normetanephrine

Normetanephrine is the O-methylated metabolite of the catecholamine norepinephrine. It is produced mainly by the enzyme catechol-O-methyltransferase (COMT) from norepinephrine and can be found in plasma and urine as part of normal catecholamine turnover. In the body, norepinephrine released from sympathetic nerve endings and the adrenal medulla is metabolized by COMT to normetanephrine, which can then be further processed by monoamine oxidase (MAO) to other metabolites such as 3-mydroxy-4-hydroxyphenylglycol (MHPG) and vanillylmandelic acid (VMA).

Clinically, normetanephrine is used as a biomarker in the biochemical evaluation of pheochromocytoma and paraganglioma. Measurement of plasma free normetanephrine, often together with metanephrine, provides high sensitivity for detecting these catecholamine-secreting tumors. Analytically, these metabolites are typically measured by high-performance liquid chromatography with electrochemical detection or, more commonly today, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reference ranges vary by assay and laboratory, and results should be interpreted in the context of clinical findings and concurrent testing.

Pre-analytical factors can influence results. For plasma testing, resting supine positioning, proper sample handling, and avoidance of certain drugs or acute stress may be important for accuracy. Elevated levels of normetanephrine (in combination with metanephrine) strongly support a diagnosis of pheochromocytoma or paraganglioma, while normal results help exclude these conditions in the appropriate clinical setting.