Plasma fractionated total metanephrines for biochemical diagnosis of neuroblastoma.

Abstract

9571 Background: Urine catecholamines and their metabolites are used for diagnosis and follow-up of patients with neuroblastoma. O-methylated metabolites of catecholamines (plasma free or total metanephrines) are the most sensitive tests for diagnosis of pheochromocytoma. We postulate that neuroblastoma transforms catecholamines into metanephrines which may be more sensitive and specific than urine catecholamines for diagnosis and follow-up of the disease. The aim of the study was to establish reference values for plasma fractionated metanephrines in children and provide preliminary results on their diagnostic values. Methods: We included into the study 191 healthy children aged 0-17 years needing a venous puncture. 2 ml of heparinized blood were drawn to measure plasma total metanephrines. Additionally, we included ten patients with neuroblastoma to evaluate the diagnostic utility of the test. Results: Upper reference limit of total plasma normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) were: 9.67 nmol/l (95% CI: 8.32-10.1) for NMN, 4.95 nmol/l (95% IC: 4.19-6.05) for MN, 5.8 nmol/l (95% IC: 4.85-7.37) for MT. There was no significant difference between boys and girls. A linear trend gradually decreasing from birth to 17 years was observed for NMN and MT which was statistically significant for both. Plasma concentration of MN showed a non-linear relationship to age. In patients with neuroblastoma, plasma total MT and NMN measurements were highly sensitive and specific at diagnosis. The highest sensitivity and specificity (100% and 99.48%, respectively) were achieved for plasma total NMN with a cutoff at 19.64 nmol/l (odds ratio 1.18, CI 1.06-1.31) and for plasma total MT (sensitivity 100% and specificity 98.95%) with a cutoff at 9.43 nmol/l (odds ratio 1.8, CI 1.32-2.46). Conclusions: These preliminary results provide pediatric reference limits for total plasma metanephrines and suggest a promising role in diagnosis and follow-up of neuroblastoma patients. Further data are necessary to confirm its validity. No significant financial relationships to disclose.