Test Catalog

Test Id : PMET

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Metanephrines, Fractionated, Free, Plasma

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Overview

Test Catalog

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)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Metanephrines, Fract., Free, P

Aliases
Lists additional common names for a test, as an aid in searching

Fractionated metanephrines +

Free Metanephrine

Metanephrines free, plasma

NMN (Normetanephrines), plasma

Normetanephrine, (NMN), free

Normetanephrines, plasma

Specimen Type
Describes the specimen type validated for testing

Plasma EDTA

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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.

Forms

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

-General Request (T239)

-Oncology Test Request (T729)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

0.3 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Plasma EDTA Frozen (preferred) 28 days
Refrigerated 14 days
Ambient 7 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

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 / 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:

-Monoamine oxidase inhibitors (MAOI-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, particularly 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-performance liquid chromatography with 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
Recommendations for 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;47(6):988-989

2. Lenders JW, Pacek K, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002;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;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;93(1):91-95. doi:10.1210/jc.2007-1354

5. Eisenhofer G, Deutschbein T, Constantinescu G, et al. Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma. Clin Chem Lab Med. 2020;59(2):353-363. doi:10.1515/cclm-2020-0904

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 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;48[3]:533-539)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Saturday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

2 weeks

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

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  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83835

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PMET Metanephrines, Fract., Free, P 57772-6
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
10140 Normetanephrine, Free 40851-8
10139 Metanephrine, Free 49700-8

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports