metanephrines

Metanephrines are metabolites of catecholamines produced during the breakdown of adrenaline (epinephrine) and noradrenaline (norepinephrine). The principal circulating metanephrine is formed from epinephrine, while normetanephrine is formed from norepinephrine. Most metanephrine and normetanephrine are generated by catechol-O-methyltransferase (COMT) activity in sympathetic nerves and the adrenal medulla. They can be measured in plasma or urine and reflect catecholamine turnover more reliably than measurements of parent catecholamines alone.

Clinical use of metanephrines centers on the evaluation of pheochromocytoma and paraganglioma. Plasma free metanephrines or urinary metanephrines are commonly measured in suspected cases. Plasma free metanephrines tend to have high sensitivity, whereas urinary fractionated metanephrines are useful when plasma testing is not available or results are equivocal. Positive results are typically followed by imaging studies to localize a tumor. Preanalytic factors can influence levels; stress, acute illness, medications (certain antidepressants, decongestants), smoking, caffeine intake, and improper sample handling can cause false positives, so proper resting/supine positioning and appropriate collection are recommended.

Interpretation of results depends on clinical context. Levels above reference ranges in plasma or urine support a diagnosis of catecholamine-secreting tumors, but false positives must be considered. Normal results do not completely exclude pheochromocytoma in all cases, and repeat testing or alternative assays may be needed. Metanephrines may be reported as total or individual metabolites (metanephrine and normetanephrine); clinical correlation with symptoms and imaging remains essential.