5-HIAA (5-Hydroxyindoleacetic acid), Plasma (*Collected with EDTA plasma or ISI’s Z-tubeTM) NYS DOH Approved tests PFI#9065

Clinical Significance:
Functioning neuroendocrine tumors (NETs) can secrete a wide variety of peptides and hormones. More specifically, patients with midgut NETs have elevated levels of serotonin and its degradation product, 5-hydroxyindoleacetic acid (5-HIAA). Urine 5-HIAA measurement has long been the standard test for the diagnosis of midgut and foregut NETs. Since our publication in 2012 offering the first clinically available plasma 5-HIAA assay, several publications showed that plasma levels correlate well with the 24-hour urinary 5-HIAA assays. This test has been clinically validated for NETS patients who previously relied on the 24-hour urinary 5-HIAA. The plasma 5-HIAA saves time, alleviates the need to collect urine in a container for 24 hours, and provides equivalent clinical information. The ISI plasma 5-HIAA test is NY approved and has been utilized in several ongoing clinical trials.

Reference Range:
Up to 22 ng/mL

5-HIAA plasma is measured by GC-MS/MS.

Patient Preparation:
Patient should fast overnight prior to collection of specimen.

Specimen Collection:
Collect using EDTA “purple top” plasma tube OR 10mL blood directly into ISI’s Z-tubeTM Preservative, and separate as soon as possible. Freeze plasma immediately after separation. Special Z-tubeTM Preservatives are available from ISI. Minimum specimen size is 0.5mL. 

Note: One Z-tubeTM may be shared for up to three tests: Pancreastatin, Neurokinin A, and 5HIAA. This profile has been shown to assist physicians with prognosis. After centrifuging the tube, aliquot 1mL per test in separate vials, mark with name of test and freeze.

Important Precaution:
Specimens for this assay must be collected using EDTA “purple top” or ISI’s Z-tubeTM . Specimens must be shipped frozen; specimens are not stable refrigerated or ambient. No substitute preservatives are acceptable.

Special Specimens:
*Frozen EDTA or Z-tube plasma are acceptable sample types for this assay.

Shipping Instructions:
Ship specimens frozen in dry ice.


1. Tellez MR, Mamikunian G, O’Dorisio TM, Vinik AI, Woltering EA. A single fasting plasma 5-HIAA value correlates with 24-hour urinary 5-HIAA values and other biomarkers in midgut neuroendocrine tumors (NETs). Pancreas. 2013 Apr;42(3):405-10. doi: 10.1097/MPA.0b013e318271c0d5. PMID: 23160483.

2. Wedin M, Mehta S, Angerås-Kraftling J, Wallin G, Daskalakis K. The Role of Serum 5-HIAA as a Predictor of Progression and an Alternative to 24-h Urine 5-HIAA in Well-Differentiated Neuroendocrine Neoplasms. Biology (Basel). 2021 Jan 21;10(2):76. doi: 10.3390/biology10020076. PMID: 33494283; PMCID: PMC7909826

3. Woltering EA, Voros BA, Thiagarajan R, Beyer DT, Ramirez RA, Wang YZ, Mamikunian G, Boudreaux JP. Plasma Neurokinin A Levels Predict Survival in Well-Differentiated Neuroendocrine Tumors of the Small Bowel. Pancreas. 2018 Aug;47(7):843-848. doi: 10.1097/MPA.0000000000001092. PMID: 29939909.4.

4. Cai H-L, Zhu R-H, Li H-D, et al. MultiSimplex optimization of chromatographic separation and dansyl derivatization conditions in the ultra performance liquid chromatography-tandem mass spectrometry analysis of neurotransmitters in human urine. J Chromato B 2011;879:1993-1999.
5. Gonzalez RR, Fernandez RF, Vidal JLM et al. Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of neurotransmitters in rat brain samples. J Neuro Meth 2011;198: 187-194.
6. Stephanson N, Helander A, Beck O. Alcohol biomarker analysis: simultaneous determination of 5-hydroxytryptophol glucuronide and 5-hydroxyindoleacetic acid by direct injection of urine using ultra-performance liquid chromatographytandem mass spectrometry. J Mass Spect 2007;42: 940-949.