Modern biochemical methods for the diagnostics of pheochromocytoma

Abstract

The objective of the present work was to estimate the possibility of using the ELISA technique for the quantitative analysis of the metanephrine and normetanephrine levels in urine and to determine the cross-off points for the discrimination between their normal and pathological values for the purpose of diagnostics of pheochromocytoma. Methylated derivatives of adrenaline and noradrenaline were measured in 3,234 urine sample obtained from the patients presenting with elevated arterial pressure, resistance to therapy, and adrenal mass lesions who had visited the inpatient and outpatient departments of the Endocrinological Research Centre during the past 4 years. The measurement of total metanephrine and normetanephrine (free plus deconjugated fractions) was performed using commercial ELISA kits (IBL, Hambutg, Germany). The content of normetanephrine over 612 mcg in daily urine samples was shown to be the borderline between the normal values and those suggesting diagnosis of pheochromocytoma. The sensitivity of this assay was 97,5% (95% CI 91,1-99,6%), specificity 100% (95% CI 93,8-100%). For metanephrine, the level of more than 550 mcg/24 hours was the borderline between the normal values and those suggesting diagnosis of pheochromocytoma. The sensitivity of the method was 100% (95% CI 88-100%), specificity - 96% (95% CI 86-99,4%). The biochemical diagnosis of pheochromocytoma was confirmed by the reference pathomorphological method in 99% of the cases. The incidence of pheochromocytoma predicted by the biochemical analysis of the urine samples delivered to the laboratory during 4 years from the patients with the tentative diagnosis of this pathology (based on the elevated arterial pressure and the presence of adrenal mass lesions) was 4% on the average. It is concluded that the application of ELISA in a "manual" mode provides high sensitivity and specificity of quantitative determination of metanephrines in daily urine comparable to those achieved with the widely used but more expensive high performance liquid chromatography.