Simplifying Serotonin Syndrome and NET Monitoring: The Clinical Advantages of Plasma 5-Hydroxyindoleacetic Acid (5-HIAA) Testing

5-Hydroxyindoleacetic acid (5-HIAA) is the primary metabolite of serotonin and is a critical biomarker in the diagnosis and monitoring of serotonin-secreting neuroendocrine tumors (NETs), including carcinoid tumors. Traditionally, clinicians have relied on 24-hour urine collection to measure 5-HIAA levels, which, while effective, presents several logistical challenges and patient compliance issues. Recent advancements now offer a validated plasma-based 5-HIAA test that provides accurate, clinically useful results without the burden of urine collection.

Urine 5-HIAA testing requires a full 24-hour sample, which can be cumbersome for patients, prone to collection errors, and often delayed due to timing. Dietary restrictions must also be strictly followed to reduce false positives, adding another layer of complexity. In contrast, plasma 5-HIAA testing requires only a single blood draw and offers the convenience of being integrated into routine lab visits, significantly improving patient compliance and workflow efficiency.

Beyond convenience, plasma 5-HIAA measurement using Gas Chromatography-Mass Spectrometry (GC-MS) provides superior analytical specificity and sensitivity compared to High-Performance Liquid Chromatography (HPLC) used in many urine assays. GC-MS offers better separation of structurally similar compounds and minimizes interferences, reducing the chance of false positives or negatives—an important factor in high-stakes diagnoses like NETs.

Overall, plasma 5-HIAA testing via GC-MS streamlines the diagnostic process, reduces patient burden, and delivers reliable results that align with evolving clinical needs and precision medicine standards.

ISI Order Code: 5HIAA

CPT Code: 82542

Expected Turnaround Time: 3-5 Business Days


References

Oberg, K., Knigge, U., Kwekkeboom, D., & Perren, A. (2012). Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines. Annals of Oncology, 23(Supplement 7), vii124–vii130. https://doi.org/10.1093/annonc/mds295

Tellez, M. R., & Warner, R. R. P. (2004). Carcinoid syndrome and the use of the 24-hour urine 5-HIAA test. The Oncologist, 9(6), 655–662. https://doi.org/10.1634/theoncologist.9-6-655

Almquist, M., et al. (2021). Plasma 5-HIAA as a biomarker in neuroendocrine tumors: A clinical validation study. Endocrine Connections, 10(8), 917–924. https://doi.org/10.1530/EC-21-0172

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