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Test ID METAF Metanephrines, Fractionated, 24 Hour, Urine

Reporting Name

Metanephrines, Fractionated, 24h, U

Useful For

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

 

Confirming positive plasma metanephrine results

Specimen Type

Urine


Advisory Information


 



Necessary Information


24-Hour volume is required.



Specimen Required


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, you may consider consultation with a specialist in endocrinology or hypertension.

Supplies: Urine Tubes, 10 mL (T068)

Container/Tube: Plastic urine tube (T068)

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 in Special Instructions for multiple collections.


Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time
Urine Refrigerated (preferred) 7 days
  Frozen  14 days
  Ambient  7 days

Reference Values

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

≥18 years: 44-261 mcg/24 hours

Reference values have not been established for patients that are <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

≥18 years: 30-180 mcg/24 hours

Reference values have not been established for patients that are <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

≥70 years: 148-560 mcg/24 hours

Reference values have not been established for patients that are <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

≥70 years: 148-560 mcg/24 hours

Reference values have not been established for patients that are <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

≥70 years: 246-753 mcg/24 hours

Reference values have not been established for patients that are <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

≥70 years: 180-646 mcg/24 hours

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

Hypertensives: <1,300 mcg/24 hours

Day(s) and Time(s) Performed

Monday through Friday; 4 p.m.

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 U.S. Food and Drug Administration.

CPT Code Information

83835

LOINC Code Information

Test ID Test Order Name Order LOINC Value
METAF Metanephrines, Fractionated, 24h, U In Process

 

Result ID Test Result Name Result LOINC Value
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

Clinical Information

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."

Interpretation

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

 

Total urine metanephrines 1,300 mcg/24 hours and lower can be detected in nonpheochromocytoma hypertensive patients.

 

Further clinical investigation (eg, radiographic studies) is warranted in patients whose total urinary metanephrine levels are above 1,300 mcg/24 hours (approximately 2 times the upper limit of normal). For patients with total urinary metanephrine levels below 1,300 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.

Clinical Reference

1. Hernandez FC, Sanchez M, Alvarez A, et al: A five-year report on experience in the detection of pheochromocytoma. Clin Biochem 2000;33:649-655

2. Pacak K, Linehan WM, Eisenhofer G, et al: Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 2001;134:315-329

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

Analytic Time

4 days (not reported on Sundays)

Method Name

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

Urine Preservative Collection Options

Ambient

No

Refrigerated

Yes

Frozen

Yes

6N HCl

Yes

50% Acetic Acid

Preferred

Na(2)CO(3)

Yes

Toluene

Yes

6N HNO(3)

Yes

Boric Acid

Preferred

Thymol

No

Forms

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

(http://www.mayomedicallaboratories.com/it-mmfiles/oncology-request-form.pdf)