Symptom-dependent cut-offs of urine metanephrines improve diagnostic accuracy for detecting pheochromocytomas in two separate cohorts, compared to symptom-independent cut-offs

The development of advanced imaging techniques has increased the detection of subclinical pheochromocytomas. Because of the substantial proportions of subclinical pheochromocytomas, measurement of urine metanephrine concentrations is crucial due to detect or exclude pheochromocytoma. Although urine metanephrines are elevated in symptomatic subjects, diagnostic cut-offs according to the presence of adrenergic symptoms have not been studied. Pheochromocytomas patients who underwent adrenalectomy at Samsung Medical Center and a control group were compared to determine cut-off concentrations of urine metanephrines. An independent population was analyzed for urine metanephrines with different kits to validate the improvement in diagnostic accuracy using adjusted cut-offs. Symptom-dependent cut-offs of urine metanephrines were higher for symptomatic patients (307 mu g/day in males, 235 mu g/day in females for urine metanephrine, and 1,045 mu g/day in males and 457 mu g/day in females for urine normetanephrine) than for asymptomatic patients (206 mu g/day in males, 199 mu g/day in females for urine metanephrine, and 489 mu g/day in males and 442 mu g/day in females for urine normetanephrine). Symptom-dependent cut-offs of urine metanephrines improved a specificity from 92.7 % to 96.3 % and a high sensitivity of 97.8 % was maintained. Using the Symptom-dependent cut-offs raised diagnostic accuracy by 5.5 % (p < 0.001). Similar trend was also observed in an independent population using different hormone kits. Using symptom-dependent cut-offs of urine metanephrines in symptomatic patients for pheochromocytomas resulted in a significant improvement in diagnostic accuracy in two separate cohorts.