Urine metanephrine testing measures the amount of both metanephrine and normetanephrine. These metabolites are usually present in the urine in small fluctuating amounts that increase appreciably during and shortly after the body is exposed to a stressor. Pheochromocytomas and other neuroendocrine tumors, however, can produce large amounts of catecholamines, resulting in greatly increased concentrations of the hormones and their metabolites in both the blood and urine. The catecholamines that a pheochromocytoma produces can cause persistent hypertension (high blood pressure) and/or bouts or episodes of severe hypertension. Other symptoms of catecholamine release include headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities.
About 90% of pheochromocytomas are located in the adrenal glands. While a few are cancerous, most are benign – they do not spread beyond their original location - although most do continue to grow. Left untreated, the symptoms may worsen as the tumor grows and, over a period of time, the hypertension that the pheochromocytoma causes may damage body organs, such as the kidneys and heart, and raise the risk of an affected patient having a stroke or heart attack.
The metanephrine test can be used to help detect the presence of pheochromocytomas. Although, according to the National Cancer Institute, only about 800 cases a year are diagnosed in the U.S., it is important to diagnose and treat these rare tumors because they cause a potentially curable form of hypertension. In most cases, the tumors can be surgically removed and/or treated to significantly reduce the amount of catecholamines being produced and to reduce or eliminate associated symptoms and complications.
How is the sample collected for testing?For the 24-hour urine collection, all of your urine should be saved for a 24-hour period. It is important that the sample be refrigerated during this time period.
Is any test preparation needed to ensure the quality of the sample?Foods such as coffee (including decaf), tea, chocolate, vanilla, bananas, oranges and other citrus fruits should be avoided for several days prior to the test and during collection. There are also many medications that can potentially affect test results. Talk to your doctor about any prescriptions and over-the-counter drugs and supplements that you are taking. Wherever possible, those that are known to interfere should be discontinued prior to and during sample collection. Emotional and physical stresses and vigorous exercise should be minimized prior to and during sample collection as they can increase catecholamine secretion.
How is it used?Urine metanephrine testing is primarily used to help detect and rule out pheochromocytomas in symptomatic patients. It may also be ordered to help monitor the effectiveness of treatment when a pheochromocytoma is discovered and removed and to monitor for recurrence. Urine metanephrine testing may be ordered by itself or along with a plasma metanephrine test. Plasma and urine catecholamine testing may also be ordered, either along with urine metanephrines or as follow-up tests. Since catecholamine secretion tends to fluctuate over time, a 24-hour urine test for metanephrines or catecholamines may detect excess production that is missed with the blood test. It is up to the doctor to decide which test or test combinations will give him the most information. In many cases, urine and plasma metanephrines may be preferred as they are usually present in greater quantities than catecholamines in the urine and can persist in the blood even when catecholamine levels have returned to normal.
Since these tests are affected by drugs, foods, and stresses, there will be a certain number of false positives. For this reason, metanephrine testing is not recommended as a screen for the general public. Doctors will frequently investigate a positive result by evaluating a patient’s stresses and intake, work to alter or minimize these influences, and then repeat the test to confirm the original findings.
Occasionally, metanephrine testing may be ordered on an asymptomatic person if an adrenal or neuroendocrine tumor is detected during a scan that is done for another purpose or if the patient has a strong personal or family history of pheochromocytomas (as they may recur and there is a genetic link in some cases).
When is it ordered?Urine metanephrines are ordered when a doctor either suspects that a patient has a pheochromocytoma or wants to rule out the possibility. He may order it when a patient has persistent or recurring hypertension along with symptoms such as headaches, sweating, flushing, and rapid heart rate. It may also be ordered when a patient has hypertension that is not responding to treatment. Since the hormone production from a pheochromocytoma is not regulated by the body, patients who have hypertension due to a pheochromocytoma are frequently resistant to conventional therapies.
Occasionally, the test may be ordered when an adrenal tumor is detected incidentally or when a patient has a family history of pheochromocytomas. It also may be used as a monitoring tool when a patient has been treated for a previous pheochromocytoma.
What does the test result mean?Because the metanephrine test is sensitive to many outside influences and pheochromocytomas are rare, a doctor may see more false positives with this test than true positives. If a symptomatic patient has large amounts of metanephrines in his urine, further investigation is indicated. If there are no interfering substances or stresses identified, then there is a good possibility that he may have a pheochromocytoma. The doctor may order plasma metanephrine and/or urine or plasma catecholamine testing to help confirm the initial findings. If these are also elevated, then imaging tests such as an MRI may be ordered to help find the tumor(s).
Serious illnesses and stresses can cause moderate to large temporary increases in metanephrine levels. Doctors must evaluate the patient as a whole - his physical condition, emotional state, medications, and diet. When interfering substances and/or conditions are found and resolved, the doctor will frequently re-test the patient to determine whether the metanephrines are still elevated. If they are, then he may order imaging scans; if they are not, then it is unlikely that the patient has a pheochromocytoma.
If levels are elevated in a patient who has had a previous pheochromocytoma, it is likely that either treatment was not fully effective or that the tumor is recurring.
The negative predictive value of the test is relatively good. This means that if metanephrine concentrations are normal, then it is unlikely that apatient has a pheochromocytoma.
Is there anything else I should know?While metanephrine testing can help detect and diagnose pheochromocytomas, it cannot tell the doctor how big the tumor is, where it is, how many tumors are present, or whether or not the tumor(s) are benign – although most are. Even small tumors can produce large amounts of catecholamines.
It is very important to talk to your doctor before discontinuing any prescribed medications. He will work with you to identify interfering substances and drug treatments to determine which of them can be safely interrupted and which must be continued for your well-being. Some of the substances that can interfere with metanephrine testing include: acetaminophen, aminophylline, amphetamines, appetite suppressants, coffee, tea, and other forms of caffeine, chloral hydrate, clonidine, dexamethasone, diuretics, epinephrine, ethanol (alcohol), insulin, imipramine, lithium, methyldopa (Aldomet), MAO (monoamine oxidase) inhibitors, nicotine, nitroglycerine, nose drops, propafenone (Rythmol), reserpine, salicylates, theophylline, tetracycline, tricyclic antidepressants, and vasodilators. The effects of these drugs on metanephrine testing will be different from patient to patient and are often not predictable.
Can I have tumors in both of my adrenal glands?
If I avoid all of the interfering substances mentioned, could I prevent a pheochromocytoma?No. Drugs and some dietary components may interfere with accurate test results, but they do not cause or exacerbate the tumor itself.
Why haven't I heard about pheochromocytomas?
Will my doctor ever test for HVA or VMA?
Is it really necessary to collect urine for 24 hours?Yes, for accurate test results it is essential that all of the urine be collected. Because the catecholamines are released at varying times, the one sample not included might be the one with the most metanephrines in it.