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Urine Metanephrines


At a Glance

Why Get Tested?

To help diagnose or rule out a rare adrenal tumor called a pheochromocytoma or a rare extra-adrenal tumor called a paraganglioma; these tumors produce excess hormones called catecholamines, which are broken down to metanephrines.

When to Get Tested?

When you have signs and symptoms of increased catecholamines release, such as sudden bursts (paroxysms) of high blood pressure (hypertension), severe headaches, rapid heart rate (palpitations), sweating, tremors and pallor; when hypertension does not respond to standard treatments; when the signs and symptoms occur in a relatively young person (younger than age 40) and when there is a family history of hypertension; when your healthcare provider suspects you may have a tumor that is releasing or may release excess catecholamines

Sample Required?

A 24-hour urine collection

Test Preparation Needed?

These tests are affected by certain drugs, foods, and stresses. Inform your healthcare provider of any medications you are taking and follow any preparation instructions you are given before sample collection.

The Test Sample

What is being tested?

Thumbnail diagram of the adrenal gland

Metanephrine and normetanephrine are breakdown products (metabolites) of epinephrine (adrenaline) and norepinephrine. Epinephrine and norepinephrine belong to a group of similar hormones called catecholamines. This test measures the amounts of metanephrine and normetanephrine that are released into the urine over a 24-hour period.

Catecholamines are produced in the adrenal medulla, the central portion of the adrenal glands, small triangular organs located on top of each kidney and by cells of the sympathetic nervous system. The primary catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine. These hormones are released into the blood 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 metabolites are normally present in the urine in small fluctuating amounts that increase appreciably during and shortly after a stressful situation.

However, rare adrenal tumors called pheochromocytomas and rare extra-adrenal tumors called paragangliomas can produce large amounts of the hormones and their metabolites, resulting in greatly increased concentrations in both the blood and urine. 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.

The Endocrine Society recommends that a test for plasma free metanephrine or urine metanephrine be used as the primary test to help detect the presence of pheochromocytomas and paragangliomas. 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. It is important that the sample be refrigerated during this time period.

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 the healthcare provider or the collection site or laboratory.

  • People being tested should talk to their healthcare provider about prescription medications and over-the-counter drugs and supplements that they are taking. It may be necessary to discontinue medications for some time prior to the test. However, the patient should not stop taking any medications without consulting their healthcare provider.
  • The patient will also be instructed on what foods to avoid.
  • Emotional and physical stresses and vigorous exercise should be minimized prior to and during sample collection as they can increase catecholamine secretion and therefore affect metanephrine levels.

The Test

How is it used?

Urine metanephrines testing is used to help detect or rule out the presence of a rare tumor called a pheochromocytomas or a paraganglioma that releases excess metanephrines. Testing may also be used when a tumor has been treated or removed to monitor for recurrence.

The metanephrines - metanephrine and normetanephrine - are breakdown products (metabolites) of epinephrine (adrenaline) and norepinephrine. Epinephrine and norepinephrine are hormones called catecholamines that are released into the blood in response to physical or emotional stress and help regulate the flow and pressure of blood throughout the body. (For more on this, see the "What is being tested?" section.) Since pheochromocytomas and paragangliomas produce these hormones in excess, measuring the amount in the blood and/or urine may help detect the tumor.

The Endocrine Society recommends using a test for plasma free metanephrines or urine metanephrines to evaluate an individual for a pheochromocytomas or paragangliomas. The blood test may be most useful when the person has persistent hypertension or is 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 the blood test.

The test for metanephrines is very sensitive and false positives do occur. The test is affected by stress, drugs, smoking and various foods such as caffeine-containing drinks and alcohol. If a person has only moderately elevated metanephrines, then the healthcare provider may re-evaluate the person's medications, diet, and stress level to look for interfering substances or conditions. Once these are resolved, the person may be tested again to determine whether the metanephrines are still elevated and take appropriate action. Sometimes the 24-hour urine metanephrines test will be done in conjunction with plasma free metanephrines testing and/or followed by catecholamines testing to help decide if a catecholamine-secreting tumor is present.

When is it ordered?

Urine metanephrines are ordered when a healthcare provider either suspects that someone has a catecholamine-secreting tumor or wants to rule out the possibility. It may be ordered when a person (especially a person younger than age 40) has sudden bursts (paroxysms) of signs and symptoms such as:

  • High blood pressure (hypertension), especially when a person has hypertension that is not responding to treatment since people with catecholamine-secreting tumors are frequently resistant to standard therapies
  • Severe headaches
  • Sweating
  • Flushing
  • Rapid heart rate (palpitations)
  • Tremor

Testing may also be ordered when a catecholamine-secreting tumor has been treated or removed to monitor for recurrence.

Occasionally, the test may be ordered when an adrenal tumor is detected incidentally, such as during a scan conducted for another purpose, or when someone has a family history of pheochromocytomas. It may also be ordered on an asymptomatic person with a known genetic risk of these tumors.

What does the test result mean?

Normal urine levels of metanephrine and normetanephrine mean it is unlikely that the person tested has a catecholamine-secreting tumor. 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 in a person with signs and symptoms suggest the presence of a tumor. The person will receive appropriate follow up to confirm the finding. Guidelines also suggest that imaging tests, such as MRI, be performed to locate the probable tumor.

If levels are elevated in someone who has been treated for a catecholamine-secreting tumor, it may be an indication that the treatment was not fully effective or that the tumor is recurring and appropriate follow up is needed.

Is there anything else I should know?

While metanephrines testing can help detect and diagnose catecholamine-secreting tumors, it cannot tell the healthcare 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 genetic testing may be used to determine potential malignancy.

Although pheochromocytomas and extra-adrenal paragangliomas are rare, 25% 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.)

It has been proposed that all patients diagnosed with a pheochromocytoma or extra-adrenal paraganglioma should consider genetic counseling and testing. Early identification of a hereditary syndrome allows for early screening for other associated tumors. In addition, some people with a hereditary syndrome are more likely to develop malignant or recurrent disease. Knowledge of the specific genetic mutation permits increased vigilance during preoperative localization or postoperative surveillance of such patients.

It is also recommended that if a mutation is identified, predictive genetic testing should be offered to asymptomatic at-risk family members.

A variety of medications can interfere with catecholamines testing. However, it is important to talk to your healthcare provider before discontinuing any prescribed medications. The 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.

Tests used for determining the presence of catecholamine-secreting tumors (pheochromocytomas and paragangliomas) include plasma catecholamines, urine catecholamines, plasma free metanephrines and urine metanephrines. These tests measure either the catecholamines or their metabolites (metanephrines) and have varying sensitivity and specificity. Current guidelines recommend plasma free metanephrines or urinary fractionated metanephrines for initial biochemical testing. The healthcare provider may, however, select any one (or more than one) depending on the person's presentation, family history, and/or genetic profile.



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