Radioimmunoassay of free plasma metanephrines for the diagnosis of catecholamine-producing tumors

Radioimmunoassay of free plasma metanephrines for the diagnosis of catecholamine-producing tumors
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DOI:
10.1515/cclm-2013-0406
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发表时间:
2014-03-01
影响因子:
6.8
通讯作者:
Said, Toihiri
Said, Toihiri
中科院分区:
医学2区
文献类型:
--
作者:
Pussard, Eric;Chaouch, Amel;Said, Toihiri

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背景:血浆变肾上腺素(MN)的测定为诊断产生儿茶酚胺的肿瘤提供了一种高度敏感的检测方法。色谱测定与电化学或质谱检测是首选的方法,但免疫学测定已经开发出来。方法:采用放射免疫分析法测定533例疑有儿茶酚胺性肿瘤患者的血浆和尿液中MNs、去甲肾上腺素(NE)、肾上腺素(E)、去甲肾上腺素(NMN)、去甲肾上腺素(MN)和儿茶酚胺。采用高效液相色谱安培检测法测定尿和血浆儿茶酚胺和尿MN。结果:59例患者有肿瘤(13例副神经节瘤和46例嗜铬细胞瘤),474例患者的诊断被排除。受试者操作特征曲线确定了血浆NMN的最佳阈值为100 pg/mL(灵敏度96.6%,特异性95.8%),血浆MN的最佳阈值为70 pg/mL(灵敏度61.0%,特异性96.8%)。这些临界值低于生产商建议的值(分别为170和100 pg/mL)。血浆和尿中MNs联合检测的敏感性相似(100%和98%),但高于尿中儿茶酚胺的敏感性(85%,p < 0.001)。血浆MNs联合检测的特异性(95%)高于尿MNs(85%,p < 0.001)和血浆儿茶酚胺(75%,p < 0.001)。使用这些确定的截止值,通过放射免疫测定法测量血浆游离MN代表色谱法的有效替代方法。
Background: The determination of plasma metanephrines (MNs) provides a highly sensitive test for the diagnosis of catecholamine producing tumors. Chromatographic determinations with electrochemical or mass spectrometric detections are the methods of choice, but immunological assays have been developed. This study evaluated the clinical performances of a radioimmunoassay for free MNs in plasma.Methods: MNs, normetanephrine (NMN) and metanephrine (MN) and catecholamines, norepinephrine (NE) and epinephrine (E) were determined in plasma and urine of 533 patients suspected of catecholamine producing tumor. Urinary and plasma catecholamines and urinary MNs were determined by HPLC using amperometric detection. Plasma MNs were purified by solid phase chromatography and quantified by a specific radioimmunoassay.Results: Fifty-nine patients had tumors (13 paraganglioma and 46 pheochromocytoma) and the diagnosis was excluded in 474 patients. Receiver operator characteristic curves have identified optimal thresholds at 100 pg/mL for plasma NMN (sensitivity 96.6% and specificity 95.8%) and 70 pg/mL for plasma MN (sensitivity 61.0% and specificity 96.8%). These cut-off values were lower than those suggested by the manufacturer (170 and 100 pg/mL, respectively). The sensitivity of combined MNs was similar in plasma (100%) and urine (98%) but higher than that of urinary catecholamines (85%, p < 0.001). The specificity of combined MNs in plasma (95%) was higher than urinary MNs (85%, p < 0.001) and plasma catecholamines (75%, p < 0.001).Conclusions: Plasma-free and urinary-total MNs have a better discriminative power than catecholamines in the diagnosis of catecholamines producing tumors. Using these established cut-offs, measurement of plasma-free MN by radioimmunoassay represents an effective alternative to chromatographic methods.