At a Glance

Why Get Tested?

To help diagnose or rule out a rare tumor of the adrenal gland called a pheochromocytoma or a rare tumor occurring outside the adrenal glands called a paraganglioma; these tumors (PPGL) produce excess hormones called catecholamines, which are broken down to metanephrines.

When To Get Tested?

When your healthcare provider either suspects that you have a tumor that produces catecholamines or wants to rule out the possibility; when you (especially if you are younger than age 40) have sudden bursts (paroxysms) of signs and symptoms, such as high blood pressure (especially if it doesn’t respond to standard treatment), severe headaches, rapid heart rate (palpitations), sweating, tremors and flushing; when you have a hereditary (genetic) risk for developing PPGL; when a tumor has been treated or removed, to monitor for recurrence; occasionally, when an adrenal tumor is detected by chance, such as during an imaging test for another condition

Sample Required?

A blood sample drawn from a vein

Test Preparation Needed?

Blood for plasma metanephrine testing is collected by inserting a needle into a vein in your arm. Although you may be seated for the collection, it is recommended that you be lying down. The health care practitioner or the collection site will instruct you as to their specific requirements.

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

What is being tested?

The metanephrines – metanephrine and normetanephrine – are breakdown products (metabolites) of the catecholamines epinephrine (adrenaline) and norepinephrine. The plasma free metanephrines test measures the amount of metanephrine and normetanephrine in the blood.

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, catecholamines are metabolized to 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 found in small fluctuating quantities in the blood and urine and only increase appreciably during and shortly after a stressful situation.

However, rare tumors of the adrenal glands called pheochromocytomas and rare tumors that occur outside the adrenal glands called paragangliomas can produce large amounts of the hormones, resulting in significantly 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 high blood pressure, which may lead to severe headaches. Other symptoms include 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, 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 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 catecholamine being produced and to eliminate their associated symptoms and complications.

How is the sample collected for testing?

Blood for plasma free metanephrines testing is collected by inserting a needle into a vein in the arm. Although you may be seated for the collection, it is recommended that you be lying down. Your healthcare practitioner or the collection site will instruct you as to their specific requirements.

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 any 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. Fasting may also be required prior to the sample being drawn.
  • 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.

Common Questions

How is it used?

The plasma free metanephrines test is used to help diagnose or rule out the presence of a rare tumor called a pheochromocytoma or a paraganglioma (PPGL) that releases excess metanephrines. Testing also may be used when a tumor has been treated or removed to monitor for recurrence.

The Endocrine Society, the American Association for Clinical Chemistry, and the European Society of Endocrinology have released clinical practice guidelines for the diagnosis and management of pheochromocytoma and paraganglioma. The guidelines recommend 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 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?

The plasma free metanephrines test is primarily ordered when your healthcare practitioner 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 you have hypertension that is not responding to treatment (people with these tumors are frequently resistant to standard therapies)
  • Severe headaches
  • Excessive sweating
  • Flushing
  • Rapid heart rate (palpitations)
  • Tremor

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 incidentally, such as during a scan conducted for another purpose, or when you have an inherited (genetic) risk or family history of pheochromocytomas.

What does the test result mean?

Normal metanephrine and normetanephrine blood levels mean it is unlikely that you have a tumor that produces catecholamines. The plasma free metanephrines test is very sensitive and these tumors are rare, making it the best test for excluding PPGL.

High levels of metanephrine and normetanephrine when you have signs and symptoms suggest the presence of a tumor. It is recommended that patients with a positive result receive appropriate follow-up according to the test values noted and the clinical presentation. Imaging scans, such as MRI, should be done to locate the tumor.

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. Sometimes the plasma free metanephrines test will be done along with 24-hour urine metanephrines testing and/or followed by catecholamines testing or imaging procedures to help decide if a catecholamine-secreting tumor is present.

Is there anything else I should know?

While the plasma free metanephrines test can help detect and diagnose the presence of a tumor that produces catecholamines, it cannot tell the healthcare provider the location of the tumor or whether it is benign or malignant (although most are benign). Imaging studies may be used to locate the tumor and genetic 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 von Hippel-Lindau [VHL] disease and multiple endocrine neoplasia type 2 [MEN2] syndrome. (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 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?

The level of catecholamines (and their metabolites) in blood is affected by diet. For test accuracy, interfering substances need to be avoided. Various foods, including caffeine-containing foods such as coffee and energy drinks, and chocolate, as well as cigarette and cigar smoking may interfere with the test and should be avoided prior to testing. It is important to follow the instructions given by your health care provider and the specimen collecting site.

Is it really necessary to lie down before testing?

You may be seated for the blood sample collection. However, recent guidelines suggest that it is preferable for the patient to be lying down. The healthcare provider or the collection site will instruct you as to their specific requirements.


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