5-Hydroxyindoleacetic acid (5-HIAA)

What is being analysed?
The test measures the concentration of 5-hydroxyindoleacetic acid in the urine. 5-hydroxyindoleacetic acid is a muscle stimulant and the main metabolite of serotonin, a hormone derived from tryptophan. Serotonin is produced by the nervous system, mainly the brain, but also by particular cells in the bronchial tree (lungs) and the gastrointestinal tract. It is a neurotransmitter and a vasoconstrictor, contributes to the sleep-wake cycle and affects mood. It is metabolised in the liver and its metabolites, including 5-hydroxyindoleacetic acid, are excreted in the urine.

Normally only small amounts of 5-hydroxyindoleacetic acid are present in the urine. Large amounts of serotonin and 5-hydroxyindoleacetic acid can, however, be produced by carcinoid tumours. These are slow-growing tumours that affect the gastrointestinal tract, the appendix and the lungs. According to the American Cancer Society, about 5,000 carcinoids are diagnosed each year in the United States. The number could be higher, but most are small and cause no symptoms. Carcinoids found in patients without symptoms during surgery performed for other reasons are called “incidental” tumours. A small percentage of these tumours can grow large enough to cause bowel or bronchial obstruction.

About 10% of carcinoids, mainly those of the gastrointestinal tract, produce enough serotonin to cause symptoms such as flushing, diarrhoea, a fast heart rate and asthma, usually only after they have spread to the liver. These symptoms are known as carcinoid syndrome. The serotonin that causes carcinoid syndrome can be released continuously or intermittently and can lead to significant amounts of 5-hydroxyindoleacetic acid in the urine.

How is the sample collected for testing?
All the urine passed over 24 hours must be collected, avoiding direct exposure to sunlight to prevent spontaneous oxidation, acidified with HCl and refrigerated.

Is any preparation needed to ensure the quality of the sample?
Preparation before sampling is important for an accurate 5-HIAA result. Foods such as avocados, bananas, pineapples, plums, almonds, tomatoes, kiwis and aubergines can interfere with the 5-HIAA measurement and should therefore be avoided for 3 days before and during the urine collection. A number of medicines can affect the test, but you should talk to your doctor before reducing or stopping any treatment.

How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?

How is it used?
5-hydroxyindoleacetic acid may be requested on its own or together with blood serotonin to help diagnose and follow carcinoid tumours over time. The metabolite is preferably measured in a 24-hour urine collection because 5-hydroxyindoleacetic acid levels can vary during the day. Sometimes, when a 24-hour collection is not possible, a random urine sample corrected for urinary creatinine is used. This type of sample, however, does not give an accurate measurement, because it may miss a high level of 5-hydroxyindoleacetic acid if release is intermittent.

When is it requested?
This test is requested mainly when there are symptoms suggestive of a carcinoid. Once a serotonin-secreting carcinoid has been diagnosed, the test is repeated at regular intervals to assess how well treatment is working.

What does the test result mean?
Significantly raised levels of 5-hydroxyindoleacetic acid in a 24-hour urine collection in people with symptoms of carcinoid syndrome are suggestive of, but not diagnostic for, a carcinoid tumour. A definitive diagnosis requires the tumour to be located and examined histologically. For this reason imaging tests may be requested.

A patient with symptoms could have a carcinoid tumour even with normal 5-hydroxyindoleacetic acid levels: the tumour may not secrete serotonin, or it may secrete it intermittently. A serotonin-secreting carcinoid tumour is unlikely in the absence of symptoms and with 5-hydroxyindoleacetic acid levels within the reference range.

When monitoring patients with a carcinoid undergoing treatment, falling 5-hydroxyindoleacetic acid levels indicate a response to treatment, while rising or persistently high levels indicate a poor response.

Is there anything else I should know?
Many medicines can alter the measurement of 5-hydroxyindoleacetic acid. Medicines that increase it include paracetamol, caffeine, ephedrine, diazepam (Valium), nicotine, glyceryl guaiacolate (found in some cough remedies) and phenobarbital. Medicines that can reduce it include aspirin, ethyl alcohol, imipramine, levodopa, MAO inhibitors, heparin, isoniazid, methyldopa and tricyclic antidepressants. You should seek medical advice before reducing or stopping any treatment.

1. Are there other serotonin metabolites?
2. Can the urine 5-hydroxyindoleacetic acid test be done at home?
3. Will I get accurate results if I continue my medication?
4. Are some people at greater risk of developing a carcinoid tumour?

1. Are there other serotonin metabolites?
Yes, the other main metabolite is 5-hydroxytryptophol (5-HTOL). It is not measured in routine tests but can sometimes be measured in relation to 5-hydroxyindoleacetic acid to assess alcohol intake. An increased 5-HTOL/5-HIAA ratio can indicate alcohol consumption, both in living people and post mortem.

2. Can the urine 5-hydroxyindoleacetic acid test be done at home?
No, this test requires specialised equipment and must be carried out in a laboratory. Not all laboratories perform it; in some cases the sample is sent to a reference laboratory.

3. Will I get accurate results if I continue my medication?
If your medicine is one of those that change serotonin and 5-HIAA levels, the results may be affected. However, you need medical advice before stopping treatment before and during the sample collection. If treatment must continue, the results will be interpreted with this in mind.

4. Are some people at greater risk of developing a carcinoid tumour?
Anyone of any age can develop a carcinoid tumour, but according to the American Cancer Society the average age at diagnosis is usually between 55 and 65. A family history of multiple endocrine neoplasia (MEN 1), a genetic condition that increases the risk of tumours of the endocrine system, may increase the risk of developing a carcinoid.