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
Procedure:
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.
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.
References:
1. Tellez MR, Mamikunian G, O’Dorisio TM et al. A single fasting plasma 5-HIAA value correlates with 24-hour urinary 5-HIAA values and other biomarkers in midgut neuroen
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. 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.