What is being tested?
Metanephrine and normetanephrine are breakdown products (metabolites) of the catecholamines epinephrine (adrenaline) and norepinephrine. This test measures the amounts of metanephrine and normetanephrine that are released into the urine over a 24-hour period.
Catecholamines are produced by the adrenal glands (as hormones), small triangular organs located on top of each kidney, and by cells of the sympathetic nervous system (called neurotransmitter substances or neurotransmitters). The primary catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine. Catecholamines are released in response to physical or emotional stress. They help transmit nerve impulses in the brain, increase glucose and fatty acid release for energy, dilate small air passages in the lungs called bronchioles, and dilate the pupils. Norepinephrine also constricts blood vessels, which increases blood pressure, and epinephrine increases heart rate and the rate at which the body uses energy (metabolism).
After completing their actions, the catecholamines are broken down to form inactive compounds. Epinephrine breaks down into metanephrine and vanillylmandelic acid (VMA), and norepinephrine becomes normetanephrine and VMA. Both the hormones and their metabolites are eliminated from the body in the urine.
Catecholamines and their breakdown products are normally present in the urine in small fluctuating amounts that increase appreciably during and shortly after a stressful situation.
However, rare tumors of the adrenal gland called pheochromocytomas and rare tumors outside the adrenal glands called paragangliomas can produce large amounts of catecholamines and their metabolites, resulting in greatly increased concentrations in both the blood and urine. (These syndromes are often grouped together and abbreviated as PPGL). This can cause persistent or episodic periods of hypertension, which may lead to severe headaches. Other symptoms include heart palpitations, sweating, nausea, anxiety, and tingling in the hands and feet.
Pheochromocytomas and paragangliomas are rare. While a few are cancerous, most are benign and do not spread beyond their original location. Left untreated, however, these tumors may continue to grow and the symptoms may worsen. Over time, the hypertension caused by the excess hormones may cause kidney damage, heart disease, and raise the risk of a stroke or heart attack.
Although they are rare, it is important to diagnose and treat these tumors because they cause a potentially curable form of hypertension. In most cases, the tumors can be surgically removed and/or treated to eliminate or 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 urine should be saved for a 24-hour period. Empty the bladder completely without collecting. Then collect urine for 24 hours only – no more than 24 hours. It is important that the sample be refrigerated during this time.
Is any test preparation needed to ensure the quality of the sample?
Catecholamine levels, and by extension the levels of their metabolites, are affected by various drugs, foods and stresses. Preparation for the test is important to ensure that an appropriate sample is collected and for correct interpretation of results. Follow any instructions given by your health care practitioner or the collection site or laboratory.
- You should talk to your health care provider about prescription medications and over-the-counter drugs and supplements that you are taking. It may be necessary to discontinue medications for some time prior to the test.
- However, you should not stop taking any medications without consulting your healthcare provider. Your health practitioner will work with you to identify potentially interfering substances and drug treatments and to determine which of them can be safely interrupted and which must be continued for your well-being.
- You will also be instructed on what foods to avoid.
- Avoid emotional and physical stresses and vigorous exercise prior to and during sample collection as they can increase catecholamine release and therefore affect metanephrine levels.
How is the test used?
Urine metanephrines testing is used to help detect or rule out the presence of a rare tumor called a pheochromocytoma or a paraganglioma that releases excess metanephrines. Since these tumors (PPGL) produce these hormones in excess, measuring the amount in the blood and/or urine may help detect the tumors. Testing may also be used when a tumor has been treated or removed to monitor for recurrence.
The Endocrine Society recommends using a test for plasma free metanephrines or urine metanephrines to evaluate an individual for PPGL.
- The blood test may be most useful when you have persistent hypertension or are currently experiencing a sudden burst (paroxysm) of hypertension. This is because the hormones do not stay long in the blood. They are used by the body and rapidly broken down (metabolized) and/or then eliminated.
- Urine testing measures the total amount of metanephrines released into the urine in 24 hours. Since the hormone levels may fluctuate significantly during this period, the urine test may detect excess production that is missed with a blood test.
However, your health care practitioner may select any one (or more than one) of these tests depending on your signs and symptoms, family history, and/or genetic profile.
When is it ordered?
Urine metanephrines are ordered when your health care provider either suspects that you have a tumor that produces catecholamines or wants to rule out the possibility. It may be ordered when you (especially if you are younger than age 40) have sudden bursts (paroxysms) of signs and symptoms such as:
- High blood pressure, especially when your hypertension is not responding to treatment (people with these tumors are frequently resistant to standard therapies)
- Severe headaches
- Rapid heart rate (palpitations)
Testing may also be ordered when a tumor that releases catecholamines has been treated or removed to monitor for recurrence.
Occasionally, the test may be ordered when an adrenal tumor is detected by chance, such as during a scan conducted for another purpose, or when you have an inherited (genetic) risk or a family history of pheochromocytomas.
What does the test result mean?
Normal urine levels of metanephrine and normetanephrine mean it is unlikely that you have a tumor that produces catecholamines. This test is very sensitive and these tumors are rare, so the negative predictive value of the test is very good.
Elevated levels of metanephrine and normetanephrine when you have signs and symptoms suggest the presence of a tumor. Generally, two times the upper limit of normal is considered positive for total metanephrine. If levels are elevated after you have been treated for one of these tumors, it may be an indication that the treatment was not fully effective or that the tumor is recurring and appropriate follow up is needed.
The test for metanephrines is very sensitive and false positives do occur. The test is affected by stress, drugs, smoking, and various foods. If you have only moderately elevated metanephrines, then your healthcare provider may re-evaluate your medications, diet, and stress level to look for interfering substances or conditions. Once these are resolved, you may be tested again to determine whether the metanephrines are still elevated.
Is there anything else I should know?
While metanephrines testing can help detect and diagnose tumors that release catecholamines, it cannot tell your health care provider how big the tumor is, where it is located, how many tumors are present, or whether or not the tumor(s) are benign (although most are benign). Imaging studies may be used to locate the tumor and testing may be used to determine potential malignancy.
About 25% of PPGL occur in the setting of a hereditary syndrome associated with alterations in specific genes. These genetic syndromes have thus been identified as carrying an increased tumor risk. Examples include MEN-1 and MEN-2 (Multiple Endocrine Neoplasia, types 1 and 2) syndromes. (For more information on these, see Genetics Home Reference: Multiple endocrine neoplasia.)
Can I have more than one pheochromocytoma at once?
Yes. Usually a single adrenal tumor will arise in one gland or the other, but multiple tumors can form. This is more likely in people with a strong family history of pheochromocytomas. You may have a tumor in each adrenal gland or occasionally in other locations.
Does the amount of urine 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 collect urine for 24 hours?
Yes, for accurate test results, it is essential that all of the urine be collected. Catecholamines are released at varying times, so the one sample not included might be the one with the most metanephrines in it. For general instructions, read about the 24-hour urine collection.