Detection of spot urinary free metanephrines and 3-methoxytyramine with internal reference correction for the diagnosis of pheochromocytomas and paragangliomas.

Detection of normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT) could be used to diagnose pheochromocytomas and paragangliomas (PPGLs). The accuracy for the diagnosis of PPGLs is only 6% by virtue of the classic symptom triad. In addition, false-positive results were found using plasma free MNs as biomarkers. Spot urinary free metanephrines (MNs) presented high specificity for PPGLs diagnosis in our previous work by HPLC with the electrochemical detection. Whereas, MNs and creatinine (Cr) need to be detected separately. A simple and specific method was urgently needed for the diagnosis of PPGLs. Here, we established a new HPLC method for spot urinary free MNs and 3-MT by the fluorescence detection and Cr by the ultraviolet detection simultaneously. It was worth mentioning that Cr for the virtue of being fairly constant in a given subject was used as an internal reference correction to eliminate the effect of spot urine volume for the diagnosis of PPGLs. Thirty-seven patients with PPGLs and 164 control subjects were detected by the established method and the peak area ratios of MNs and 3-MT to Cr were used innovatively for the diagnosis of PPGLs. The results showed acceptable precisions and recoveries. The sensitivities of the method were 94.6%, 91.9% and 86.5% and the specificities were 96.3%, 93.9% and 82.3%, respectively by the peak area of NMN/Cr, MN/Cr and 3-MT/Cr for the diagnosis. The established method provides a promising way for simple, rapid and accurate diagnosis of PPGLs.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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