Test ID: PMET
Metanephrines, Fractionated, Free, Plasma
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Screening test for presumptive diagnosis of catecholamine-secreting pheochromocytomas or paragangliomas
Method Name A short description of the method used to perform the test
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Free Metanephrine
Metanephrines free, plasma
NMN (Normetanephrines), plasma
Normetanephrine, (NMN), free
Normetanephrines, plasma
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Collection Container/Tube: Lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Additional Information: If plasma catecholamines will be performed on this specimen, see CATP/8532 Catecholamine Fractionation, Plasma, Free for additional specimen requirements and restrictions.
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Moderate-reject if hemoglobin concentration is >250 mg/dL |
| Lipemia | Mild OK; Gross OK |
| Icterus | Mild OK; Gross OK |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Plasma EDTA | Frozen (preferred) | 14 days |
| Refrigerated | 7 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
METANEPHRINE, FREE
<0.50 nmol/L
NORMETANEPHRINE, FREE
<0.90 nmol/L
Interpretation Provides information to assist in interpretation of the test results
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/83006 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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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:
-Monamine oxidase inhibitors (MOIs-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 (LSD), mescal, or peyote
The observed elevations of plasma metanephrines are usually minor.
We are currently not aware of any substances that interfere directly in 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 Medical 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 Provides recommendations for further in-depth reading of a clinical nature
1. Eisenhofer G: Free or total metanephrines for diagnosis of pheochromocytoma: what is the difference? Clin Chem 2001 June;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 Oct 16, 2007;doi:doi:10.1210/jc.2007-1354
Method Description Describes how the test is performed and provides a method-specific reference
Free metanephrine and normetanephrine are extracted from plasma using solid phase extraction. The concentrated eluate is analyzed using liquid chromatography-tandem mass spectometry (LC-MS/MS) and quantified using stable isotope labeled internal standards, d(3)-metanephrine and d(3)-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)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Saturday; 1 p.m.- Not Reported on Sunday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83835
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 10140 | Normetanephrine, Free | 40851-8 |
| 10139 | Metanephrine, Free | 49700-8 |
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