Is there a test to check serotonin levels?

Testing for Serotonin Levels

Yes, there are tests to measure serotonin levels, but direct serotonin measurement is problematic and rarely used in routine clinical practice—instead, the 24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA), serotonin's breakdown product, is the standard clinical test, particularly for diagnosing carcinoid syndrome in neuroendocrine tumors. 1

Standard Clinical Testing Approach

Primary Test: 24-Hour Urine 5-HIAA

• The 24-hour urine collection for 5-HIAA is the established clinical test for assessing serotonin production, with specificity close to 90% for detecting serotonin-secreting neuroendocrine tumors 1
• This test measures the metabolite rather than serotonin itself because reliable blood serotonin assay has been problematic and is only performed in a few specialized centers 1
• Critical dietary and medication restrictions are required for 3 days before and during collection: avoid avocados, bananas, cantaloupe, eggplant, pineapples, plums, tomatoes, hickory nuts/pecans, plantains, kiwi, dates, grapefruit, honeydew, walnuts, coffee, alcohol, and smoking 1
• Medications that interfere include acetaminophen, ephedrine, diazepam, nicotine, guaifenesin, and phenobarbital 1

Alternative Blood-Based Testing

• Platelet serotonin measurement shows very high correlation (r=0.97) with cerebrospinal fluid levels and is preferable to direct blood serotonin measurement since it is less invasive than CSF collection 2
• Direct plasma serotonin has lower correlation with CSF levels (r=0.57 in humans) and is less reliable 2
• Blood serotonin assays require specialized sample preparation including siliconized glassware/plasticware to prevent serotonin adsorption, extraction procedures, and specific platelet washing protocols 2, 3

Clinical Context and Limitations

When Testing is Indicated

• Primary indication is diagnosis of carcinoid syndrome in patients with neuroendocrine tumors, particularly those of the jejunum, ileum, proximal colon, and appendix (>70% secrete serotonin) 1
• Carcinoid syndrome presents with skin flushing of upper thorax, secretory diarrhea, and bronchoconstriction 1
• Testing helps assess treatment efficacy and changing prognosis in confirmed neuroendocrine tumors 1

Important Caveats

• Postoperative 5-HIAA may be within reference range if the tumor was resected before diagnosis, requiring additional markers like chromogranin A and neurokinin A to detect residual disease 1
• Chromogranin A is elevated in 75% of carcinoid tumors and should be measured alongside 5-HIAA as a complementary biomarker 1
• There is no validated clinical test for measuring serotonin levels to guide psychiatric treatment with selective serotonin reuptake inhibitors (SSRIs)—genetic testing for CYP450 polymorphisms measures drug metabolism, not serotonin levels 1

Research vs. Clinical Testing

• CSF serotonin measurement via HPLC with electrochemical detection is available for research purposes but requires lumbar puncture and is not used in routine clinical practice 4, 5
• Advanced methods like HPLC coupled to mass spectrometry exist for biological fluid analysis but remain primarily research tools 6

Common Pitfalls to Avoid

• Do not order serotonin testing for psychiatric conditions like depression—there is no established clinical utility, and CSF measurements are invasive research procedures 4
• Do not interpret 5-HIAA results without confirming proper dietary and medication restrictions—false positives are common without adherence to the 3-day restriction protocol 1
• Do not rely solely on 5-HIAA in postoperative patients—combine with chromogranin A and neurokinin A for comprehensive assessment of residual neuroendocrine tumor disease 1
• Contact the laboratory before collection to ensure proper handling and restriction protocols are followed 1