Test Catalog

Test Id : METAF

Metanephrines, Fractionated, 24 Hour, Urine

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

A first- and second-order screening test for the presumptive diagnosis of catecholamine-secreting pheochromocytomas and paragangliomas

 

Confirming positive plasma metanephrine results

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Stable Isotope Dilution Analysis

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, Fractionated, 24h, U

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

Free Metanephrine

Metanephrines free, urine

NMN (Normetanephrines), urine

Normetanephrine, (NMN), free

Normetanephrines, urine

Fractionated metanephrines

Specimen Type
Describes the specimen type validated for testing

Urine

Necessary Information

24-Hour volume is required.

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

Patient Preparation: Tricyclic antidepressants, labetalol, and sotalol medications may elevate levels of metanephrines producing results that cannot be interpreted. If clinically feasible, it is optimal to discontinue these medications at least 1 week before collection. For advice on assessing the risk of removing patients from these medications and alternatives, consider consultation with a specialist in endocrinology or hypertension.

Supplies: Urine Tubes, 10 mL (T068)

Container/Tube: Plastic urine tube

Specimen Volume: 10 mL

Collection Instructions:

1. Collect urine for 24 hours.

2. Add 10 g (pediatric: 3 g) of boric acid or 25 mL (pediatric: 15 mL) of 50% acetic acid as preservative at start of collection.

Additional Information: See Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens for multiple collections.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

Urine Preservative Collection Options

Note: The addition of preservative must occur prior to the start of the collection or application of temperature controls must occur during collection.

Ambient

No

Refrigerate

OK

Frozen

OK

50% Acetic Acid

Preferred

Boric Acid

Preferred

Diazolidinyl Urea

No

6M Hydrochloric Acid

OK

6M Nitric Acid

OK

Sodium Carbonate

OK

Thymol

No

Toluene

OK

 

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

3 mL

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

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

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
Urine Refrigerated (preferred) 28 days
Ambient 28 days
Frozen 28 days

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

A first- and second-order screening test for the presumptive diagnosis of catecholamine-secreting pheochromocytomas and paragangliomas

 

Confirming positive plasma metanephrine results

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 are the 3-methoxy metabolites of epinephrine and norepinephrine, respectively. Metanephrine and normetanephrine are both further metabolized to vanillylmandelic acid.

 

Pheochromocytoma cells also have the ability to oxymethylate catecholamines into metanephrines that are secreted into circulation.

 

In patients that are highly suspect for pheochromocytoma, it may be best to screen by measuring plasma free fractionated metanephrines (a more sensitive assay). The 24-hour urinary fractionated metanephrines (a more specific assay) may be used as the first test for low suspicion cases and also as a confirmatory study in patients with a less than 2-fold elevation in plasma free fractionated metanephrines. This is highly desirable, as the very low population incidence rate of pheochromocytoma (<1:100,000 population per year) will otherwise result in large numbers of unnecessary, costly, and sometimes risky imaging procedures.

 

Complete 24-hour urine collections are preferred, especially for patients with episodic hypertension; ideally the collection should begin at the onset of a spell.

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

Males

Normotensives

3-8 years: 29-92 mcg/24 hours

9-12 years: 59-188 mcg/24 hours

13-17 years: 69-221 mcg/24 hours

> or =18 years: 44-261 mcg/24 hours

Reference values have not been established for patients that are younger than 36 months of age.

 

Hypertensives: <400 mcg/24 hours

Females

Normotensives

3-8 years: 18-144 mcg/24 hours

9-12 years: 43-122 mcg/24 hours

13-17 years: 33-185 mcg/24 hours

> or =18 years: 30-180 mcg/24 hours

Reference values have not been established for patients that are younger than 36 months of age.

 

Hypertensives: <400 mcg/24 hours

 

NORMETANEPHRINE

Males

Normotensives

3-8 years: 34-169 mcg/24 hours

9-12 years: 84-422 mcg/24 hours

13-17 years: 91-456 mcg/24 hours

18-29 years: 103-390 mcg/24 hours

30-39 years: 111-419 mcg/24 hours

40-49 years: 119-451 mcg/24 hours

50-59 years: 128-484 mcg/24 hours

60-69 years: 138-521 mcg/24 hours

> or =70 years: 148-560 mcg/24 hours

Reference values have not been established for patients that are younger than 36 months of age.

 

Hypertensives: <900 mcg/24 hours

 

Females

Normotensives

3-8 years: 29-145 mcg/24 hours

9-12 years: 55-277 mcg/24 hours

13-17 years: 57-286 mcg/24 hours

18-29 years: 103-390 mcg/24 hours

30-39 years: 111-419 mcg/24 hours

40-49 years: 119-451 mcg/24 hours

50-59 years: 128-484 mcg/24 hours

60-69 years: 138-521 mcg/24 hours

> or =70 years: 148-560 mcg/24 hours

Reference values have not been established for patients that are younger than 36 months of age.

 

Hypertensives: <900 mcg/24 hours

 

TOTAL METANEPHRINE

Males

Normotensives

3-8 years: 47-223 mcg/24 hours

9-12 years: 201-528 mcg/24 hours

13-17 years: 120-603 mcg/24 hours

18-29 years: 190-583 mcg/24 hours

30-39 years: 200-614 mcg/24 hours

40-49 years: 211-646 mcg/24 hours

50-59 years: 222-680 mcg/24 hours

60-69 years: 233-716 mcg/24 hours

> or =70 years: 246-753 mcg/24 hours

Reference values have not been established for patients that are younger than 36 months of age.

 

Hypertensives: <1,300 mcg/24 hours

 

Females

Normotensives

3-8 years: 57-210 mcg/24 hours

9-12 years: 107-394 mcg/24 hours

13-17 years: 113-414 mcg/24 hours

18-29 years: 142-510 mcg/24 hours

30-39 years: 149-535 mcg/24 hours

40-49 years: 156-561 mcg/24 hours

50-59 years: 164-588 mcg/24 hours

60-69 years: 171-616 mcg/24 hours

> or =70 years: 180-646 mcg/24 hours

Reference values have not been established for patients that are younger than 36 months of age.

 

Hypertensives: <1,300 mcg/24 hours

 

For SI unit Reference Values, see www.mayocliniclabs.com/order-tests/si-unit-conversion.html

Interpretation
Provides information to assist in interpretation of the test results

Increased metanephrine and normetanephrine levels are found in patients with pheochromocytoma and tumors derived from neural crest cells.

 

Total urine metanephrine levels of 1300 mcg/24 hours and lower can be detected in non-pheochromocytoma hypertensive patients.

 

Further clinical investigation (eg, radiographic studies) is warranted in patients whose total urinary metanephrine levels are above 1300 mcg/24 hours (approximately 2 times the upper limit of normal). For patients with total urinary metanephrine levels below 1300 mcg/24 hours, further investigations may also be indicated if either the normetanephrine or the metanephrine fraction of the total metanephrines exceed their respective upper limit for hypertensive patients. Finally, repeat testing or further investigations may occasionally be indicated in patients with urinary metanephrine levels below the hypertensive cutoff, or even normal levels, if there is a very high clinical index of suspicion.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test utilizes a liquid chromatography/tandem mass spectrometry method and is not affected by the interfering substances that affected the previously utilized spectrophotometric (Pisano reaction) method (ie, diatrizoate, chlorpromazine, hydrazine derivatives, imipramine, monamine oxidase [MAO] inhibitors, methyldopa, phenacetin, ephedrine, or epinephrine).

 

This method is not subject to the known interference of acetaminophen (seen with the plasma metanephrine high performance liquid chromatography-electrochemical method).

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. van Duinen N, Corssmit EPM, de Jong WHA, Brookman D, Kema IP, Romijn JA: Plasma levels of free metanephrines and 3-methoxytyramine indicate a higher number of biochemically active HNPGL than 24-h urinary excretion rates of catecholamines and metabolites. Eur J Endocrinol. 2013 Aug 28;169(3):377-382. doi: 10.1530/EJE-13-0529

2. Pacak K, Linehan WM, Eisenhofer G, Walther MM, Goldstein DS: Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med. 2001 Feb 20;134(4):315-329

3. Sawka AM, Singh RJ, Young WF Jr: False positive biochemical testing for pheochromocytoma caused by surreptitious catecholamine addition to urine. Endocrinologist. 2001;11:421-423

4. Eisenhofer G, Grebe S, Cheung NKV: Monoamine-producing tumors. In: Rafai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:1421

5. Shen Y, Cheng L: Biochemical diagnosis of pheochromocytoma and paraganglioma. In: Mariani-Costantini R, ed. Paraganglioma: A Multidisciplinary Approach. Codon Publications; 2019. doi: 10.15586/paraganglioma.2019.ch2. Accessed: April 2020. Available at: www.ncbi.nlm.nih.gov/books/NBK543224/

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Urinary metanephrines are determined by reverse phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) stable isotope dilution analysis. Urinary metanephrines occur largely in conjugated form. After urine specimens are acidified and hydrolyzed for 20 minutes in a boiling water bath, metanephrine and normetanephrine are extracted from the specimens utilizing extraction cartridges. The metanephrine and normetanephrine are eluted from the cartridge using 20% methanol (MeOH) and analyzed by LC-MS/MS using multiple reaction monitoring in positive mode. Deuterated metanephrine (d3-metanephrine, 200 ng) and deuterated normetanephrine (d3-normetanephrine, 500 ng) are added prior to the hydrolysis as an internal standard. The following ion pairs are used for analysis: metanephrine, (180/148); normetanephrine, (166/134); d3-metanephrine, (183/151); d3-normetanephrine, (169/137). The metanephrine and normetanephrine concentrations are quantified using ratios of the peak areas to deuterium-labeled internal standards by LC-MS/MS. A calibration curve, generated from 20% MeOH spiked standards, is included with each batch of patient specimens.(Taylor RL, Singh RJ: Validation of liquid chromatography-tandem mass spectometry method for analysis of urinary conjugated metanephrine and normetanephrine for screening of pheochromocytoma. Clin Chem. 2002 Mar;48(3):533-539; Roden M, Raffesberg W, Raber W, et al: Quantification of unconjugated metanephrine in human plasma without interference by acetaminophen. Clin Chem. 2001 Jun;47(6):1061-1067)

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 Friday

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.

3 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.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. 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. This test 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
METAF Metanephrines, Fractionated, 24h, U In Process
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.
8552 Metanephrine, U 19049-6
21545 Normetanephrine, U 2671-6
83006 Total Metanephrines, U 2609-6
TM50 Collection Duration 13362-9
VL48 Urine Volume 3167-4
2434 Comment 48767-8

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 | Create a 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