When your child has an abdominal mass, bruising around the eyes, trouble walking, or bone pain; when you have symptoms of increased catecholamine release, such as persistent or episodic high blood pressure, severe headaches, rapid heart rate, and sweating; when you have been treated for a neuroendocrine tumour, such as neuroblastoma or phaeochromocytoma
This test is affected by caffeine, certain drugs, and stresses. Inform your doctor of any medications you are taking and follow any instructions you are given for things to avoid before sample collection.
Vanillylmandelic acid (VMA) is one of the metabolites of the catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine). This test measures the amount of VMA that is excreted into the urine, typically over a 24-hour period, to detect excess catecholamine production.
Catecholamines are a group of similar hormones produced in the central portion of the adrenal glands, the adrenal medulla. Adrenal glands are small triangular organs located on top of each kidney. The primary catecholamines that they release are dopamine, adrenaline, and noradrenaline. These hormones are released into the bloodstream in response to physical or emotional stress. They help transmit nerve impulses in the brain, increase glucose and fatty acid release for energy, dilate bronchioles, and dilate the pupils. Noradrenaline also constricts blood vessels, increasing blood pressure, and adrenaline increases heart rate and metabolism. After completing their actions, the catecholamines are metabolised to inactive compounds. Dopamine becomes 3-methoxytyramine (3-MT) and homovanillic acid (HVA), noradrenaline breaks down into normetadrenaline and VMA, and adrenaline becomes metadrenaline and VMA. Both the hormones and their metabolites are excreted in the urine.
VMA is usually present in the urine in small fluctuating amounts that only increase appreciably during and shortly after the body is exposed to stress. Neuroblastomas, phaeochromocytomas, and other neuroendocrine tumours, however, can produce large amounts of catecholamines, resulting in greatly increased concentrations of the hormones and their metabolites. The hormone releases can cause persistent hypertension, severe headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities.
Neuroblastomas are the most common extra cranial solid tumour in childhood and most frequently diagnosed during infancy. The incidence of neuroblastoma is 10.2 cases per million children under 15 years of age. Up to 90 per cent of cases occur in children under the age of five. Rarely, a baby may be born with a neuroblastoma. Arising from primitive nerve cells, the cancers can be found in the abdomen (~65 per cent of primary tumours), adrenal glands, neck, chest, or pelvis. About two-thirds of the time, the tumours will have metastasised and moved to other parts of the body by the time they are diagnosed. Once detected, many neuroblastomas can be successfully treated. In some cases, neuroblastomas may disappear on their own or their cells may spontaneously mature into normal nerves cells, turning the neuroblastoma into a benign ganglioneuroma or into a partially benign ganglioneuroblastoma.
Phaeochromocytomas are rare tumours that arise primarily in the adrenal glands. According to the National Cancer Institute, they affect 2 to 5 people per million per year, primarily those in their thirties to fifties. Most phaeochromocytomas are benign and do not spread from their original location (~85 per cent), but some may metastasise and move to other organs within the body. Left untreated, they continue to grow and produce catecholamines, and hormone-related symptoms continue to worsen. Over time, the hypertension that the phaeochromocytoma causes may damage body organs, such as the kidneys and heart, and raise the risk of an affected person having a stroke or heart attack. Phaeochromocytomas are important to diagnose because they represent a potentially curable form of hypertension. In most cases, they can be removed and/or treated to reduce or eliminate the associated symptoms and complications.
The VMA test, along with other tests for catecholamines and their metabolites, can be used to help detect the presence of neuroblastomas and phaeochromocytomas.
How is the sample collected for testing?
For a 24-hour urine collection, all of the urine produced during a 24-hour period should be collected into a container and saved. It is important that the sample be refrigerated during this time period. A single urine sample is collected for a random urine test.
Is any test preparation needed to ensure the quality of the sample?
This test is affected by caffeine, certain drugs, and stresses. It is important to inform your healthcare professional of any medications being taken, including herbal supplements and over-the-counter products, and to follow any instructions provided for things to avoid before sample collection.
How is it used?
The vanillylmandelic acid (VMA) test is primarily used to detect and rule out neuroblastomas in children with an abdominal mass or other symptoms suggestive of the disease. It may be requested along with an homovanillic acid (HVA) test to help diagnose a neuroblastoma, to monitor the effectiveness of treatment, and to monitor for neuroblastoma recurrence. A urine creatinine test is typically also requested, especially with random urine testing, and tests results are frequently reported as VMA-to-creatinine and HVA-to-creatinine ratios. Since creatinine is a substance that is excreted in the urine at a relatively constant rate, it serves as a comparison to the rate of VMA and HVA excretion.
A VMA test was once frequently requested to detect phaeochromocytomas, but the preferred tests are now plasma free metadrenalines, urine metadrenalines, and urine catecholamine tests. The VMA test may still be requested along with one or more of these tests to help detect and rule out a phaeochromocytoma.
When is it requested?
VMA testing is requested when a doctor either suspects that a child has a neuroblastoma or wants to rule out the possibility. The doctor may request it, along with an homovanillic acid (HVA) test, when a child has an abdominal mass or other symptoms suggestive of a neuroblastoma. These signs and symptoms can vary depending upon their location and may vary over time:
- Most neuroblastomas are located in the abdomen, so the most common symptom is an unusual non-tender lump or mass in that area. Others include abdominal pain and lack of appetite.
- Sometimes a tumour in the neck can cause swelling and affect swallowing or breathing.
- If the tumour presses on nerves by the spine, it may affect the child's ability to walk.
- If it has spread to the bones (metastasised), it may cause bone pain, and if to the marrow, it may affect blood cell production, causing fatigue, pallor, and bleeding.
A neuroblastoma can also cause bruising around the eyes and drooping eyelids, bluish purple spots on the skin, and can sometimes affect bladder and bowel function. Rarely, it may cause muscle spasms and rapid eye movements referred to as "dancing eyes, dancing feet."
The VMA test may also be requested when a child has been treated for a neuroblastoma and requested periodically to monitor for recurrence. A VMA test may be requested along with one or more metadrenaline or catecholamine tests when a doctor suspects that a person has a phaeochromocytoma. They may be requested when a person has persistent or recurring hypertension that is not responding to conventional therapies, to monitor the effectiveness of treatment for a phaeochromocytoma, and periodically to monitor for recurrence.
What does the test result mean?
Since the VMA test is sensitive to many outside influences, and neuroblastomas and phaeochromocytomas are rare, a doctor may see more false positives with this test than true positives. When a person has large amounts of VMA in the urine, it is not diagnostic of a condition; it is an indication that further investigation is necessary.
Intense emotional and physical stresses can cause moderate to large temporary increases in VMA levels. The doctor must evaluate the child or adult as a whole – their physical condition, emotional state, prescribed medications, and any over-the-counter products that they are taking. When interfering substances and/or conditions are found and resolved, the doctor will frequently re-test the individual to determine whether the VMA concentration is still elevated. The doctor may also request other catecholamine and metadrenaline testing and imaging tests, such as an MRI, to help find the tumour(s).
If a child or adult is being treated for a neuroblastoma or phaeochromocytoma, then decreasing VMA concentrations indicate a response to treatment; stable or increasing levels indicate that the treatment is not effective. If a VMA concentration is initially normal and then increases in a person who has had a previous neuroblastoma or phaeochromocytoma, then it is likely that the tumour is recurring.
About 90% of children with a neuroblastoma will produce excess VMA and homovanillic acid. If a VMA and other catecholamine and metadrenaline testing are normal, then it is less likely that a child has a neuroblastoma or an adult has a phaeochromocytoma, but it cannot be ruled out. The tumours do not necessarily produce catecholamines at a constant rate, so increases in the hormones and metabolites will fluctuate in the urine and may not be increased in the sample tested. This is especially true when a single random urine sample is tested.
Is there anything else I should know?
The amount of VMA produced does not necessarily correspond to the size of the tumour. This is a physical characteristic of the tumour tissue. The total amount of VMA produced will tend to increase, however, as the tumour increases in size.
A doctor will sometimes evaluate a VMA-to-HVA ratio with a neuroblastoma. A low ratio is associated with a poorer prognosis.
A variety of medications can interfere with VMA testing, but those being tested should always consult with their doctor before discontinuing any prescribed medications. Some of the drugs that can interfere include appetite suppressants, caffeine, clonidine, disulfiram, histamine, imipramine, insulin, adrenaline, levodopa, lithium, morphine, MAO inhibitors, nitroglycerin, and rauwolfia alkaloids. The effects of these drugs on VMA results will be different from person to person and are often not predictable.
Why do I have to collect my urine for 24 hours?
The reason that you need to collect your urine over a 24-hour period is because the amount of VMA excreted in the urine changes during the course of a day. By collecting all urine for 24 hours, the amount of VMA measured can be averaged over the entire day and will give a better indication of whether levels are increased or not.
Can this test be done at my doctor's surgery?
No, this test requires specialised equipment and must be performed in a laboratory. Not every laboratory will perform this assay; in some cases, your sample will need to be sent to a reference laboratory.
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 VMA, 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 drugs 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 phaeochromocytoma or neuroblastoma?
People with a family history of multiple endocrine neoplasia (MEN 2), a genetic condition that increases a person's risk of developing tumours in the endocrine system glands, may be at higher risk for developing a phaeochromocytoma, having more than one, and developing it at a younger age. Most cases of neuroblastomas are considered "sporadic," but about 1 to 2 per cent of cases may be due to inherited factors. Those with a strong family history may have an increased risk.