Also Known As
Metanephrines
Normetanephrine
Fractionated Metanephrines
Free Metanephrines, urine
Formal Name
Urine Metanephrines, Total and Fractionated
This article was last reviewed on
This article waslast modified on July 19, 2019.
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 outside the adrenal glands called a paraganglioma; these tumors (PPGL) produce excess 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 incidentally, such as during an imaging test

Sample Required?
Test Preparation Needed?

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.

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?

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 healthcare practitioner or the collection site or laboratory.

  • You should talk to your healthcare 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 healthcare 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.
Accordion Title
Common Questions
  • 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 healthcare 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 healthcare 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 (hypertension), especially when your hypertension is not responding to treatment (people with these tumors are frequently resistant to standard therapies)
    • Severe headaches
    • 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 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 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 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.

View Sources

Sources Used in Current Review

2019 Review performed by Stanley S. Levinson, PhD, DABCC.

(August 10, 2018) Blake, M. Medscape: pheochromocytoma. Available online at https://emedicine.medscape.com/article/124059. Accessed July 2019.

Samuels M, et al. Case 14-2010: A 54-year old women with dizziness and falls. N Engl J Med 362, 2010, pages 1815-23.

Loscalzo J, et al. Case 8-2018: A 55-year old woman with shock and labile blood pressure. N Engl J Med 378, 2018, pages 1043-1053.

Alzrek R, et al. Update of Pheochromocytoma Syndromes: Genetics, Biochemical Evaluation, and Imaging. Front Endocrinol (Lausanne). 2018; 9: 515. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277481/. Accessed July 2019.

Sources Used in 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.

Sawka, A., et. al. (2003 February). A Comparison of Biochemical Tests for Pheochromocytoma: Measurement of Fractionated Plasma Metanephrines Compared with the Combination of 24-Hour Urinary Metanephrines and Catecholamines. The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 2 553-558 [On-line journal]. Available online at http://jcem.endojournals.org/cgi/content/full/88/2/553.

Brose, M. Updated (2004 August 3, Updated). Pheochromocytoma. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000340.htm.

(© 2005). 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.

(© 2005). Metanephrines, Urine. ARUP's Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.aruplab.com/guides/clt/tests/clt_a77b.jsp#1141889.

(© 1995-2005). Pheochromocytoma. The Merck Manual of Diagnosis and Therapy, Section 2. Endocrine And Metabolic Disorders, Chapter 9. Adrenal Disorders [On-line information]. Available online at http://www.merck.com/mrkshared/mmanual/section2/chapter9/9d.jsp.

Vogin, G. Reviewed (2002). Plasma Metanephrines Best to Diagnose Pheochromocytoma. Medscape Medical News [On-line news article]. Available online at http://www.medscape.com/viewarticle/430266?src=search.

Schwartz, G. and Sheps, S. (2004 May 06). Hypertension. MedScape Today from ACP Medicine [On-line information]. Available online at http://www.medscape.com/viewarticle/474790?src=search.

(1998 May 27, Updated). Adrenal Medullary Hormones. Colorado State University, Hypertexts for Biological Sciences [On-line hypertextbook]. Available online at http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/adrenal/medhormones.html.

Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference. 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 987-990.

Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry. AACC Press, Washington, DC. Pp 382-383.

Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 724-731.

Pacak, K. et. al. (2007 March 21). Pheochromocytoma: Recommendations for Clinical Practice from the First International Symposium. Medscape from Nat Clin Pract Endocrinol Metab. 2007;3(2):92-102. [On-line information]. Available online at http://www.medscape.com/viewarticle/553428. Accessed on 9/29/08.

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 9/29/08.

Vilar, L. (2008 June 17). Adrenal Incidentalomas: Diagnostic Evaluation and Long-Term Follow-up. Medscape from Endocr Pract. 2008;14(3):269-278 [On-line information]. Available online at http://www.medscape.com/viewarticle/574415. Accessed on 9/29/08.

(2007 December). Pheochromocytoma. UrologyHealth.org [On-line information]. Available online at http://urologyhealth.org/adult/index.cfm?cat=02&topic=114. Accessed on 9/29/08.

Grossman, A. (2007 November Reviewed). Pheochromocytoma. Merck Manual for Professionals [On-line information]. Available online at http://www.merck.com/mmpe/print/sec12/ch153/ch153h.html. Accessed on 9/29/08.

Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 1023-1026.

(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.

(© 1995-2011). Test ID: METAR83005, Metanephrines, Fractionated, Random, Urine. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/83005. 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.

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, 24 Hour, Urine. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/83006. 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 973-976.

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.

Ask a Laboratory Scientist

This form enables you to ask specific questions about lab tests. Your questions will be answered by a laboratory scientist as part of a voluntary service provided by one of our partners, American Society for Clinical Laboratory Science. Please allow 2-3 business days for an email response from one of the volunteers. 

Country
Disclaimer
Thank you for using the Consumer Information Response Service ("the Service") to inquire about the meaning of your lab test results.  The Service is provided free of charge by the American Society for Clinical Laboratory Science, which is one of many laboratory organizations that supports Lab Tests Online.
Please note that information provided through this free Service is not intended to be medical advice and should not be relied on as such. Although the laboratory provides the largest single source of objective, scientific data on patient status, it is only one part of a complex biological picture of health or disease. As professional clinical laboratory scientists, our goal is to assist you in understanding the purpose of laboratory tests and the general meaning of your laboratory results. It is important that you communicate with your physician so that together you can integrate the pertinent information, such as age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), to determine your health status. The information provided through this Service is not intended to substitute for such consultations with your physician nor specific medical advice to your health condition.
By submitting your question to this Service, you agree to waive, release, and hold harmless the American Society for Clinical Laboratory Science and its affiliates or their past or present officers, directors, employees, agents, and Service volunteers (collectively referred to as "ASCLS") and the American Association  for Clinical Chemistry and its affiliates or their past or present officers, directors, employees, agents, and Service volunteers (collectively referred to as "AACC") from any legal claims, rights, or causes of action you may have in connection with the responses provided to the questions that you submit to the Service.
AACC, ASCLS and its Service volunteers disclaim any liability arising out of your use of this Service or for any adverse outcome from your use of the information provided by this Service for any reason, including but not limited to any misunderstanding or misinterpretation of the information provided through this Service.