Test ID: METAF
Metanephrines, Fractionated, 24 Hour, Urine
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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 and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular 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
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
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
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Plastic, 10-mL urine tube (Supply 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:
1. 24-Hour volume is required.
2. See Urine Preservatives in Special Instructions for multiple collections.
3. Tricyclic antidepressants, labetalol, and sotalol medications may elevate levels of metanephrines producing results which 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.
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 | Yes |
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Urine | Refrigerated (preferred) | 7 days |
| Frozen | 14 days | |
| Ambient | 7 days |
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 <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 <24 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 <24 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 <24 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 <24 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 <24 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 <24 months of age.
Hypertensives: <1,300 mcg/24 hours
Interpretation Provides information to assist in interpretation of the test results
Increased metanephrine/normetanephrine levels are found in patients with pheochromocytoma and tumors derived from neural crest cells.
Total urine metanephrines < or =1,300 mcg/24 hours can be detected in non-pheochromocytoma hypertensive patients.
Further clinical investigation (eg, radiographic studies) are warranted in patients whose total urinary metanephrine levels are >1,300 mcg/24 hours (approximately 2 times the upper limit of normal). For patients with total urinary metanephrine levels of <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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Tricyclic antidepressants, levodopa, and significant physical stress (eg, hypertensive stroke) may elevate levels of metanephrines. If clinically feasible, these medications should be discontinued at least 1 week before collection.
This test utilizes a high-performance 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, MAO inhibitors, methyldopa, phenacetin, ephedrine, or epinephrine).
This method is also not subject to the known interference of acetaminophen (seen with the plasma metanephrine HPLC-EC method).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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
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 (d[3]-metanephrine, 200 ng) and deuterated normetanephrine (d[3]-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); d[3]-metanephrine, (183/151); d[3]-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 chromoatography-tandem mass spectometry method for analysis of urinary conjuncted metanephrine and normetanephrine for screening of pheochromocytoma. Clin Chem 2002;48:533-539; Roden M, Raffesberg W, Raber W, et al: Quantification of unconjugated metanephrine in human plasma without interference by acetaminophen. Clin Chem 2001;47:1061-1067)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Saturday; 12 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83835
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 8552 | Metanephrine, U | 19049-6 |
| 21545 | Normetanephrine, U | 2671-6 |
| 83006 | Total Metanephrines, U | 2609-6 |
| TM50 | Collection Duration | 13362-9 |
| VL48 | Urine Volume | 19153-6 |
| 2434 | Comment | 48767-8 |
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