Metanephrines, Fractionated, Free, Plasma (PMET)

Test Code: METFRSO

Overview
Ordering
Specimen
Performing
Clinical/Interpretive
Contacts
Coding

Synonyms/Keywords

Fractionated metanephrines +, Free Metanephrine, Metanephrines free, plasma, NMN (Normetanephrines), plasma, Normetanephrine, (NMN), free, Normetanephrines, plasma

Useful For

Screening test for presumptive diagnosis of catecholamine-secreting pheochromocytomas or paraganglioma

Specimen Requirements

Specimen Type	Preferred Container/Tube	Acceptable Container/Tube	Specimen Volume	Specimen Minimum Volume (allows for 1 repeat)	Pediatric Minimum Volume (no repeat)
Plasma	EDTA Lavender Top Tube (LTT)		1 mL	0.3 mL

Collection Processing Instructions

Patient Preparation: Use of an Epi-pen within the last 7 days may produce inaccurate results.

Spin down within 2 hours of draw.

Plasma must be separated from red blood cells within 2 hours of collection.

Submit sample in a plastic vial.

Specimen Stability Information

Specimen Type	Temperature	Time
EDTA Plasma	Frozen (preferred)	14 days
EDTA Plasma	Refrigerated	7 days

Rejection Criteria

Gross Hemolysis

Interference

Use of an Epi-pen within the last 7 days may produce inaccurate results.

While most circulating metanephrines are derived directly from adrenal secretion, peripheral conversion of catecholamines makes a small contribution. Therefore, substances that increase endogenous catecholamine levels can result in borderline elevations of plasma metanephrines. These include:

-Monamine oxidase inhibitors (MOIs-a class of antidepressants with marked effects on catecholamine levels, particularly if the patient consumes tyrosine-rich foods such as nuts, bananas, or cheese)

-Catecholamine reuptake inhibitors including cocaine and synthetic cocaine derivatives such as many local anesthetics, some of which also are antiarrhythmic drugs (eg, lidocaine)

-Some anesthetic gases, particularly halothane

-Withdrawal from sedative drugs, medical or recreational, in particular alcohol, benzodiazepines (eg, Valium), opioids, and some central acting antihypertensive drugs, particularly clonidine, but, generally not cannabis or other hallucinogens such as lysergic acid diethylamide (LSD), mescal, or peyote

The observed elevations of plasma metanephrines are usually minor.

We are currently not aware of any substances that interfere directly in the assay.

Artifactually decreased plasma metanephrine levels may be observed when patients are already receiving metyrosine treatment. This drug may be administered in suspected or confirmed cases of pheochromocytoma while awaiting definitive treatment. It inhibits tyrosine hydroxylase, the enzyme that catalyzes the first step in catecholamine synthesis.

Performing Laboratory Information

Performing Location	Day(s) Test Performed	Report Available	Methodology/Instrumentation
Mayo Clinic Laboratories	Monday through Saturday	2 to 4 days	Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Reference Lab

Mayo Clinic Laboratories

Test 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 (collectively referred to as metanephrines) are the 3-methoxy metabolites of epinephrine and norepinephrine, respectively. The metanephrines are stable metabolites and are cosecreted directly with catecholamines by pheochromocytomas and other neural crest tumors. This results in sustained elevations in plasma free metanephrine levels, making them more sensitive and specific than plasma catecholamines in the identification of pheochromocytoma patients. Metanephrine and normetanephrine are both further metabolized to conjugated metanephrines and vanillylmandelic acid.

Reference Range Information

Metanephrine, Free: < 0.50 nmol/L
Normetanephrine, Free: < 0.90 nmol/L

Interpretation

In the normal population, plasma metanephrine and normetanephrine levels are low, but in patients with pheochromocytoma or paragangliomas, the concentrations may be significantly elevated. This is due to the relatively long half-life of these compounds, ongoing secretion by the tumors and, to a lesser degree, peripheral conversion of tumor-secreted catecholamines into metanephrines.

Measurement of plasma free metanephrines appears to be the best test for excluding pheochromocytoma. The test's sensitivity approaches 100%, making it extremely unlikely that individuals with normal plasma metanephrine and normetanephrine levels suffer from pheochromocytoma or paraganglioma.

Due to the low prevalence of pheochromocytomas and related tumors (<1:100,000), it is recommended to confirm elevated plasma free metanephrines with a second, different testing strategy in order to avoid large numbers of false-positive test results. The recommended second-line test is measurement of fractionated 24-hour urinary metanephrines. In most cases this strategy will suffice in confirming or excluding the diagnosis. Occasionally, it will be necessary to extend this approach if there is a very high clinical index of suspicion or if test results are nonconclusive. In these cases, repeat plasma and urinary metanephrines testing, additional measurement of plasma or urinary catecholamines, or imaging procedures might be indicated.

Elevated results are reported with appropriate comments.

Outreach CPTs

CPT	Modifier (if needed)	Quantity	Description	Comments
83835