Vanillylmandelic Acid (VMA)

The vanillylmandelic acid (VMA) test is primarily used to detect and rule out tumors called neuroblastomas in children with an abdominal mass or other symptoms suggestive of the disease. It may be ordered 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 ordered, 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 passed into the urine at a relatively constant rate, it serves as a comparison to the amounts of VMA and HVA.

A VMA test was once frequently ordered to detect pheochromocytomas, but the preferred tests are now plasma free metanephrines, urine metanephrines, and urine or plasma catecholamine tests. The VMA test may still be ordered along with one or more of these tests to help detect and rule out a pheochromocytoma.

VMA testing is ordered when a health care practitioner either suspects that a child has a neuroblastoma or wants to rule out the possibility. A healthcare practitioner may order 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 belly, 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 tumor in the neck can cause swelling and affect swallowing or breathing.
• If the tumor presses on nerves by the spine, it may affect the child’s ability to walk.
• If it has spread to the bones (metastasized), 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 ordered when a child has been treated for a neuroblastoma and ordered periodically to monitor for recurrence.

A VMA test sometimes may be ordered along with one or more metanephrine or catecholamine tests when a healthcare practitioner suspects that a person has a pheochromocytoma. They may be ordered when a person has persistent or recurring hypertension that is not responding to conventional therapies, to monitor the effectiveness of treatment for a pheochromocytoma, and periodically to monitor for recurrence.

Since the VMA test is sensitive to many outside influences, and neuroblastomas and pheochromocytomas are rare, the false-positive rate for this test is high – greater than 15%. When a person has large amounts of VMA in his or her 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 health care practitioner must evaluate the child or adult as a whole – his or her physical condition, emotional state, prescribed medications, and any over-the-counter products that the person is taking. When interfering substances and/or conditions are found and resolved, the health care practitioner will frequently re-test the person to determine whether the VMA is still elevated. The healthcare practitioner may also order other catecholamine and metanephrine testing, genetic mutation testing, and imaging tests such as an MRI to help find the tumor(s).

If a child or adult is being treated for a neuroblastoma or pheochromocytoma, 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 pheochromocytoma, then it is likely that the tumor is recurring.

About 90% of children with a neuroblastoma will produce excess VMA and homovanillic acid. If a VMA and other catecholamine and metanephrine testing are normal, then it is less likely that a child has a neuroblastoma or an adult has a pheochromocytoma, but it cannot be ruled out. The tumors 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.

The amount of VMA produced does not necessarily correspond to the size of the tumor. This is a physical characteristic of the tumor tissue. The total amount of VMA produced will tend to increase, however, as the tumor increases in size.

A health care practitioner 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 healthcare practitioner before discontinuing any prescribed medications. Some of the drugs that can interfere include appetite suppressants, caffeine, clonidine, disulfiram, histamine, imipramine, insulin, epinephrine, 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.

The reason that you need to collect your urine over a 24-hour period is because the amount of VMA released 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.

That depends on the laboratory performing the test. This test requires specialized equipment and not every laboratory offers the test. In some cases, your sample will need to be sent to a reference laboratory and it may take several days for results to be available.

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 healthcare practitioner 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 health care practitioner will interpret the test results with this in mind.

People with a family history of multiple endocrine neoplasia (MEN2), a genetic condition that increases a person’s risk of developing tumors in the endocrine system glands, may be at higher risk for developing a pheochromocytoma, having more than one, and developing it at a younger age. Most cases of neuroblastomas are considered “sporadic,” but about 1% to 2% of cases may be due to inherited factors such as a mutation in the ALK gene. Those with a strong family history may have an increased risk.