Useful For
Suggests clinical disorders or settings where the test may be helpful
A second-order screening test for the presumptive diagnosis of pheochromocytoma in patients with non-episodic hypertension
Confirming positive plasma metanephrine results in patients with non-episodic hypertension
Test Id |
Reporting Name |
Available Separately |
Always Performed |
METAU |
Metanephrines, Fractionated, U |
No
|
Yes |
CRETR |
Creatinine, Random, U |
Yes, (Order RCTUR)
|
Yes |
Method Name
A short description of the method used to perform the test
METAU: Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
CRETR: Enzymatic Colorimetric Assay
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., Random, U
Aliases
Lists additional common names for a test, as an aid in searching
Fractionated metanephrines
Metanephrines free, urine
NMN (Normetanephrines), urine
Normetanephrine, (NMN), free
Normetanephrines, urine
METAR
METAU
METRN
Specimen Type
Describes the specimen type validated for testing
Urine
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Patient Preparation:
1. For at least 48 hours prior to test, patient should avoid use of cold medicines, nose drops, and nasal sprays.
2. Patients taking tricyclic antidepressants and labetalol and sotalol (beta blockers) may have falsely elevated levels of metanephrines. If medically feasible, for at least 1 week before specimen collection, the patient should not take these medications.
Supplies: Urine Tubes, 10 mL (T068)
Collection Container/Tube: Clean, plastic urine collection container
Submission Container/Tube: Plastic, 10 mL urine tube
Specimen Volume: 10 mL
Collection Instructions:
1. Collect a random urine specimen.
2. No preservative.
Forms
If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.
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.
3 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
Thawing Cold OK; Warm OK
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.
Specimen Type |
Temperature |
Time |
Special Container |
Urine |
Ambient |
14 days |
|
|
Refrigerated (preferred) |
28 days |
|
|
Frozen |
28 days |
|
Useful For
Suggests clinical disorders or settings where the test may be helpful
A second-order screening test for the presumptive diagnosis of pheochromocytoma in patients with non-episodic hypertension
Confirming positive plasma metanephrine results in patients with non-episodic hypertension
Pheochromocytoma is a rare, potentially lethal, tumor of chromaffin cells of the adrenal medulla that produces episodes of hypertension with palpitations, severe headaches, and sweating ("spells").
Pheochromocytomas and other tumors derived from neural crest cells (eg, paragangliomas and neuroblastomas) secrete catecholamines (epinephrine and norepinephrine).
Metanephrine and normetanephrine are the 3-methoxy metabolites of epinephrine and norepinephrine, respectively. Both are further metabolized to vanillylmandelic acid.
Pheochromocytoma cells are also able to oxymethylate catecholamines into metanephrines that are secreted into circulation.
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/CREATININE
Normotensives
0-2 years: 82-418 mcg/g creatinine
3-8 years: 65-332 mcg/g creatinine
9-12 years: 41-209 mcg/g creatinine
13-17 years: 30-154 mcg/g creatinine
> or =18 years: 29-158 mcg/g creatinine
NORMETANEPHRINE/CREATININE
Males
Normotensives
0-2 years: 121-946 mcg/g creatinine
3-8 years: 92-718 mcg/g creatinine
9-12 years: 53-413 mcg/g creatinine
13-17 years: 37-286 mcg/g creatinine
18-29 years: 53-190 mcg/g creatinine
30-39 years: 60-216 mcg/g creatinine
40-49 years: 69-247 mcg/g creatinine
50-59 years: 78-282 mcg/g creatinine
60-69 years: 89-322 mcg/g creatinine
> or =70 years: 102-367 mcg/g creatinine
Females
Normotensives
0-2 years: 121-946 mcg/g creatinine
3-8 years: 92-718 mcg/g creatinine
9-12 years: 53-413 mcg/g creatinine
13-17 years: 37-286 mcg/g creatinine
18-29 years: 81-330 mcg/g creatinine
30-39 years: 93-379 mcg/g creatinine
40-49 years: 107-436 mcg/g creatinine
50-59 years: 122-500 mcg/g creatinine
60-69 years: 141-574 mcg/g creatinine
> or =70 years: 161-659 mcg/g creatinine
TOTAL METANEPHRINE/CREATININE
Males
Normotensives
0-2 years: 241-1,272 mcg/g creatinine
3-8 years: 186-980 mcg/g creatinine
9-12 years: 110-582 mcg/g creatinine
13-17 years: 78-412 mcg/g creatinine
18-29 years: 96-286 mcg/g creatinine
30-39 years: 106-316 mcg/g creatinine
40-49 years: 117-349 mcg/g creatinine
50-59 years: 130-386 mcg/g creatinine
60-69 years: 143-427 mcg/g creatinine
> or =70 years: 159-472 mcg/g creatinine
Females
Normotensives
0-2 years: 241-1,272 mcg/g creatinine
3-8 years: 186-980 mcg/g creatinine
9-12 years: 110-582 mcg/g creatinine
13-17 years: 78-412 mcg/g creatinine
18-29 years: 131-467 mcg/g creatinine
30-39 years: 147-523 mcg/g creatinine
40-49 years: 164-585 mcg/g creatinine
50-59 years: 184-655 mcg/g creatinine
60-69 years: 206-733 mcg/g creatinine
> or =70 years: 230-821 mcg/g creatinine
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.
Increased urine metanephrines can be detected in non-pheochromocytoma hypertensive patients; quantification may help distinguish these patients from those with tumor-induced symptoms.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
While screening for pheochromocytoma is best accomplished by measuring free fractionated metanephrines in plasma (a more sensitive assay), follow-up testing with urinary fractionated metanephrines (a more specific assay) may identify false-positive results. Twenty-four-hour urine collections are preferred, especially for patients with episodic hypertension; ideally the collection should begin at the onset of a "spell."
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, monoamine oxidase inhibitors [MAOI], methyldopa, phenacetin, ephedrine, or epinephrine).
This method is also not subject to the known interference of acetaminophen, which is seen with the plasma metanephrine test using high-performance liquid chromatography with electrochemical detection.
When N-acetylcysteine is administered at levels sufficient to act as an antidote for the treatment of acetaminophen overdose, it may lead to falsely decreased creatinine results.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. van Duinen N, Corssmit EPM, de Jong WHA, Brookman D, Kema P, 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;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;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: Rifai 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. Accessed May 2, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK543224/
6. Hernandez FC, Sanchez M, Alvarez A, et al. A five-year report on experience in the detection of pheochromocytoma. Clin Biochem. 2000;33(8):649-55. doi:10.1016/s0009-9120(00)00172-7
7. van Duinen N, Steenvoorden D, Kema IP, et al. Increased urinary excretion of 3-methoxytyramine in patients with head and neck paragangliomas. J Clin Endocrinol Metab. 2010;95(1):209-14. doi:10.1210/jc.2009-1632
8. Le Jacques A, Abalain JH, Le Saos F, Carre JL. Significance of 3-methoxytyramine urine measurement in the diagnosis of pheochromocytomas and paragangliomas: about 28 patients. Ann Biol Clin (Paris). 2011;69(5):555-9. French. doi:10.1684/abc.2011.0612
9. Muskiet FA, Thomasson CG, Gerding AM, Fremouw-Ottevangers DC, Nagel GT, Wolthers BG. Determination of catecholamines and their 3-O-methylated metabolites in urine by mass fragmentography with use of deuterated internal standards. Clin Chem. 1979;25(3):453-60
10. Hirsch D, Grossman A, Nadler V, Alboim S, Tsvetov G. Pheochromocytoma: Positive predictive values of mildly elevated urinary fractionated metanephrines in a large cohort of community-dwelling patients. J Clin Hypertens (Greenwich). 2019;21(10):1527-1533. doi:10.1111/jch.13657
Method Description
Describes how the test is performed and provides a method-specific reference
Urinary metanephrines are determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urinary metanephrines occur largely in conjugated form. After urine samples are acidified and hydrolyzed in a heat block, metanephrine and normetanephrine are extracted from the specimens utilizing extraction cartridges. The metanephrine, normetanephrine, and 3-methoxytyramine (3MT) are eluted from the cartridge and analyzed by LC/MS/MS using multiple reaction monitoring in positive mode. Deuterated metanephrine (d3-metanephrine), deuterated normetanephrine (d3-normetanephrine), and deuterated 3MT (d4-3MT) are added prior to the hydrolysis as internal standards. The metanephrine, normetanephrine, and 3-MT concentrations are quantified using ratios of the peak areas to deuterium labeled internal standards by LC-MS/MS.(Unpublished Mayo method)
Creatinine:
The enzymatic method is based on the determination of sarcosine from creatinine with the aid of creatininase, creatinase, and sarcosine oxidase. The liberated hydrogen peroxide is measured via a modified Trinder reaction using a colorimetric indicator. Optimization of the buffer system and the colorimetric indicator enables the creatinine concentration to be quantified both precisely and specifically.(Package insert: Creatinine plus ver 2. Roche Diagnostics; V15.0, 03/2019)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
No
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
Rochester
Fees :
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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.
83835
82570
Test Id |
Test Order Name |
Order LOINC Value
|
METRN |
Metanephrines, Fract., Random, U |
68317-7 |
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.
|
21546 |
Metanephrine/Creatinine |
9645-3 |
21547 |
Normetanephrine/Creatinine |
13783-6 |
21548 |
Total Metanephrine/Creatinine |
13771-1 |
CRETR |
Creatinine, Random, U |
2161-8 |