Vanillylmandelic Acid (VMA)
- Also Known As:
- Formal Name:
- Vanillylmandelic Acid
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At a Glance
Why Get Tested?
To help diagnose or rule out a neuroblastoma or other neuroendocrine tumor; to monitor the effectiveness of treatment
When To Get Tested?
When your child has a lump in the abdomen (abdominal mass), bruising around the eyes, trouble walking, or bone pain; when you have symptoms of increased catecholamine release, such as persistent or periodic high blood pressure, severe headaches, rapid heart rate, and sweating; when you have been treated for a neuroendocrine tumor, such as neuroblastoma
A 24-hour urine sample is preferred; sometimes a random urine sample is acceptable.
Test Preparation Needed?
This test is affected by caffeine, certain foods, certain drugs, and stresses. Inform your healthcare practitioner of any medications you are taking and follow any instructions you are given for things to avoid before sample collection.
What is being tested?
Vanillylmandelic acid (VMA) is one of the breakdown products (metabolites) of epinephrine (adrenaline) and norepinephrine. Epinephrine and norepinephrine belong to a group of similar hormones called catecholamines. This test measures the amount of VMA that is passed into the urine, typically over a 24-hour period, to detect excess epinephrine and norepinephrine. It is used to detect tumors called neuroblastomas and other …
Vanillylmandelic acid (VMA) is one of the breakdown products (metabolites) of epinephrine (adrenaline) and norepinephrine. Epinephrine and norepinephrine belong to a group of similar hormones called catecholamines. This test measures the amount of VMA that is passed into the urine, typically over a 24-hour period, to detect excess epinephrine and norepinephrine. It is used to detect tumors called neuroblastomas and other neuroendocrine tumors.
Catecholamines are 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 released are dopamine, epinephrine, and norepinephrine. 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. Norepinephrine also constricts blood vessels, increasing blood pressure, and epinephrine increases heart rate and metabolism.
After completing their actions, the catecholamines are metabolized to inactive compounds. Dopamine becomes homovanillic acid (HVA), norepinephrine breaks down into normetanephrine and VMA, and epinephrine becomes metanephrine and VMA. Both the hormones and their metabolites are eliminated from the body 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 a stressor.
Sometimes, tumors begin to form in the cells of the neuroendocrine system, which is made up of a combination of cells that produce hormones and nerve cells. These types of cells are found throughout the body in organs such as the lungs and the digestive system. Tumors that form in these cells are called neuroendocrine tumors.
Neuroendocrine tumors, such as neuroblastomas and pheochromocytomas, can sometimes produce large amounts of catecholamines, resulting in greatly increased concentrations of the hormones and their metabolites. The hormone releases can cause illness and signs and symptoms, such as persistent hypertension, severe headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities.
Neuroblastomas are rare cancers, but they are the most common cancers affecting infants, according to the American Cancer Society. About 700 new cases are diagnosed each year, primarily in babies one to two years old, with up to 90% of cases occurring in children under the age of five. Rarely, a baby may be born with a neuroblastoma. Arising from primitive nerve cells, these cancers can be found in the abdomen, adrenal glands, neck, chest, or pelvis. About two-thirds of the time, the tumors will have spread (metastasized) 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 without treatment. In other cases, their cells may spontaneously mature into normal nerves cells, turning the neuroblastoma into a benign ganglioneuroma or into a partially benign ganglioneuroblastoma.
Pheochromocytomas are rare tumors that arise primarily in the adrenal glands. According to the National Cancer Institute, they affect 2 to 8 people per million per year, primarily those in their thirties to fifties. Most pheochromocytomas are benign and do not spread from their original location, but some may metastasize 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, hypertension caused by the pheochromocytoma may damage body organs, such as the kidneys and heart, and raise the risk of an affected person having a stroke or heart attack. Pheochromocytomas 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. The preferred tests for pheochromocytomas are plasma free metanephrines, urine metanephrines, and urine or plasma catecholamine tests. However, the VMA test may still be ordered along with one or more of these tests to help detect and rule out a pheochromocytoma.
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 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 foods, certain drugs, and stresses. It is important to inform your healthcare practitioner of any medications you are taking, 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 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.
When is it ordered?
VMA testing is ordered when a healthcare 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.
What does the test result mean?
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 healthcare 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 healthcare 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.
Is there anything else I should know?
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 healthcare 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.
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 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.
How long will it take for results?
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.
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 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 healthcare practitioner will interpret the test results with this in mind.
Are some people at a higher risk for developing a pheochromocytoma or neuroblastoma?
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.
On This Site
Elsewhere On The Web
Cancer.Net: Neuroendocrine tumor
American Cancer Society: Neuroblastoma
National Cancer Institute: Neuroblastoma Treatment (PDQ®)
National Cancer Institute: Pheochromocytoma Treatment (PDQ®)
Sources Used in Current Review
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Mayo Clinic staff (2014 May 2). Pheochromocytoma. Mayo Clinic. Available online at http://www.mayoclinic.com/print/pheochromocytoma/DS00569/DSECTION=all&METHOD=print. Accessed March 2017.
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Sources Used in Previous Reviews
Pagana, K. D. & Pagana, T. J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 987-990.
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