Performance of plasma fractionated free metanephrines by enzyme immunoassay in the diagnosis of pheochromocytoma and paraganglioma in children.

OBJECTIVE: To establish pediatric reference ranges for plasma fractionated free metanephrines by enzyme immunoassay (EIA) and to evaluate its performance in the diagnosis of catecholamine-secreting tumors in the pediatric population.

METHODS: Normotensive children and children with suspected catecholamine-secreting tumors underwent measurement of plasma fractionated metanephrines by EIA to establish pediatric reference ranges. Children with suspected pheochromocytoma or paraganglioma also underwent magnetic resonance imaging or computed tomography from the neck to the pelvis and were followed up for a minimum of 1 year. Diagnosis of pheochromocytoma/paraganglioma was confirmed by histologic examination. Pheochromocytoma/paraganglioma was excluded in children who had a histologic diagnosis other than pheochromocytoma/paraganglioma and in those who had no imaging evidence of tumor and no progression on follow-up.

RESULTS: Plasma fractionated metanephrines were measured in 78 normotensive children (age range, 1.5-17 years) and in 38 children with suspected catecholamine-secreting tumors. Of the 38 children (age range, 6-17 years) with suspected pheochromocytoma/paraganglioma, 17 had a histopathologically proven catecholamine-secreting tumor. The newly derived pediatric upper reference limit for metanephrine (128 pg/mL) was higher than in adults (90 pg/mL), whereas the pediatric upper reference limit for normetanephrine (149 pg/mL) was lower than in adults (180 pg/mL). The manufacturer's reference range for plasma fractionated metanephrines yielded a sensitivity of 100% and a specificity of 85.7%. Use of newly established pediatric reference ranges increased the specificity to 95.2% without altering the sensitivity (100%).

CONCLUSIONS: Plasma fractionated metanephrines by EIA provide an accurate test with good sensitivity and specificity for the diagnosis of pheochromocytoma and paraganglioma in children. Use of pediatric reference ranges improves accuracy of the test.