Chen Xu-Guang, Shi Sheng-Yi, Hu Lan, Chen Yu, Sun Han-Wen, Zhou Lei, Lu Zhen-Bing, Wang Huan, Wang Xiao-Shan, Yu Jie, Zhao Yu-Jia, Lu Yi-Ming, Ye Jing
Department of Geriatrics, Medical Center on Aging of Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Emergency Department of Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Neurol. 2022 Jul 27;13:946593. doi: 10.3389/fneur.2022.946593. eCollection 2022.
This study sought to improve methods to identify biomarkers in the neuroendocrine system related to stroke progression to improve the accuracy of traditional tools for evaluating stroke prognosis.
Seventy-four stroke patients and 237 healthy controls were prospectively included. We measured urinary epinephrine (E), noradrenaline (NE), dopamine (DA) and cortisol (F) on days 1, 3, and 5 after stroke onset and plasma F, adrenocorticotropic hormone (ACTH), thyrotropin (TSH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH). The correlation between these hormone levels and 90-day prognosis was analyzed, their value in assessing prognosis was compared with lesion volume and National Institutes of Health Stroke Scale (NIHSS) scores using receiver operating characteristic (ROC) curves, and their correlation with conventional clinical variables was assessed.
Levels of F, 24-h urinary free cortisol(UFC), E, NE, DA, and GH on days 1, 3, and 5 were significantly higher in stroke patients than in controls ( < 0.01), while ACTH and TSH decreased, gradually approaching normal within 5 days of onset. Levels of E, NE, F, and 24-h UFC were proportional to severity, and all gradually decreased within 5 days of onset in patients with a good prognosis and gradually increased or remained high in those with a poor prognosis. After adjustment for age, sex, NIHSS, or Glasgow Coma Scale (GCS) score, > 13.6 μg/dL, ACTH > 22.02 pg/mL and NE > 123.5 μg/ 24 h were identified as risk factors for a poor prognosis 90 days after stroke ( < 0.05). The combination of F, ACTH, NE, white blood cell count (WBC), glucose (Glu), and hemoglobin (Hb) was significantly more accurate than lesion volume (AUC: 0.931 vs. 0.694 = 0.019) and NIHSS score (AUC: 0.931 vs. 0.746 = 0.034) in predicting poor prognosis of stroke 1 day after onset. Hormones and traditional clinical variables were correlated to varying degrees, with NE correlating most strongly with 24-h UFC ( = 0.54) and moderately positively with lesion volume ( = 0.40) and NIHSS score ( = 0.45).
Stroke causes significant time-phased dynamic changes in the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, and plasma F, ACTH, and urinary NE levels can be used to assess stroke severity and prognosis.
Registration Number: ChiCTR1900024992. Registration Date: 2019/8/6.
本研究旨在改进识别神经内分泌系统中与卒中进展相关生物标志物的方法，以提高传统卒中预后评估工具的准确性。
前瞻性纳入74例卒中患者和237例健康对照。在卒中发病后第1、3和5天，我们测量了尿肾上腺素（E）、去甲肾上腺素（NE）、多巴胺（DA）和皮质醇（F），以及血浆F、促肾上腺皮质激素（ACTH）、促甲状腺激素（TSH）、催乳素（PRL）、促卵泡生成素（FSH）、促黄体生成素（LH）和生长激素（GH）。分析了这些激素水平与90天预后的相关性，使用受试者工作特征（ROC）曲线将它们在评估预后中的价值与病变体积和美国国立卫生研究院卒中量表（NIHSS）评分进行比较，并评估它们与传统临床变量的相关性。
卒中患者在第1、3和5天的F、24小时尿游离皮质醇（UFC）、E、NE、DA和GH水平显著高于对照组（<0.01），而ACTH和TSH降低，发病后5天内逐渐接近正常。E、NE、F和24小时UFC水平与严重程度成正比，在预后良好的患者中，发病后5天内均逐渐下降，而在预后不良的患者中逐渐升高或保持高位。在调整年龄、性别、NIHSS或格拉斯哥昏迷量表（GCS）评分后，F>13.6μg/dL、ACTH>22.02pg/mL和NE>123.5μg/24h被确定为卒中后90天预后不良的危险因素（<0.05）。在预测发病后1天的卒中预后不良方面，F、ACTH、NE、白细胞计数（WBC）、血糖（Glu）和血红蛋白（Hb）的组合显著比病变体积（AUC：0.931对0.694，P=0.019）和NIHSS评分（AUC：0.931对0.746，P=0.034）更准确。激素与传统临床变量存在不同程度的相关性，其中NE与24小时UFC相关性最强（r=0.54），与病变体积（r=0.40）和NIHSS评分（r=0.45）呈中度正相关。
卒中导致下丘脑-垂体-肾上腺轴和交感神经系统发生显著的时间阶段性动态变化，血浆F、ACTH和尿NE水平可用于评估卒中严重程度和预后。
注册号：ChiCTR1900024992。注册日期：2019/8/6。
