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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 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
A 24-hour urine collection
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.
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 healthcare practitioner or the collection site or laboratory.
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.
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.
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:
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.
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.
While metanephrines testing can help detect and diagnose tumors that release catecholamines, it cannot tell your 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.)
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.
No, it has more to do with the characteristics of the tumor. Even a very small tumor can produce large amounts of catecholamines.
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.
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.