Martínez-Morillo Eduardo, Valdés Gallego Nuria, Eguia Ángeles Edwin, Fernández Fernández Juan Carlos, Prieto García Belén, Álvarez Francisco V
Laboratorio de Medicina, Servicio de Bioquímica Clínica, Hospital Universitario Central de Asturias, Oviedo, España.
Servicio de Endocrinología, Hospital Universitario Central de Asturias, Oviedo, España.
Endocrinol Diabetes Nutr (Engl Ed). 2019 May;66(5):312-319. doi: 10.1016/j.endinu.2018.08.009. Epub 2018 Nov 1.
Pheochromocytoma and paraganglioma are uncommon tumors whose best known symptoms include high blood pressure, palpitations, headache, and sweating. Clinical identification is not easy, however, and requires biochemical tests that allow for early diagnosis, including measurement of metanephrines levels. The aim of this study was to assess the diagnostic performance of plasma free metanephrines (PMETs) and to verify the transferability of the reference values used.
PMETs levels were measured by liquid chromatography coupled to tandem mass spectrometry. Other biochemical tests evaluated (plasma catecholamine, urine metanephrine, catecholamine and vanilmandelic acid levels) were performed by liquid chromatography with electrochemical detection. Requests of these tests from 01/09/2015 to 31/10/2017 were reviewed, and both the reference values (document EP28-A3c) and the parameters of biological variation (Fraser method) for PMETs were estimated.
The study sample consisted of 1,279 patients (61.3% females) aged 0-90 years, including 19 with pheochromocytoma/paraganglioma. Tests requested included: PMETs (n=662), catecholamines (n=589), metanephrines (n=586), and vanilmandelic acid (n=513) in urine, and plasma catecholamines (n=228). Tests with higher sensitivity were urinary fractionated metanephrines (91.7%) and PMETs (82.4%). When performance was compared in patients with both tests (n=243), they detected the same number of tumors (90.9%), but PMETs showed greater specificity (93.5% vs 88.8%). Plasma normetanephrine levels showed a significant association with age (rho=0.19, P<.0001).
PMETs and urinary fractionated metanephrines are the biochemical tests with better performance in diagnosis of pheochromocytomas/paragangliomas.
嗜铬细胞瘤和副神经节瘤是罕见肿瘤,其最常见症状包括高血压、心悸、头痛和出汗。然而,临床诊断并不容易,需要进行生化检测以实现早期诊断,包括测定甲氧基肾上腺素水平。本研究旨在评估血浆游离甲氧基肾上腺素(PMETs)的诊断性能,并验证所使用参考值的可转移性。
采用液相色谱-串联质谱法测定PMETs水平。其他评估的生化检测(血浆儿茶酚胺、尿甲氧基肾上腺素、儿茶酚胺和香草扁桃酸水平)采用液相色谱-电化学检测法进行。回顾了2015年9月1日至2017年10月31日期间这些检测的申请情况,并估计了PMETs的参考值(文件EP28-A3c)和生物学变异参数(弗雷泽方法)。
研究样本包括1279例年龄在0至90岁之间的患者(61.3%为女性),其中19例患有嗜铬细胞瘤/副神经节瘤。申请的检测项目包括:尿中的PMETs(n = 662)、儿茶酚胺(n = 589)、甲氧基肾上腺素(n = 586)和香草扁桃酸(n = 513)以及血浆儿茶酚胺(n = 228)。敏感性较高的检测项目是尿中分离的甲氧基肾上腺素(91.7%)和PMETs(82.4%)。当对两项检测均进行检测时(n = 243),它们检测出的肿瘤数量相同(90.9%),但PMETs显示出更高的特异性(93.5%对88.8%)。血浆去甲氧基肾上腺素水平与年龄呈显著相关性(rho = 0.19,P <.0001)。
PMETs和尿中分离的甲氧基肾上腺素是诊断嗜铬细胞瘤/副神经节瘤性能更佳的生化检测项目。