5-Hydroxyindoleacetic acid

5-Hydroxyindoleacetic acid (5-HIAA) is the main metabolite of serotonin in the human body. In chemical analysis of urine samples, 5-HIAA is used to determine the body's levels of serotonin.

Synonyms
5-HIAA, Quantitative, 24-Hour Urine; Serotonin Metabolite, 24-Hour Urine

Test for 5-HIAA
24-hour urine volume is measured and recorded on the request form.

Specimen: Urine (24-hour)

Volume: 30 mL aliquot Minimum Volume: 1 mL aliquot

Container: Plastic urine container, no preservative (Note: 30 mL 6N HCl or 1 g/L boric acid may be added as a preservative for other tests without harm to 5-HIAA.) Collection: The patient is instructed to void at 8 AM and discard the specimen. Then collect all urine including the final specimen voided at the end of the 24-hour collection period (ie, 8 AM the next morning). Screw the lid on securely. Label container with patient's name, date, and time. Measure and record total urine volume. Mix well; send aliquot. Storage Instructions: Refrigerate at 2°C to 8°C up to 1 month.

Transport: Frozen Patient Preparation: Avoid bananas, avocados, plums, eggplant, tomatoes, plantain, pineapples, walnuts, and interfering drugs (see Interfering Substances Appendix) for a 72-hour period prior to and during the collection.

Reference Interval: 0.0-8.0 mg/24 hours

If a borderline elevation of 5-HIAA is found, sample should be recollected following withdrawal of dietary and medication sources that might elevate 5-HIAA (see Patient Preparation). Nontropical sprue may cause a slight increase in urinary 5-HIAA. 5-HIAA levels are lowered by renal insufficiency and after small bowel resection. When a patient strongly suspected for carcinoid syndrome shows normal or borderline increases of 5-HIAA, two possibilities should be considered: one, that large amounts of serotonin produced are not being metabolized, in which case blood levels of serotonin are required to document the diagnosis; and two, that secretion of 5-HIAA by the tumor is intermittent, in which case repeat timed specimen collections are needed to demonstrate the abnormality.

Use
A serotonin analysis is most frequently performed for the diagnosis of carcinoid tumors of the enterochromaffin (Kultschitzsky) cells of the small intestine. These tumor cells release large amounts of serotonin, which can produce the clinical syndrome of flushing, diarrhea, and right-sided heart failure. The most frequently used diagnostic test for carcinoid tumors is 5-HIAA, the final metabolite of serotonin. Diagnose carcinoid tumors and syndrome; values >25 mg/24 hours (higher if the patient has malabsorption) are strong evidence for carcinoid. Limitations 5-HIAA may be normal with nonmetastatic carcinoid tumor and may be normal even with the carcinoid syndrome, particularly in subjects without diarrhea. Some patients with the carcinoid syndrome excrete nonhydroxylated indolic acids, not measured as 5-HIAA.1 Midgut carcinoids are most apt to produce the carcinoid syndrome with 5-HIAA elevation. Patients with renal disease may have falsely low 5-HIAA levels in the urine.2 5-HIAA is increased in untreated patients with malabsorption, who have increased urinary tryptophan metabolites. Such patients include those with celiac disease, tropical sprue, Whipple disease, stasis syndrome, and cystic fibrosis. It is increased in those with chronic intestinal obstruction.3 Poor correlation exists between 5-HIAA level and the clinical severity of the carcinoid syndrome.3 Recent studies confirm its use as a prognostic factor in this disease.4 Methodology High-pressure liquid chromatography (HPLC) with electrochemical (EC) detection Additional Information: 5-HIAA is the major urinary metabolite of serotonin, a ubiquitous bioactive amine. Serotonin, and consequently 5-HIAA, are produced in excess by most carcinoid tumors, especially those producing the carcinoid syndrome of flushing, hepatomegaly, diarrhea, bronchospasm, and heart disease. Quantitation of urinary 5-HIAA is the best test for carcinoid, but scrupulous care must be taken that specimen collection and patient preparation have been correct. Carcinoid tumors may cause increased excretion of tryptophan, 5-hydroxytryptophan and histamine as well as serotonin. Serum serotonin assay may detect some carcinoids missed by 5-HIAA assay. The production and metabolism of serotonin is dependent upon the tissue of origin of the tumor. Tumors from midgut cells, such as ileal carcinoid usually contain and release large quantities of serotonin. These amounts may not be fully reflected in the amount of the metabolite (5-HIAA) in urine, because little is metabolized. Tumors derived from foregut cells (bronchial, pancreatic, duodenal, or biliary carcinoid) produce large amounts of serotonin, which is oxidized within the tumor to 5-HIAA. With these tumors, urinary excretion of 5-HIAA is often much higher than would be expected from clinical presentation. Tumors derived from hindgut cells (rectal carcinoid) rarely produce excess serotonin or 5-HIAA.

Of 75 patients with carcinoid tumors, 75% had above normal urinary 5-HIAA excretion and 64% had above normal serotonin excretion.5

Carcinoid tumors are enterochromaffin neoplasms containing amine precursor uptake and decarboxylation cells (APUDomas). They occur in the multiple endocrine neoplasia syndrome (MEN) I or II but are often not a part of those entities. Occasional carcinoids secrete other substances, including ACTH, gastrin, insulin, VIP, and calcitonin.