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EPIC CODE: LAB2602 Metanephrines, Fractionated, Free, Plasma

Additional Codes

Sunquest:  METPM.
Mayo:         PMET

Reporting Name

Metanephrines, Fract., Free, P

Useful For

Screening test for presumptive diagnosis of catecholamine-secreting pheochromocytomas or paragangliomas

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Plasma EDTA

Specimen Required

Patient Preparation: Use of an Epi-pen within the last 7 days may produce inaccurate results.

Collection Container/Tube: Lavender top (EDTA)

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions: Centrifuge and aliquot plasma into a plastic vial within 2 hours of collection.

Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Plasma EDTA Frozen (preferred) 14 days
  Refrigerated  7 days

Reference Values


<0.50 nmol/L



<0.90 nmol/L

Day(s) Performed

Monday through Saturday

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


LOINC Code Information

Test ID Test Order Name Order LOINC Value
PMET Metanephrines, Fract., Free, P 57772-6


Result ID Test Result Name Result LOINC Value
10140 Normetanephrine, Free 40851-8
10139 Metanephrine, Free 49700-8

Clinical Information

Pheochromocytoma is a rare, though potentially lethal, tumor of chromaffin cells of the adrenal medulla that produces episodes of hypertension with palpitations, severe headaches, and sweating ("spells"). Patients with pheochromocytoma may also be asymptomatic and present with sustained hypertension or an incidentally discovered adrenal mass.


Pheochromocytomas and other tumors derived from neural crest cells (eg, paragangliomas and neuroblastomas) secrete catecholamines (epinephrine, norepinephrine, and dopamine). Metanephrine and normetanephrine (collectively referred to as metanephrines) are the 3-methoxy metabolites of epinephrine and norepinephrine, respectively. The metanephrines are stable metabolites and are cosecreted directly with catecholamines by pheochromocytomas and other neural crest tumors. This results in sustained elevations in plasma free metanephrine levels, making them more sensitive and specific than plasma catecholamines in the identification of pheochromocytoma patients.(1) Metanephrine and normetanephrine are both further metabolized to conjugated metanephrines and vanillylmandelic acid.


In the normal population, plasma metanephrine and normetanephrine levels are low, but in patients with pheochromocytoma or paragangliomas, the concentrations may be significantly elevated. This is due to the relatively long half-life of these compounds, ongoing secretion by the tumors and, to a lesser degree, peripheral conversion of tumor-secreted catecholamines into metanephrines.


Measurement of plasma free metanephrines appears to be the best test for excluding pheochromocytoma. The test's sensitivity approaches 100%, making it extremely unlikely that individuals with normal plasma metanephrine and normetanephrine levels suffer from pheochromocytoma or paraganglioma.(1,2)


Due to the low prevalence of pheochromocytomas and related tumors (<1:100,000), it is recommended to confirm elevated plasma free metanephrines with a second, different testing strategy in order to avoid large numbers of false-positive test results.(3) The recommended second-line test is measurement of fractionated 24-hour urinary metanephrines (METAF / Metanephrines, Fractionated, 24 Hour, Urine). In most cases this strategy will suffice in confirming or excluding the diagnosis. Occasionally, it will be necessary to extend this approach if there is a very high clinical index of suspicion or if test results are nonconclusive. In these cases, repeat plasma and urinary metanephrines testing, additional measurement of plasma or urinary catecholamines, or imaging procedures might be indicated.


Elevated results are reported with appropriate comments.


While most circulating metanephrines are derived directly from adrenal secretion, peripheral conversion of catecholamines makes a small contribution. Therefore, substances that increase endogenous catecholamine levels can result in borderline elevations of plasma metanephrines. These include:

-Monoamine oxidase inhibitors (MAOIs-a class of antidepressants with marked effects on catecholamine levels, particularly if the patient consumes tyrosine-rich foods such as nuts, bananas, or cheese)

-Catecholamine reuptake inhibitors including cocaine and synthetic cocaine derivatives such as many local anesthetics, some of which also are antiarrhythmic drugs (eg, lidocaine)

-Some anesthetic gases, particularly halothane

-Withdrawal from sedative drugs, medical or recreational, in particular alcohol, benzodiazepines (eg, Valium), opioids, and some central acting antihypertensive drugs, particularly clonidine, but, generally not cannabis or other hallucinogens such as lysergic acid diethylamide, mescal, or peyote


The observed elevations of plasma metanephrines are usually minor.


We are currently not aware of any substances that interfere directly with the assay.


Artifactually decreased plasma metanephrine levels may be observed when patients are already receiving metyrosine treatment. This drug may be administered in suspected or confirmed cases of pheochromocytoma while awaiting definitive treatment. It inhibits tyrosine hydroxylase, the enzyme that catalyzes the first step in catecholamine synthesis.

Supportive Data

This liquid chromatography/tandem mass spectrometry (LC-MS/MS) method replaces the in-house high-pressure liquid chromatography-electrochemical detection (HPLC-EC) method. The HPLC-EC method was labor intensive, with a complicated extraction and lengthy run time, and was prone to interferences. The LC-MS/MS method correlates well with Mayo Clinic Laboratories previously performed HPLC-EC method: N=92, slope=0.87, intercept=0.05, r(2)=0.95. The reference ranges remain the same as the HPLC-EC method and were validated by method comparison between these methods. LC-MS/MS also correlates with the National Institutes of Health's HPLC-EC method.

Clinical Reference

1. Eisenhofer G: Free or total metanephrines for diagnosis of pheochromocytoma: what is the difference? Clin Chem. 2001 Jun;47(6):988-989

2. Lenders JW, Pacek K, Walther MM, et al: Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002 Mar 20;287(11):1427-1434

3. Sawka AM, Jaeschke R, Singh RJ, Young WF Jr: A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared to the combination of 24-hour urinary metanephrines and catecholamines. J Clin Endocrinol Metab. 2003 Feb;88(2):553-558

4. Algeciras-Schimnich A, Preissner CM, Young WF Jr, et al: Plasma chromogranin A or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma fractionated metanephrines for pheochromocytoma. J Clin Endocrinol Metab.2008 Jan;93(1):91-95. doi: 10.1210/jc.2007-1354

Method Description

Free metanephrine and normetanephrine are extracted from plasma using solid phase extraction. The concentrated eluate is analyzed using liquid chromatography-tandem mass spectrometry and quantified using stable isotope-labeled internal standards, d3-metanephrine and d3-normetanephrine.(Taylor RL, Singh RJ: Validation of liquid chromatography-tandem mass spectrometry method for analysis of urinary conjugated metanephrine and normetanephrine for screening of pheochromocytoma. Clin Chem. 2002 Mar;48[3]:533-539)

Report Available

2 to 4 days

Specimen Retention Time

2 weeks

Reject Due To

Gross hemolysis Reject
Gross lipemia OK
Gross icterus OK

NY State Approved


Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)


If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-General Request (T239)

-Oncology Test Request (T729)