Background: Measurements of plasma free or urinary fractionated metanephrines are both recommended for diagnosis of pheochromocytoma and paraganglioma (PPGL). What test offers optimal diagnostic accuracy, whether urinary free metabolites offer advantages over deconjugated metabolites and the relative utilities of measurements of methoxytyramine remain unclear.
Methods: LC-MS/MS measurements of urinary deconjugated and plasma and urinary free metanephrines and methoxytyramine were prospectively carried out in 2093 patients with suspected PPGLs, which were confirmed in 210 patients.
Results: Areas under receiver-operating characteristic (ROC) curves for diagnosis of PPGLs using normetanephrine and metanephrine did not differ between plasma and urinary free metabolites (0.984 vs 0.975), but were higher (P=0.0051) for plasma than urinary deconjugated metabolites (0.970). Areas under ROC curves were higher (P<0.0001) for plasma free methoxytyramine (0.883) than urinary free (0.713) and deconjugated (0.705) methoxytyramine. Thus, with addition of methoxytyramine, areas under ROC curves were higher (P<0.02) for plasma free (0.991) than both urinary free (0.975) and deconjugated (0.970) metabolites. Using optimized cut-offs, measurements of plasma free metabolites offered higher diagnostic sensitivity (98.6%vs94.9%vs94.7%; P<0.04) and specificity (95.2%vs92.4%vs88.5%; P<0.0001) than urinary free and deconjugated metabolites. Sensitivity between urine tests did not differ but specificity was higher (P<0.001) for tests of urinary free than deconjugated metabolites.
Conclusions: Diagnosis of PPGLs using urinary free metanephrines rather than routinely used deconjugated metabolites provides advantages of fewer false-positive results. With inclusion of methoxytyramine, which shows limited diagnostic utility for measurements in urine, the plasma test shows superior diagnostic performance than tests of both urinary free and deconjugated metabolites