The role of urinary fractionated metanephrines in the diagnosis of phaeochromocytoma

Abstract

Background & objectives: Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma.

Methods: Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit.

Results: Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 μg/day had a low sensitivity and uNMN >600 μg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent.

Interpretation & conclusions: ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population.

Fig. 1

Cut-off values for 24 h urinary metanephrine (μMN) and normetanephrine (μNMN) in μg/day. The dotted lines represent the cut-off values defined by the upper limit of normal as stated by the assay manufacturer and the broken lines twice the upper limit. In the phaeochromocytoma group, circles (O) and triangles (Δ), adrenal and extra-adrenal tumour, respectively. (□), urinary normetanephrine levels in controls. (■), urinary metanephrine levels in controls.

Fig. 2

ROC curve for the 24 h urinary metanephrine (uMN), normetanephrine (μNMN) and a combination of both (μMN+μNMN).