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.

Clinical significance

5-HIAA is tested by 24-hour urine samples combined with an acidic additive to maintain pH below 3. Certain foods and drugs are known to interfere with the measurement. 5-HIAA levels can vary depending on other complications, including tumors, renal malfunction, and small bowel resection.

Since 5-HIAA is a metabolite of serotonin, testing is most frequently performed for the diagnosis of carcinoid tumors of the enterochromaffin (Kultschitzsky) cells of the small intestine, which release large amounts of serotonin. Values greater than 25 mg per 24 hours (higher if the patient has malabsorption) are strong evidence for carcinoid.

Low levels of 5-HIAA in the cerebrospinal fluid have been associated with aggressive behavior and suicide by violent means, correlating with diminished serotonin levels.^[1]

Elevated serotonin (hyperserotonemia) is one of the most common biological findings in autism^[2] and 5-HIAA may be elevated in patients with autistic spectrum disorders.

Limitations

5-HIAA may be normal with nonmetastatic carcinoid tumor and may be normal even with the carcinoid syndrome, particularly in subjects without diarrhea, because some patients with the carcinoid syndrome excrete nonhydroxylated indolic acids.

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. 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 (enlarged liver), 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, and thus 5-HIAA, 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 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.

References

Further reading

• Berk, J. Edward; Bockus, Henry L. (1985). Bockus gastroenterology. Philadelphia: W.A. Saunders. ISBN 0-7216-1777-8.  - Johnson HC Jr, “Urine Tests,” Volume 1, 342-7.

• Schultz AL, “5-Hydroxyindoleacetic Acid,” Methods in Clinical Chemistry, Pesce AJ and Kaplan LA, eds, St Louis, MO: Mosby-Year Book Inc, 1987, 714-20.

• Berk, J. Edward; Bockus, Henry L. (1985). Bockus gastroenterology. Philadelphia: W.A. Saunders. ISBN 0-7216-1777-8.  - Warner RR, “Carcinoid Tumor,” Volume 3, 1874-6.

• Agranovich AL, Anderson GH, Manji M, Acker BD, Macdonald WC, Threlfall WJ (May 1991). "Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome". J Surg Oncol 47 (1): 45–52. doi:10.1002/jso.2930470111. PMID 1708841. 

• Feldman JM (May 1986). "Urinary serotonin in the diagnosis of carcinoid tumors". Clin. Chem. 32 (5): 840–4. PMID 2421946. http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=2421946.