5-Hydroxyindoleacetic acid

Test/Range/Collection

5 -Hydroxyindoleacetic acid, urine (5-HIAA)

0–8 mg/24 hr [0–40 mcmol/d]

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Collect 24-hr or random urine, and refrigerate.

Patients should abstain from medications that may affect metabolism of serotonin and avoid foods that are rich in serotonin (eg, avocados, bananas, pineapple, eggplant) for at least 72 hrs before and during urine collection.

Physiologic Basis

Serotonin (5-hydroxytryptamine) is a neurotransmitter that is metabolized by monoamine oxidase (MAO) to 5-HIAA and then excreted into the urine.

Intestinal carcinoid tumors along with neuroendocrine tumors can produce excess amounts of serotonin and 5-HIAA, especially in individuals with carcinoid syndrome. Biochemical diagnosis of gastrointestinal carcinoids is established by demonstrating elevation of urinary 5-HIAA or plasma serotonin or chromogranin A.

Interpretation

Increased in: Metastatic carcinoid tumor (foregut, midgut, and bronchial). Nontropical sprue (slight increase). Diet: Bananas, walnuts, avocado, eggplant, pineapple, plums. Drugs: reserpine.

Negative in: Rectal carcinoids (usually), renal insufficiency. Drugs: MAO inhibitors, phenothiazines.

Test is often falsely positive if pretest probability is low. Using 5-HIAA/Cr ratio may improve performance, especially if the urine collection is random or other than 24-hr.

Comments

Urinary 5-HIAA excretion is used as a biochemical tumor marker for clinical diagnosis, to monitor treatment effects, and as a prognostic predictor. A very high concentration of urinary 5-HIAA is an indicator that a gastrointestinal carcinoid tumor is malignant.

Because most carcinoid tumors drain into the portal vein and serotonin is rapidly cleared by the liver, the carcinoid syndrome (flushing, bronchial constriction, diarrhea, hypotension, and cardiac valvular lesions) associated with secretion of serotonin and other vasoactive substances is a late manifestation of carcinoid tumors, appearing only after hepatic metastasis has occurred.

Bolanowski M et al. Neuroendocrine neoplasms of the small intestine and the appendix—management guidelines. Endokrynol Pol 2013;64:480.  [PMID: 24431119]

Kunz PL et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas 2013;42:557.  [PMID: 23591432]

Strosberg J. Neuroendocrine tumours of the small intestine. Best Pract Res Clin Gastroenterol 2012;26:755.  [PMID: 23582917]