What is a normal plasma metanephrine level?

Normal Plasma Metanephrine Levels

Normal plasma free metanephrine levels range from 0.06 to 0.63 nmol/L (mean 0.19 nmol/L), and normal plasma free normetanephrine levels range from 0.12 to 0.73 nmol/L (mean 0.38 nmol/L). 1

Reference Range Details

• These reference ranges were established in normal volunteers and inpatients using liquid chromatography with electrochemical detection 1
• The upper limit of normal for plasma free metanephrines has been validated across multiple studies with high diagnostic accuracy (specificity 89-98%) 2, 3

Clinical Context for Interpretation

Elevations above the upper limit of normal should be interpreted based on the degree of elevation:

• Levels ≥4 times the upper limit of normal are highly consistent with pheochromocytoma/paraganglioma and warrant immediate imaging 2, 4, 3
• Levels 2-4 times the upper limit of normal suggest possible pheochromocytoma; repeat testing in 2 months and consider genetic testing 2, 4, 3
• Levels 1-2 times the upper limit of normal may represent false positives; consider repeat testing in 6 months and clonidine suppression testing 2, 4, 3

Important Caveats About False Elevations

Several conditions can cause mild elevations in plasma metanephrines without pheochromocytoma:

• Chronic kidney disease patients, particularly those on dialysis, frequently have elevated plasma free metanephrines (57.7% of hemodialysis patients exceed the upper limit of normal) 5
• Hypertensive patients with obesity or obstructive sleep apnea may have elevated levels 2
• Tricyclic antidepressants can cause false positive elevations 2
• False positive elevations are usually <4 times the upper limit of normal 2

Optimal Collection Technique

To minimize false positives, plasma free metanephrines should ideally be collected from an indwelling venous catheter after the patient has been lying supine for 30 minutes 2, 4, 3. This technique reduces stress-related catecholamine release that can elevate metanephrine levels.

Diagnostic Performance

• Plasma free metanephrines demonstrate 96-100% sensitivity and 89-98% specificity for diagnosing pheochromocytoma 2, 3
• Normal plasma metanephrine concentrations effectively exclude pheochromocytoma (100% negative predictive value) 6
• All patients with confirmed pheochromocytoma had plasma free metanephrine concentrations at least 27% above the upper limit of the reference range 7