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HelpEpic 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
UrineSpecimen Required
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.
Specimen Minimum Volume
3 mL
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.Day(s) Performed
Monday through Friday
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
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. Both are further metabolized to vanillylmandelic acid.
Pheochromocytoma cells are also able to oxymethylate catecholamines into metanephrines that are secreted into circulation.
Cautions
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.
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.
Reporting Name
Metanephrines, Fract., Random, UMethod Name
METAU: Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
CRETR: Enzymatic Colorimetric Assay
Method Description
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)
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 |
Report Available
3 to 5 daysTest Classification
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.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;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
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| METAU | Metanephrines, Fractionated, U | No | Yes |
| CRETR | Creatinine, Random, U | Yes, (Order RCTUR) | Yes |
Forms
If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.
Former Epic Code: LAB3157