Plasma Free Metanephrine
A rare tumor called a pheochromocytoma can produce large amounts of catecholamines, resulting in significantly increased concentrations of metanephrine and normetanephrine in both the blood and urine. About 90% of pheochromocytomas form in the adrenal glands and, while a few are cancerous, most are benign – they continue to grow but usually do not spread beyond their original location. The catecholamines produced by pheochromocytomas can cause persistent hypertension and/or paroxysms (bouts) of severe high blood pressure. This can cause symptoms such as headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities. Left untreated, the symptoms may worsen as the pheochromocytoma grows. Over time, hypertension caused by the tumor may damage organs such as the kidneys and heart and raise the risk of an affected patient having a stroke or heart attack.
Several tests, including plasma free metanephrines, can detect the presence of pheochromocytomas. Although they are rare, it is important to diagnose pheochromocytomas because they cause a potentially curable form of hypertension. In most cases, the tumors can be surgically removed, which eliminates the high blood pressure and its associated symptoms and complications.
How is the sample collected for testing?A blood sample is obtained by inserting a needle into a vein in your arm. Although there is some disagreement over the specifics of how the sample should be collected, you may be asked to lie down and rest quietly for 15 – 30 minutes prior to sample collection, and your blood may be collected while you are lying down. In other circumstances, you may just be seated upright with little or no rest time before the sample collection.
Is any test preparation needed to ensure the quality of the sample?Preparation for the test is important for accurate results. You should discontinue epinephrine and epinephrine-like drugs for at least 1 week before the test, stop using acetaminophen 48 hours beforehand, and fast for 8-10 hours prior to collection. It is especially important not to have any caffeine containing food (soda, chocolate), coffee (including decaf), tobacco (smoking cigarettes or cigars), tea, or alcohol for at least 4 hours before specimen collection. Talk to your doctor about all the medications you are taking. Since several different drugs may interfere with the test, he may instruct you to withhold all medications except those that are necessary for one week prior to the test. However, do not stop taking any medications without first consulting your doctor.
How is it used?Plasma free metanephrines is a relatively new test, and there is not yet widespread consensus on exactly how it should be used. Studies have shown that plasma testing is more sensitive than 24-hour urine catecholamines or metanephrines testing. However, this sensitivity brings with it a certain number of false positive results, especially when the test is ordered on patients in whom a pheochromocytoma is unlikely. For this reason, plasma free metanephrines is not recommended as a routine test for the general public. Its primary use is in symptomatic patients when urine testing does not provide clear-cut results. Since both blood and urine test results may be affected by stress, caffeine, alcohol, and certain drugs, a doctor may investigate a positive result by evaluating a patient’s stresses and intake, alter or minimize these influences, and then repeat the tests to confirm the original findings.
Occasionally, the test may be ordered on an asymptomatic person if an adrenal 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. These tumors may recur, and there is a genetic link in some cases.
When is it ordered?The plasma free metanephrines test is primarily 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 hypertension and persistent or recurring 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 as patients with 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 may also be used as a monitoring tool when a patient has been treated for a previous pheochromocytoma.
What does the test result mean?Since the plasma free metanephrines test is very sensitive and pheochromocytomas are rare, a doctor may see more false positives with this test than true positives. The negative predictive value of the test, however, is very good. This means that if the concentrations of the free metanephrines are normal in the blood, then it is very unlikely that a patient has a pheochromocytoma.
If a symptomatic or asymptomatic patient has only moderately elevated free metanephrines, then a doctor may re-evaluate the patient’s medications, diet, and stress level to look for interfering substances. He may then re-test the patient, perhaps along with 24-hour urine catecholamine testing and/or metanephrine testing, to determine whether the free 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 may be an indication that the tumor is recurring.
Is there anything else I should know?The majority of pheochromocytomas are found in the adrenal glands and most of the rest are found within the abdominal cavity. While the plasma free metanephrines test can help detect and diagnose pheochromocytomas, it cannot tell the doctor where the tumor is or whether it is benign or malignant (although most are benign).
An increased risk for developing pheochromocytomas can be inherited. MEN-1 and MEN-2 (Multiple Endocrine Neoplasia, types 1 and 2) syndromes are groups of conditions associated with alterations in specific genes. They increase the lifetime risk that those affected will develop tumors in one or more of their endocrine glands.
Several medications may interfere with the test. Consult your doctor as to which drugs you may safely discontinue before being tested. Also, caffeine containing foods such as coffee, soda and chocolate as well as cigarette and cigar smoking may interfere with the test and should be avoided prior to testing.
Can I have more than one pheochromocytoma at once?
Does the amount of plasma free metanephrines detected correspond to the size of the tumor?No, it has more to do with the characteristics of the tumor. Even a very small tumor can produce large amounts of catecholamines.
Is it really necessary to follow the dietary restrictions and lie down before testing?There is some disagreement over the specifics of how the sample should be collected. However, it is known that the level of catecholamines (and their metabolites) in the blood is affected by diet and stress levels. For test accuracy, interfering substances need to be avoided and the patient's physical and emotional stress levels should be as low as possible.