Interpretive Handbook
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Test 83005:
Metanephrines, Fractionated, Random, 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").
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.
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-positives. Twenty-four 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 second-order screening test for the presumptive diagnosis of pheochromocytoma in patients with nonepisodic hypertension
Confirming positive plasma metanephrine results in patients with nonepisodic hypertension
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.
Increased urine metanephrines can be detected in nonpheochromocytoma hypertensive patients; quantification may help distinguish these patients from those with tumor-induced symptoms.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
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/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
> or =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
> or =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
> or =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
> or =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
> or =70 years: 230-821 mcg/g creatinine
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Ito Y, Obara T, Okamoto T, et al: Efficacy of single-voided urine metanephrine and normetanephrine assay for diagnosing pheochromocytoma. World J Surg 1998;22:684-688
2. 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
3. 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
4. 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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