摘要
和肽素作为精氨酸加压素(arginine vasopressin,AVP)的稳定替代标志物,在多尿多饮综合征的鉴别诊断中具有重要作用。当前指南建议在高渗盐水、精氨酸输注等功能刺激试验过程中动态检测和肽素水平以协助区分AVP缺乏症(AVP-D)与原发性烦渴。这些方法在诊断价值上已获得验证,但存在一定局限性。因此,寻找更安全、可操作性强且刺激效果明确的替代刺激物成为临床研究关注的方向。此外,现有的和肽素检测只有时间分辨免疫荧光法,可能受到自身抗体、溶血等干扰。本研究旨在使用实验室自建的可靠的液相色谱-串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS)评估生长激素功能试验常用刺激物,包括左旋多巴、胰岛素、胰高血糖素和奥曲肽,对和肽素水平的影响。各有28、7、20和7名进行生长激素功能试验的受试者分别接受了左旋多巴、胰岛素、胰高血糖素和奥曲肽的刺激试验。在基线、30、60、90和120 min(胰高血糖素激发试验是120和180 min)时采血进行生长激素测定,使用LC-MS/MS测定各个时间点的和肽素水平。通过Wilcoxon配对符号秩检验、曼-惠特尼秩和检验和斯皮尔曼分析考察了刺激效果和相关性。研究发现,左旋多巴使和肽素水平最大增加至基线的8.47倍(p<0.0001),胰岛素使其水平最大增加至基线的5.85倍(p=0.0312),胰高血糖素使其水平最大增加至基线的1.43倍(p<0.0001),奥曲肽使其水平最大降低至基线的43%(p<0.05)。和肽素水平变化与生长激素水平变化无显著相关性。在左旋多巴刺激下,AVP-D患者的和肽素最大值显著低于非AVP缺乏症患者(p=0.0002),受试者工作特征曲线下面积为0.98(95%置信区间0.94~1.00,p=0.0021)。本研究显示,左旋多巴和胰岛素能有效刺激和肽素分泌,而奥曲肽则抑制其分泌。LC-MS/MS检测和肽素的方法在诊断AVP-D患者中具有潜在的临床价值,可为临床提供一种新的检测手段。
Copeptin,as a stable surrogate biomarker for arginine vasopressin(AVP),plays an important role in the differential diagnosis of polyuria-polydipsia syndromes.Current guidelines recommend dynamic monitoring of copeptin levels during stimulation tests to assist in differentiating AVP deficiency(AVP-D)from primary polydipsia.Although these methods are well-established,they have certain limitations.Therefore,safer and more feasible stimulants with reliable effects are of clinical interest.Additionally,the currently available copeptin assay,which is based on time-resolved immunofluorescence assay,can be subject to interference from autoantibodies or hemolysis.This study aims to evaluate the effects of four common stimulants used in growth hormone function tests,namely levodopa,insulin,glucagon,and octreotide,on copeptin levels using a reliable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method developed in our laboratory.A total of 62 subjects undergoing growth hormone function tests were retrospectively enrolled and stratified by stimulation type:levodopa(n=28),insulin-induced hypoglycemia(n=7),glucagon(n=20),and octreotide(n=7).Blood samples were collected at baseline,30,60,90,and 120 min(for the glucagon stimulation test,samples were collected at 120 and 180 min)for growth hormone determination.Copeptin levels at each time point were measured using LC-MS/MS.The effects of stimulation and correlations were analyzed using the Wilcoxon paired signed-rank test,Mann-Whitney test,and Spearman correlation analysis.The results demonstrated that copeptin levels increased under levodopa stimulation by a maximum of 8.47-fold of baseline(p<0.0001),under insulin stimulation by a maximum of 5.85-fold of baseline(p=0.0312),under glucagon stimulation by a maximum of 1.43-fold of baseline(p<0.0001),and decreased under octreotide to 43%of baseline(p<0.05).No significant correlation was observed between copeptin level changes and those in growth hormone levels.In the levodopa-stimulation group,the maximum value of copeptin in patients with AVP deficiency was significantly lower than that in non-AVP deficiency patients(p=0.0002),and the area under the receiver operating characteristic curve was 0.98(95%confidence interval 0.94–1.00,p=0.0021).Our results demonstrate that levodopa and insulin can effectively stimulate copeptin secretion,whereas octreotide exhibits a suppressive effect.These findings offer important physiological insights into AVP regulation and indicate that certain GH stimulation agents may have extended utility in copeptin-based diagnostic strategies.The LC-MS/MS method for detecting copeptin has potential clinical value in the diagnosis of patients with AVP deficiency and can provide a new detection method for clinical practice.However,the relatively small sample sizes restrict the statistical power,and larger prospective studies are warranted.
作者
穆丹妮
齐志宏
马逸辰
高雨濛
李悦萌
张琪
禹松林
邱玲
程歆琦
MU Danni;QI Zhihong;MA Yichen;GAO Yumeng;LI Yuemeng;ZHANG Qi;YU Songlin;QIU Ling;CHENG Xinqi(Department of Laboratory Medicine,Peking Union Medical College Hospital,Peking Union Medical College&Chinese Academy of Medical Science,Beijing 100730,China)
出处
《色谱》
北大核心
2026年第3期302-311,共10页
Chinese Journal of Chromatography
基金
四大慢病重大专项(2024ZD0533200,2024ZD0533205)
国家重点研发计划项目(2022YFC3602302)。
关键词
液相色谱-串联质谱
和肽素
精氨酸加压素
精氨酸加压素缺乏症
生长激素功能试验
liquid chromatography-tandem mass spectrometry
copeptin,arginine vasopressin
arginine vasopressin deficiency
growth hormone function test
