Patient Preparation: Drugs and medications may affect results and should be discontinued for at least 72 hours prior to specimen collection, if possible. Collection of the specimen after the patient has rested for 15 minutes in a supine position is recommended.

Preferred Minimum: 1 mL plasma from lavender top (EDTA) tube
Absolute Minimum: 0.3 mL plasma from lavender top (EDTA) tube

2-5 days upon receipt in reference laboratory

METANEPHRINE, FREE

<0.50 nmol/L

NORMETANEPHRINE, FREE

<0.90 nmol/L

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.(1,2)

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.(3) The recommended second-line test is measurement of fractionated 24-hour urinary metanephrines (METAF / Metanephrines, Fractionated, 24 Hour, Urine). 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.

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:

• Monoamine oxidase inhibitors (MAOI-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, particularly 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, mescal, or peyote

The observed elevations of plasma metanephrines are usually minor.

We are currently not aware of any substances that interfere directly with 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.

Quantitative Liquid Chromatography-Tandem Mass Spectrometry