5-Hydroxyindoleacetic acid (5-HIAA)

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.

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).

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.

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.

• 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.