAA levels
  • Levels increase when eGFR falls below 60 mL/min/1.73 m² 3

Whole Blood Serotonin

• Can be useful as a complementary test
• More sensitive than urinary 5-HIAA for detecting carcinoids that secrete small amounts of serotonin 5
• Limitations:
  • Saturates in platelets at 40 nmol/10⁹ platelets
  • Less suitable for monitoring treatment response 4

Testing Algorithm

1. Initial Screening:

   • Order both 24-hour urinary 5-HIAA and serum CgA 1, 2
   • Consider plasma/serum 5-HIAA as an alternative if 24-hour collection is problematic 3, 4

2. Based on suspected tumor location:

   • Midgut: Focus on 24-hour urinary 5-HIAA (usually elevated) and tachykinins 1
   • Foregut: Check 24-hour urinary 5-HIAA (may be only moderately elevated) 1
   • Hindgut: Rely more on CgA as 5-HIAA is typically not elevated 1

3. If initial tests are negative but clinical suspicion remains high:

   • Consider whole blood/platelet serotonin measurement 5
   • Order a complete gut hormone panel including: gastrin, glucagon, somatostatin, pancreatic polypeptide, vasointestinal peptide, and neurotensin 1

Important Caveats

• Pre-analytical factors: Patient preparation is critical for accurate 5-HIAA measurement

  • Dietary and medication restrictions must be strictly followed 1, 2
  • Improper collection or handling can lead to false results

• Interpretation challenges:

  • A positive biochemical test with liver metastases and symptoms is highly suggestive of carcinoid, but histological confirmation is usually necessary 1
  • Renal impairment can cause elevated serum/plasma 5-HIAA levels unrelated to carcinoid 3

• Laboratory methodology:

  • Modern techniques like HPLC-MS/MS offer improved sensitivity and specificity 6, 7
  • Reference ranges may vary between laboratories and methods

Remember that while laboratory tests are essential for diagnosis, definitive diagnosis requires histological confirmation whenever possible 1, 2.