| Background:Pheochromocytomas and paragangliomas(PPGLs) are endocrine neoplasms of chromaffin cells that arise from adrenal medulla or extra-adrenal paraganglia. PPGLs typically secrete excessive catecholamines, which lead to increased blood pressure, headache, palpitation and hyperhidrosis symptoms. The fatal complications include hypertensive crisis, heart failure and stroke et al. Recently, the measurements of plasma free metanephrines(MNs) and 24-h urinary fractionated MNs have been proposed for the biochemical screening of PPGLs. However, specificity of plasma free MNs is inadequate and the false positive result remains a problem. The collection of 24-h urine sample is inconvenient, poor patient compliance and limiting use in outpatient service. Therefore, the more specific and convenient diagnosis of PPGLs remains importance.Objective:To investigate diagnostic and prognostic performances of spot urinary free MNs for PPGLs and provide the more specific and convenience diagnosis and prognosis for PPGLs.Methods:1. The spot urinary and plasma free normetanephrine(NMN) and metanephrine(MN) concentrations were measured by the high performance liquid chromatography and electrochemical detection(HPLC-ED) method. All spot urine and plasma samples were collected simultaneously. The creatinine(Cr) concentration was used to correct urine volume.2. Determining the concentrations of spot urinary and plasma free metanephrines(MNs) in healthy volunteers(n=44), essential hypertension patients(n=50), other adrenal tumor mass patients(n=61), patients with pheochromocytoma(n=28), and investigating the diagnostic performances of spot urinary free MNs for PPGLs compared with that of plasma free MNs.3. The Pre- and post-operative measurements of spot urinary and plasma free MNs were performed on the fourteen PPGLs patients, and investigating the prognostic efficiency of spot urinary free MNs for PPGLs compared with that of plasma free MNs.4. Investigating the correlation between tumor size and free MNs, and discussing correlation between spot urinary and plasma free MNs.Results:1. In both spot urine and plasma, the concentration of free MNs in patients with PPGLs was significantly higher than that of the three control groups(P < 0.001), but the measure of plasma free MNs yielded more false positive results. The sensitivities of spot urinary and plasma free MNs were similar. The specificities of spot urinary free NMN/Cr and MN/Cr were 98.7% and 93.6%, respectively, which were significantly higher than that of plasma free NMN and MN at 93.0% and 84.5%, respectively. Meanwhile, the positive likelihood ratios for spot urinary free NMN/Cr and MN/Cr were 69.21 and 13.29, respectively. The positive likelihood ratios for free plasma NMN and MN were only 12.68 and 5.30, respectively.2. After resection of PPGLs, the MNs level in spot urine and plasma presented a large decrease, which showed the significant differences compared with the preoperative MNs level(P < 0.01). Spot urinary free MNs concentration decreased(P < 0.001) more amount than that of plasma, and all patients turned back to normal. Besides, free MNs concentration of spot urine sample collected at one day after surgery also decline to normal. However, the postoperative plasma of two patients presented a high concentration of free MNs and yielded false positive results.3. The correlation between spot urinary free MNs/Cr and tumor size: NMN/Cr, r = 0.51, P < 0.05; MN/Cr, r = 0.52, P < 0.05.The correlation between plasma free MNs and tumor size: NMN, r = 0.47, P = 0.06; MN, r = 0.55, P < 0.05.The correlation between spot urinary and plasma free MNs: NMN, r = 0.71, P < 0.001; NMN/Cr, r = 0.80, P < 0.001; MN, r = 0.68, P < 0.001; MN/Cr, r = 0.72, P < 0.001.Conclusions:Compared with plasma free MNs, spot urinary free MNs/Cr showed a superior specificity for diagnosis of PPGLs, and performed excellently to evaluate the prognosis of PPGLs. Besides, spot urinary free MNs/Cr presented a better correlation with tumor size compared with plasma free MNs, and spot urinary free MNs/Cr correlated significantly with plasma free MNs concentration. Based on the convenience and non-invasion, spot urinary free MNs provided a better maker for diagnosis and prognosis of PPGLs. |
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