From the Guidelines
Metanephrines are catecholamine metabolites that serve as crucial diagnostic markers for pheochromocytoma and paraganglioma, measured in plasma or urine to detect these rare, catecholamine-producing tumors. These substances are produced when catecholamines (such as adrenaline and noradrenaline) are broken down by the enzyme catechol O-methyltransferase, resulting in the formation of normetanephrine and metanephrine 1. The measurement of metanephrines is a sensitive and specific test for diagnosing pheochromocytoma and paraganglioma, with plasma free metanephrines offering a sensitivity of 96%−100% and specificity of 89%−98%, while urinary fractionated metanephrines have a sensitivity of 86%−97% and specificity of 86%−95% 1. Key points to consider when interpreting metanephrine levels include:
- Elevated levels can be caused by various factors, including obesity, obstructive sleep apnea, and certain medications like tricyclic antidepressants 1.
- Levels that are less than 4 times the upper limit of normal may require repeat assessment to confirm the presence of a tumor 1.
- Further evaluation using clonidine-suppression testing can help differentiate between true positives and false positives, with a specificity of 100% and sensitivity of 96% for failure to reduce plasma metanephrines by 40% 1. The importance of accurate diagnosis lies in the potential for these tumors to cause significant morbidity and mortality if left untreated, emphasizing the need for timely and precise biochemical testing, such as metanephrine measurement, in the diagnostic workup of suspected pheochromocytoma or paraganglioma 1.
From the Research
Definition of Metanephrines
- Metanephrines are the O-methylated metabolites of catecholamines, specifically epinephrine and norepinephrine 2
- They are produced by the enzyme catechol-O-methyltransferase (COMT) and include metanephrine and normetanephrine (NMN) 2
Types of Metanephrines
- Normetanephrine: a metabolite of norepinephrine, providing an index of norepinephrine released during sympathetic nervous system activity 2
- Metanephrine: a metabolite of epinephrine, providing an indication of adrenal medullary metabolism of epinephrine prior to its discharge into the circulation 2
Clinical Significance of Metanephrines
- Measurement of metanephrines, especially plasma metanephrine, can be helpful in the diagnosis of pheochromocytoma 3, 4, 2, 5, 6
- Elevated levels of metanephrines can indicate catecholamine excess, which is a characteristic of pheochromocytoma 3, 4, 5, 6
- Plasma metanephrines have been shown to be a sensitive and specific test for the diagnosis of pheochromocytoma, with a sensitivity of 100% and a negative predictive value of 100% 6