Value of Plasma Free Metanephrine and Normetanephrine in the Diagnosis of Pheochromocytoma and Paraganglioma
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0113
- VernacularTitle:血浆游离甲氧基肾上腺类物质对嗜铬细胞瘤和副神经节瘤的诊断价值
- Author:
Yao YAO
1
;
Qi-ling FENG
1
;
Yong-jie LI
1
;
Xiao-yun ZHANG
1
;
Ju-ying TANG
1
;
Ying GUO
1
;
Shao-ling ZHANG
1
;
Li YAN
1
Author Information
1. Department of Endocrinology and Metabolism， Sun Yat-sen Memorial Hospital of Sun Yat-sen University， Guangzhou 510120， China
- Publication Type:Journal Article
- Keywords:
pheochromocytoma;
paraganglioma;
metanephrine;
normetanephrine;
diagnosis
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(1):107-116
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the value of plasma free metanephrines， including metanephrine（MN） and normetanephrine（NMN）， collectively referred to as MNs in the diagnosis of pheochromocytoma and paraganglioma （PPGL）. MethodsThe study included 1 631 patients suspected of PPGL from December 2014 to December 2020 in SunYat-sen Memorial Hospital. In these subjects， Plasma free MNs were measured by liquid chromatography-tandem mass spectrometry（LC-MS/MS） before surgery. Receiver operating characteristic （ROC） curves were used to determine the sensitivity and specificity of plasma NMN and MN in the diagnosis of PPGL. ResultsOf the screened patients， 108 patients had pathologically confirmed PPGL and 1 523 patients had definitive diagnoses other than PPGL as a control group. The median value of plasma MN ［0.54（0.17~4.48） nmol/L vs. 0.15（0.11~0.21） nmol/L， P<0.001］ and NMN ［7.48（2.12~15.01） nmol/L vs. 0.32（0.22~0.46） nmol/L， P<0.001］ were significant higher in the PPGL group than in the control group. Using an upper cut-off of 0.395 nmol/L for MN， the sensitivity was 60.2% and the specificity was 97.8%； when using a cut-off of 1.105 nmol/L for NMN， the diagnostic sensitivity was 87.0%， and the specificity was 98.7%. The area under the ROC curve and 95% confidence interval of plasma MN and NMN combined were 0.800（0.743， 0.858）， 0.959（0.932， 0.98） and 0.970（0.944， 0.996）， respectively. Analyzing the false-positive results， it was found that in the control group， 3% of the false-positive cases appeared. The estimated glomerular filtration rate（eGFR） were significantly lower in the false-positive group than in the true-negative group ［74.42（51.04~96.96） mL/min vs. 88.51（72.80~101.83） mL/min， P=0.001］. In 212 patients with eGFR lower than 60 mL/min， the false positive rate was increased to 8%. If the upper limit of the reference interval was increased by 25%， the specificity was increased to 96.7%； when the upper limit of the reference interval was increased by 50%， the specificity was 98.6 %. ConclusionsPlasma free MNs has a great reliability in the diagnosis of PPGL. The negative predictive value is extremely high and close to 100%. Combination analysis of plasma MN and NMN can further improve diagnostic performance. However， a few false positive cases may appear and might be influenced by impaired renal function. In patients with eGFR lower than 60 mL/min， the false positive rate is significantly increasing， which need a 25%-50% increase in the expected upper limit of a reference range to guarantee high specificity.
