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Interpretive Handbook

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Test 83006 :
Metanephrines, Fractionated, 24 Hour, Urine

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."

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

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).

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 <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

> or =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

> or =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

> or =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

> or =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

> or =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

Clinical References 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


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