Also Known As
Plasma Metanephrines
Formal Name
Fractionated Plasma Free Metanephrines (Metanephrine and Normetanephrine)
This article was last reviewed on
This article waslast modified on
May 28, 2018.
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 symptoms of increased catecholamines release such as sudden bursts (paroxysms) of high blood pressure (hypertension), severe headaches, rapid heart rate (palpitations), sweating, and tremors; when hypertension does not respond to standard treatment; 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 a health practitioner suspects you may have a tumor that is releasing or may release excess catecholamines

Sample Required?

A blood sample drawn from a vein in your arm

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 healthcare provider 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 provider of any medications you are taking and follow any preparation instructions you are given before sample collection.

You may be able to find your test results on your laboratory's website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab's website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called "normal" values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

The metanephrines - metanephrine and normetanephrine - are breakdown products (metabolites) of epinephrine (adrenaline) and norepinephrine. Epinephrine and norepinephrine belong to a group of similar hormones called catecholamines. The plasma free metanephrines test measures the amount of metanephrine and normetanephrine in the blood.

Catecholamines are produced in the adrenal medulla, the interior 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 bloodstream 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 metabolites 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 adrenal tumors called pheochromocytomas and rare extra-adrenal tumors called paragangliomas can produce large amounts of the hormones, resulting in significantly 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 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.

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 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 the patient may be seated for the collection, it is recommended that the patient be lying down. The healthcare provider or the collection site will instruct the patient 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 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 person will also be instructed on what foods to avoid. Fasting may also be required prior to the sample being drawn.
  • Emotional and physical stresses and vigorous exercise should be minimized prior to and during sample collection as they can increase catecholamine release and therefore affect metanephrine levels.
Accordion Title
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 that releases excess metanephrines. Testing also may be used when a tumor has been treated or removed to monitor for recurrence.

    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 plasma free metanephrines test will done in conjunction with 24-hour urine metanephrines testing and/or followed by catecholamines testing to help decide if a catecholamine-secreting tumor is present.

  • When is it ordered?

    The plasma free metanephrines test is primarily ordered when a health practitioner 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 conventional 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 strong personal or family history of catecholamine-secreting tumors. It may also be ordered for an asymptomatic person with a known genetic risk of these tumors.

  • What does the test result mean?

    Normal metanephrine and normetanephrine blood levels mean it is unlikely that the person tested has a catecholamine-secreting tumor. The plasma free metanephrines test is very sensitive and these tumors are rare, so the negative predictive value of the test is very good.

    High levels of metanephrine and normetanephrine in a person with signs and symptoms suggest the presence of a catecholamine-secreting tumor. It is recommended that patients with a positive result should 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 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 the plasma free metanephrines test can help detect and diagnose the presence of a catecholamine-secreting tumor, 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.

    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 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.

  • 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. A person 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 healthcare provider and the specimen collecting site.

  • Is it really necessary to lie down before testing?

    The patient 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 the patient as to their specific requirements.

View Sources

Sources Used in Current Review

Blake, M. and Sweeney, A. (2014 June 16, Updated). Pheochromocytoma. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/124059-overview. Accessed on 4/25/15.

Vuguin, P. (2013 June 27 Updated). Pediatric Pheochromocytoma. Medscape Drugs & Diseases [On-line information]. Available online at http://emedicine.medscape.com/article/988683-overview. Accessed 04/25/15.

Baldwin, E. et. al. (2015 April, Updated). Pheochromocytoma. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Pheochromocytoma.html?client_ID=LTD. Accessed 4/25/15.

(© 1995–2015). Metanephrines, Fractionated, Free, Plasma. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/81609. Accessed 04/25/15.

(2015 April 10, Updated). Unusual Cancers of Childhood Treatment (PDQ®). National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/cancertopics/pdq/treatment/unusual-cancers-childhood/Patient/page7. Accessed 04/25/15.

Pagana, K. D., Pagana, T. J., and Pagana, T. N. (© 2015). Mosby's Diagnostic & Laboratory Test Reference 12th Edition: Mosby, Inc., Saint Louis, MO. Pp 636-637.

National Cancer Institute: PDQ® Pheochromocytoma and Paraganglioma Treatment. Bethesda, MD: National Cancer Institute. Date last modified 04/30/2015. Available online at http://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq. Accessed 07/21/2105.

Lenders, J.W.M. et al. Guidelines on Pheochromocytoma and Paraganglioma. J Clin Endocrinol Metab, June 2014, 99(6): 1915-42

Eisenhofer, G. and Peitzch, M. Laboratory Evaluation of Pheochromocytoma and Paraganglioma. Clinical Chemistry, 2014, 60(12) 1486–1499.

Sources Used for Previous Reviews

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. Pp (900-903).

(© 2004). Metanephrines, Plasma. ARUP's Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.aruplab.com/guides/clt/tests/clt_a76b.jsp#2461156.

(© 2004). Metanephrines, Plasma. ARUP's User's Guide [On-line test information]. Available online at http://www.aruplab.com/guides/ug/tests/0050184.jsp.

Eisenhofer, G. et. al. (© 2003). Biochemical Diagnosis of Pheochromocytoma: How to Distinguish True- from False-Positive Test Results. The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 6 2656-2666 [On-line journal]. Available online at http://jcem.endojournals.org/cgi/content/full/88/6/2656.

Yogish, C. (2003 October). The Laboratory Diagnosis of Adrenal Pheochromocytoma: The Mayo Clinic Experience. The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 10 4533-4539 [On-line journal]. Available online at http://jcem.endojournals.org/cgi/content/full/88/10/4533.

(1999 June 16). Researchers Develop Better Means to Diagnose Adrenal Gland Tumors. NIH News Release [On-line press release]. Available online at http://www.nih.gov/news/pr/jun99/ninds-16.htm.

Sadovsky, R. (2003 September 15). Management of the Clinically Inapparent Adrenal Mass. American Family Physician, Tips from Other Journals [On-line journal]. Available online at http://www.aafp.org/afp/20030915/tips/9.html.

(2003 December 18). Pheochromocytoma (PDQ®): Treatment, Health Professional Version. National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/cancertopics/pdq/treatment/pheochromocytoma/HealthProfessional.

Howard, S. (2002 August 29). heochromocytoma. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000340.htm.

(2002 September). Pheochromocytoma. NIH, Warren Grant Magnuson Clinical Center, Patient Information Publications [On-line information]. PDF available for download at http://www.cc.nih.gov/ccc/patient_education/pepubs/pheo.pdf.

Schwartz, G. and Sheps, S. (2004 May 6). Hypertension. Medscape from ACP Medicine 2004. © 2004 WebMD Inc. [On-line article]. Available online at http://www.medscape.com/viewarticle/474790.

(© 2004). Pheochromocytoma. The Merck Manual Second Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/sec13/ch164/ch164f.html.

Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 728-279.

(2008 June 18, Modified). Pheochromocytoma Treatment, Patient Version. National Cancer Institute [On-line information]. Available online at http://www.cancer.gov/cancertopics/pdq/treatment/pheochromocytoma/patient/allpages. Accessed on 7-28-08.

(2007 April 17, Updated). Pheochromocytoma. National Institute of Child Health and Human Development [On-line information]. Available online at http://www.nichd.nih.gov/health/topics/pheochromocytoma.cfm. Accessed on 7-27-08.

Nanda, R. (2006 September 11, Update). Pheochromocytoma. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000340.htm. Accessed on 7-28-08.

Sweeney, A. et. al. (2007 September 11, Updated). Pheochromocytoma. eMedicine [On-line information]. Available online at http://www.emedicine.com/med/TOPIC1816.HTM. Accessed on 7-28-08.

(© 2006-2008). Pheochromocytoma. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/OncologicDz/NeuroendocrineTumors/Pheochromocytoma.html. Accessed on 7-28-08.

Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 673-675.

Vuguin, P. M. (Updated 2011 October 4). Pediatric Pheochromocytoma. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/988683-overview. Accessed December 2011.

(Reviewed 2011 January). Pheochromocytoma. American Urological Association AUA Foundation [On-line information]. Available online at http://www.urologyhealth.org/urology/index.cfm?article=14. Accessed December 2011.

Blake, M. and Sweeney, A. (Updated 2011 October 19). Pheochromocytoma. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/124059-overview. Accessed December 2011.

Frank, E. et. al. (Updated 2011 June). Pheochromocytoma. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Pheochromocytoma.html?client_ID=LTD. Accessed December 2011.

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