5-Hydroxyindoleacetic acid (5-HIAA)
When you have symptoms suggestive of a carcinoid tumour such as flushing, diarrhoea, and/or wheezing. For individuals with a known serotonin-secreting carcinoid tumour, 5-HIAA may be monitored at intervals following treatment to check the treatment is reducing the carcinoid tumour.
You may be instructed to avoid certain foods and medications prior to this test. Please follow any instructions you are given.
This test measures the amount of 5-hydroxyindoleacetic acid (5-HIAA) in the urine. 5-HIAA is a muscle stimulant and the primary metabolite (breakdown product) of serotonin. In health, most serotonin is produced by the gastrointestinal (GI) tract where it regulates intestinal movements. The remainder is produced by the central nervous system where it functions to regulate mood, appetite and the wake/sleep cycle. After it has been used by the body, serotonin is broken down in the liver, and its metabolites, of which 5-HIAA is the major metabolite, are excreted in the urine. Normally, only small amounts of 5-HIAA is present in the urine. However, large quantities of serotonin and therefore 5-HIAA may be produced by some carcinoid tumours.
Carcinoid tumours are rare and typically slow-growing masses. The majority of carcinoid tumours form in the gastrointestinal tract but they can also form at other sites such as in the lungs and the pancreas. Many carcinoid tumours remain small and do not cause any symptoms. A small percentage of carcinoid tumours grow large enough to cause obstructions in the intestines or bronchial tubes of the lungs. Some carcinoid tumours can spread to other organs. The most common site of spread is to the liver.
About 19% of carcinoid tumours, primarily those found in the gastrointestinal tract, will produce enough serotonin to cause symptoms such as flushing of the face, diarrhoea, a rapid heart rate, and wheezing. This collection of symptoms is referred to as the carcinoid syndrome. Such symptoms will usually only appear after the tumour has spread to the liver. The serotonin that causes the carcinoid syndrome may be released continuously or intermittently and can lead to significantly increased quantities of 5-HIAA in the urine.
How is the sample collected for testing?
For the 24-hour urine collection, all urine should be saved for a 24-hour period. It is better to keep sample in a cool dark place. When complete the sample is taken as soon as possible to your GP or the laboratory for preservation. Pre-sample preparation is important for accurate 5-HIAA test results.
For more information, see ‘Common Questions’; ‘Is there anything else I should know’ below and talk to your doctor.
Is any test preparation needed to ensure the quality of the sample?
Pre-sample preparation is important for accurate 5-HIAA test results. Serotonin rich foods, such as avocados, bananas, pineapples, plums, walnuts, tomatoes and kiwi fruit, can interfere with 5-HIAA measurement and should be avoided for 3 days prior to and during urine collection. There are also a variety of medications that can affect the 5-HIAA test. It is important that those being tested talk to their healthcare provider before decreasing or discontinuing any medications.
How is it used?
5-HIAA may be requested by itself and very occasionally with blood serotonin to help diagnose and monitor carcinoid tumours. A 24-hour urine sample is preferred for the 5-HIAA test because the amount of 5-HIAA in the urine can vary throughout the day. In exceptional situations a random urine sample is sometimes tested, usually along with a urine creatinine level, when a 24-hour sample is not feasible. The random sample is not as accurate, however, and if the excess 5-HIAA is released intermittently, then it may be missed.
When is it requested?
This test is primarily requested when a patient has symptoms suggestive of a carcinoid tumour such as flushing (redness or feeling of warmth on your face and/or neck), chronic diarrhoea, shortness of breath and/or wheezing.
For individuals who have been diagnosed with and treated for a serotonin-secreting carcinoid tumour, 5-HIAA levels may be measured at intervals following treatment to monitor the effectiveness of the treatment (i.e. is the amount of serotonin being produced by the carcinoid tumour decreasing in response to treatment).
What does the test result mean?
Carcinoid Syndrome Symptoms and raised 5-HIAA
A significantly increased concentration of 5-HIAA in a 24-hour urine sample in a patient with carcinoid syndrome symptoms is suggestive but not diagnostic of a carcinoid tumour. In order to diagnose the condition, the tumour itself must be located (using scans/imaging) and a tissue biopsy may need to be examined. The doctor will frequently ask to repeat the urine collection and 5-HIAA test following an abnormal test result before requesting additional investigations. This is because the 5-HIAA concentration may be elevated in the urine due to interference from food or medication “false positive” 5-HIAA test. If a second 24-hour urine sample also demonstrated a raised 5-HIAA concentration, and all dietary/medication instructions were followed, it is more likely that this is a “true positive” 5-HIAA test and so further investigations are warranted to confirm the presence of a carcinoid tumour.
Carcinoid Syndrome Symptoms and normal 5-HIAA
A patient with symptoms may still have a carcinoid tumour even if the concentration of 5-HIAA is normal. The patient may have a tumour that does not secrete serotonin (non-functioning tumour) – a “true negative” 5-HIAA test. Alternatively, the tumour may secrete serotonin (and therefore 5-HIAA) intermittently, so the period of increased serotonin secretion is missed – a “false negative” 5-HIAA test. This is more likely to happen if a random urine sample is collected instead of a full 24-hour urine collection, or if the 24-hour urine collection is incomplete (not all the urine is collected over the 24-hour period). Some medications can reduce production of 5-HIAA and may cause a “false negative” 5-HIAA test.
No Carcinoid Syndrome Symptoms and raised 5-HIAA
Interpretation depends on why the test was performed. The 5-HIAA concentration may be elevated in the urine due to interference from food or medication - a “false positive” 5-HIAA test.
No Carcinoid Syndrome Symptoms and normal 5-HIAA
A patient with no symptoms of Carcinoid Syndrome and a normal 24-hour urine excretion of 5-HIAA is unlikely to have a serotonin-secreting carcinoid tumour. It does not rule out a non-functioning tumour.
Known Carcinoid Syndrome
In patients with known serotonin-secreting carcinoid tumours who are being monitored following treatment, decreasing concentrations of 5-HIAA indicate a response to treatment, while increasing or continued excessive concentrations indicate that the treatment may have not been successful.
Is there anything else I should know?
Serotonin-rich foods such as avocados, bananas, plantains, pineapples, plums, walnuts, tomatoes, kiwi fruit and health food supplements containing 5-hydroxytrytophen can increase 5-HIAA and should be avoided for three days prior to and during urine collection.
There are also a variety of medications that can affect the 5-HIAA test. Medications that can increase 5-HIAA include acetaminophen (paracetamol), caffeine, ephedrine (an ingredient found in some cough medicines), diazepam (Valium), nicotine, and phenobarbital. Medications that can decrease 5-HIAA include alcohol, imipramine, levodopa, MAO inhibitors, heparin, isoniazid, methyldopa, and tricyclic antidepressants. Patients should talk to their doctor before decreasing or discontinuing any medications.
Different tests are affected by different foods and medications so follow any local instructions (from your doctor or laboratory) that you are given.
Are there other markers of Carcinoid Syndrome?
- Serotonin itself (5-hydroxytryptamin) can be measured in platelet enriched plasma. It is a very sensitive marker for carcinoid syndrome but is difficult to measure reproducibly and there is a big difference in concentrations between different people. It is not routinely available in the UK.
- 5-HIAA can also be measured in plasma, in the future, once this marker is validated over time, this may become the more widely used test. Renal function must be taken into account when interpreting plasma or serum 5-HIAA concentrations
- Other metabolites of serotonin, the other major one being 5-hydroxytryptphol (5-HTOL), can also be measured in blood or urine. These metabolites are not routinely tested for.
- Chromogranin A concentrations are also increased in serotonin secreting carcinoid tumours, again results must be interpreted with caution
- A 24-hour urine collection for measurement of 5-HIAA is still the test recommended by UK and Ireland (and European) Neuroendocrine Tumour Societies.
Why do I have to collect my urine for 24 hours?
The concentration of 5-HIAA in the urine varies throughout the day and is inconsistently released by tumours. By collecting all urine for 24 hours, the amount of 5-HIAA in the urine can be averaged over the entire day. Increases in 5-HIAA will be detected more easily in a 24-hour sample than in a single random urine sample. In some laboratories, a random urine sample may be used instead of a 24-hour collection for monitoring patients with known carcinoid syndrome.
Will my results be accurate if I must continue to take my medication?
If the drug is one that can increase or decrease the amount of serotonin and 5-HIAA, then your results may be affected. However, it is up to your doctor and you to decide whether or not your medication can be safely stopped prior to and during the test collection. If your medications must be taken, then your doctor will interpret the test results with this in mind.
Are some people at a higher risk for developing a carcinoid tumour?
Carcinoid tumours are rare. They can affect anyone at any age but are most commonly diagnosed in persons over 60 years. Patients with a family history of Multiple Endocrine Neoplasia (MEN1), a genetic condition that increases a patient's risk of developing tumours in the endocrine system glands, may be at higher risk for developing a carcinoid tumour.