Serotonin Assay: Clinical Applications
Serotonin assays are primarily used for diagnosing and monitoring neuroendocrine tumors (NETs), particularly carcinoid tumors, which secrete excessive amounts of serotonin. 1
Primary Clinical Indication: Neuroendocrine Tumors
The majority of tumors of the jejunum, ileum, proximal colon, and appendix (>70%) secrete serotonin, making serotonin measurement essential for their diagnosis and follow-up. 1 Additionally, 10-35% of NETs of the stomach and respiratory system also secrete serotonin. 1
Diagnostic Utility in Three Key Areas:
- Initial diagnosis of serotonin-secreting NETs 1
- Assessment of treatment efficacy by monitoring changes in serotonin levels 1
- Prognostic assessment through serial measurements 1
Measurement Methods and Practical Considerations
Direct Serotonin Measurement
Reliable assay of serotonin in blood has been problematic but is performed in a few specialized centers. 1 Modern methods include:
- Platelet serotonin measurement may be the most sensitive marker for detecting carcinoid tumors that secrete only small amounts of serotonin 2
- Automated mass spectrometry (XLC-MS/MS) provides the most sensitive and specific quantification, with detection limits as low as 0.9 nmol/L in plasma 3
- HPLC with electrochemical or fluorometric detection has become the method of choice, combining selectivity, sensitivity, and high precision 2, 4
Alternative Marker: Urinary 5-HIAA
The breakdown product of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), may be readily measured in a 24-hour urine collection and serves as the most commonly used alternative to direct serotonin measurement. 1
Critical Pitfalls with 5-HIAA Testing:
- Contact the laboratory before collection to ensure inappropriate foods and drugs are excluded for 3 days before and during urine collection 1
- Many dietary restrictions and drug interferences affect measurement accuracy 1
- Postoperative measurements may be falsely normal if tumors were resected before diagnosis, as urinary 5-HIAA may fall within reference range after surgical removal 1
Clinical Context and Limitations
When Serotonin Assays Are Most Useful:
Platelet serotonin is particularly valuable when tumors secrete only small amounts of serotonin and/or its precursor 5-hydroxytryptophan. 2 Reference values in healthy adults are approximately 6.6 nmol/10⁹ platelets in the platelet pellet and 5.5 nmol/10⁹ platelets in platelet-rich plasma. 5
Combined Marker Strategy:
For patients with suspected residual disease after surgery, measuring chromogranin A and neurokinin A together with 5-HIAA will indicate residual disease in more than 90% of patients. 1 This combined approach is essential because:
- Surgical cure is rare 1
- All patients except those with some small appendiceal tumors should be followed indefinitely 1
- Single markers may miss disease in postoperative settings 1
Emerging Applications
Beyond neuroendocrine tumors, serotonin measurement has emerging roles in:
- Psychiatric disorders: Correlations exist between serum serotonin levels and anxiety/depression, particularly in patients with comorbid conditions like type 2 diabetes 6
- Physiological research: Serotonin is implicated in liver cell regeneration and bone formation 3
The key advantage of modern mass spectrometry methods is their ability to accurately quantify serotonin for both routine diagnostic procedures and research in serotonin-related disorders, overcoming limitations of conventional HPLC. 3