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Epic Code LAB1230839 Metanephrines, Fractionated, Random, Urine

Additional Codes

Mayo Code: METRN

Interface Code: 1230839

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Useful For

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

Specimen Type

Urine


Specimen Required


Patient Preparation: Patient should refrain from cold medicines, nose drops, and nasal sprays for at least 48 hours prior to test. Tricyclic antidepressants and labetalol and sotalol (beta blockers) may elevate levels of metanephrines. If clinically feasible, these medications should be discontinued at least 1 week before collection.

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


Specimen Minimum Volume

3 mL

Forms

If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.

 

 

 

Specimen Stability Information

Specimen Type Temperature Time Special Container
Urine Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  14 days

Reject Due To

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

Cautions

While screening for pheochromocytoma is best accomplished by measuring plasma free fractionated metanephrines (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 [MAO] inhibitors, methyldopa, phenacetin, ephedrine, or epinephrine).

 

This method is also not subject to the known interference of acetaminophen, which is seen with the plasma metanephrine high performance liquid chromatography-electrochemical detection method.

 

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 Information

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. 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.

Method Name

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

CRETR: Enzymatic Colorimetric Assay

Report Available

3 to 5 days

Reporting Name

Metanephrines, Fract., Random, U

Reference Values

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

≥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

≥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

≥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

≥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

≥70 years: 230-821 mcg/g creatinine

Interpretation

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.

Method Description

Metanephrine and Normetanephrine:

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; Lam L, Woollard GA, Teague L, Davidson JS. Clinical validation of urine 3-methoxytyramine as a biomarker of neuroblastoma and comparison with other catecholamine-related biomarkers. Ann Clin Biochem. 2017 Mar;54(2):264-272)

 

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)

Day(s) Performed

Monday through Friday

Clinical Reference

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 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: 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 July 20, 2021. 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 Nov;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 Jan;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 Sep-Oct;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 Mar;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 Oct;21(10):1527-1533. doi: 10.1111/jch.13657

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

83835

82570

LOINC Code Information

Test ID Test Order Name Order LOINC Value
METRN Metanephrines, Fract., Random, U 68317-7

 

Result ID Test Result Name Result LOINC Value
21546 Metanephrine/Creatinine 9645-3
CRETR Creatinine, Random, U 2161-8
21547 Normetanephrine/Creatinine 13783-6
21548 Total Metanephrine/Creatinine 13771-1

Profile Information

Test ID Reporting Name Available Separately Always Performed
METAU Metanephrines, Fractionated, U No Yes
CRETR Creatinine, Random, U Yes, (Order RCTUR) Yes
Laboratory Test Directory Additional Information:

Former Epic Code: LAB3157