24-Hour Urine 5-HIAA Test: A Diagnostic Tool for Neuroendocrine Tumors
The 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA) test is a biochemical test that measures the main metabolite of serotonin in urine, primarily used to diagnose and monitor neuroendocrine tumors (NETs), particularly those causing carcinoid syndrome. 1, 2
What is 5-HIAA?
- 5-HIAA is the primary urinary metabolite of serotonin
- Serotonin is a neurotransmitter produced in excess by certain neuroendocrine tumors, especially those arising from the small intestine, appendix, and bronchial system 1
- When NETs secrete excessive serotonin, elevated levels of 5-HIAA appear in the urine
Clinical Applications
- Primary diagnostic use: Detection of carcinoid syndrome associated with NETs 1
- Monitoring purposes: Following disease progression and treatment response 1
- Prognostic value: Higher levels correlate with increased risk of carcinoid heart disease and poorer outcomes 3
Test Specifications
Collection Process
- Requires collection of all urine over a 24-hour period
- Patient must use a special container with preservative
- Complete collection is essential for accurate results
- Overnight (8-hour) collections may be considered as an alternative in some cases 4
Interpretation
- Sensitivity: Up to 100% for carcinoid syndrome
- Specificity: 85-90% for carcinoid syndrome 3
- Normal values vary by laboratory but are typically <6-10 mg/24 hours
Factors Affecting Results
Foods to avoid 48 hours before and during collection 1:
- Avocados, bananas, cantaloupe, eggplant, pineapples
- Plums, tomatoes, hickory nuts/pecans, plantains, kiwi
- Dates, grapefruit, honeydew, walnuts
Medications to avoid 1:
- Acetaminophen, ephedrine, diazepam
- Nicotine, guaifenesin (cough medicines)
- Phenobarbital, levodopa, aspirin
- Methyldopa, phenothiazines
Other recommendations:
- Avoid coffee, alcohol, and smoking for 48 hours before and during collection 1
- Consult with the laboratory about specific restrictions
Clinical Context
Diagnostic Value
- Particularly useful for midgut NETs (jejunum, ileum, appendix, proximal colon) where 70% of patients have elevated levels 1
- Sometimes elevated in foregut NETs (bronchial, gastric, pancreatic)
- Rarely elevated in hindgut NETs (distal colon, rectum) 1
Limitations
- False positives from dietary and medication interference
- False negatives can occur with certain medications
- May be normal in patients with small tumor burden or non-secreting NETs
- Recent research suggests serum 5-HIAA may be an alternative with similar diagnostic accuracy 5
Integration with Other Diagnostic Tools
For comprehensive NET evaluation, 5-HIAA should be combined with:
- Chromogranin A (general NET marker) 1, 2
- Specific hormone panels based on suspected functionality
- Imaging studies (CT, MRI, somatostatin receptor imaging) 2
- Histopathological confirmation when possible
Monitoring Applications
- Regular 5-HIAA measurements help assess treatment response
- Decreasing levels indicate successful treatment
- Increasing levels suggest disease progression or recurrence 1
- Recommended monitoring frequency: Every 3-6 months during treatment and follow-up 2
The 24-hour urine 5-HIAA test remains a cornerstone in the diagnosis and monitoring of NETs, particularly those associated with carcinoid syndrome, despite the emergence of newer biomarkers and imaging techniques.