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Abstract：
BACKGROUND: Cirrhotic patients are susceptible to sepsis and critical illness-related corticosteroid insufficiency (CIRCI). Dehydroepiandrosterone sulfate (DHEAS) is a corticotropin-dependent adrenal androgen, which has immunostimulating and antiglucocorticoid effects. Considering the synchronized synthesis of cortisol and DHEAS and their opposing effects to each other, investigators have proposed measuring these two hormones as a ratio. Severe sepsis has been associated with low DHEAS, especially relative to high cortisol. Despite growing interest in the role of adrenal androgen replacement in critical illness, there have been no data about DHEAS and the DHEAS/cortisol ratio in patients with liver cirrhosis. We studied whether low concentrations of DHEAS and decreased DHEAS/cortisol ratio are associated with poor outcome in patients with liver cirrhosis and septic shock.
METHODS: We recruited 46 cirrhotic patients with septic shock, and 46 noncirrhotic counterparts matched by age and sex. We evaluated adrenal function using the short corticotropin stimulation test and analyzed the relation between DHEAS and cortisol.
RESULTS: While the nonsurvivors in the cirrhotic group had significantly lower baseline DHEAS, lower baseline DHEAS/cortisol ratio, and reduced increments of both DHEAS and cortisol upon corticotropin stimulation, the survivors had lower baseline cortisol. Cirrhotic patients with lower DHEAS/cortisol ratio (<1.50) had higher levels of interleukin-6 and tumor necrosis factor alpha, higher Sequential Organ Failure Assessment scores, and higher rates of CIRCI and hospital mortality. Using the area under the receiver operating characteristic (AUROC) curve, both DHEAS and the DHEAS/cortisol ratio demonstrated a good discriminative power for predicting hospital survival (AUROC 0.807 and 0.925 respectively). The cirrhotic group had lower DHEAS and DHEAS/cortisol ratio but higher rates of CIRCI and hospital mortality, compared to the noncirrhotic group.
CONCLUSIONS: There is dissociation between cortisol (increased) and DHEAS (decreased) in those cirrhotic patients who succumb to septic shock. Low DHEAS/cortisol ratios are associated with more severe diseases, inflammation, and CIRCI and can serve as a prognostic marker. More investigations are needed to evaluate the role of adrenal androgen in this clinical setting.
METHODS: We recruited 46 cirrhotic patients with septic shock, and 46 noncirrhotic counterparts matched by age and sex. We evaluated adrenal function using the short corticotropin stimulation test and analyzed the relation between DHEAS and cortisol.
RESULTS: While the nonsurvivors in the cirrhotic group had significantly lower baseline DHEAS, lower baseline DHEAS/cortisol ratio, and reduced increments of both DHEAS and cortisol upon corticotropin stimulation, the survivors had lower baseline cortisol. Cirrhotic patients with lower DHEAS/cortisol ratio (<1.50) had higher levels of interleukin-6 and tumor necrosis factor alpha, higher Sequential Organ Failure Assessment scores, and higher rates of CIRCI and hospital mortality. Using the area under the receiver operating characteristic (AUROC) curve, both DHEAS and the DHEAS/cortisol ratio demonstrated a good discriminative power for predicting hospital survival (AUROC 0.807 and 0.925 respectively). The cirrhotic group had lower DHEAS and DHEAS/cortisol ratio but higher rates of CIRCI and hospital mortality, compared to the noncirrhotic group.
CONCLUSIONS: There is dissociation between cortisol (increased) and DHEAS (decreased) in those cirrhotic patients who succumb to septic shock. Low DHEAS/cortisol ratios are associated with more severe diseases, inflammation, and CIRCI and can serve as a prognostic marker. More investigations are needed to evaluate the role of adrenal androgen in this clinical setting.
摘要：
背景：肝硬化患者易患脓毒症和危重病相关的皮质类固醇功能不全（CIRCI）。硫酸脱氢表雄酮（DHEAS）是一种促肾上腺皮质激素依赖性肾上腺雄激素，具有免疫刺激和抗糖皮质激素作用。考虑到皮质醇和DHEAS的同步合成及其相互相反的作用，研究人员建议测量这两种激素的比例。严重脓毒症与低DHEAS相关，特别是相对于高皮质醇。尽管人们对肾上腺雄激素替代在危重病中的作用越来越感兴趣，没有关于肝硬化患者DHEAS和DHEAS/皮质醇比值的数据。我们研究了低浓度的DHEAS和降低的DHEAS/皮质醇比率是否与肝硬化和感染性休克患者的不良预后相关。
方法：我们招募了46例肝硬化伴感染性休克患者，和46非肝硬化对应的年龄和性别相匹配。我们使用短促肾上腺皮质激素刺激试验评估了肾上腺功能，并分析了DHEAS与皮质醇之间的关系。
结果：虽然肝硬化组中的非幸存者的基线DHEAS明显较低，较低的基线DHEAS/皮质醇比，促肾上腺皮质激素刺激后DHEAS和皮质醇的增量减少，幸存者的基线皮质醇水平较低.DHEAS/皮质醇比值较低(<1.50)的肝硬化患者白细胞介素-6和肿瘤坏死因子α水平较高,更高的序贯器官衰竭评估分数，和更高的CIRCI和医院死亡率。使用接收器工作特征（AUROC）曲线下的面积，DHEAS和DHEAS/皮质醇比值均显示出良好的预测住院生存率的判别力(AUROC分别为0.807和0.925).肝硬化组的DHEAS和DHEAS/皮质醇比率较低，但CIRCI和医院死亡率较高，与非肝硬化组相比。
结论：在那些死于脓毒性休克的肝硬化患者中，皮质醇（增加）和DHEAS（减少）之间存在分离。低DHEAS/皮质醇比率与更严重的疾病相关，炎症,和CIRCI，可以作为预后标志物。需要更多的研究来评估肾上腺雄激素在这种临床环境中的作用。
方法：我们招募了46例肝硬化伴感染性休克患者，和46非肝硬化对应的年龄和性别相匹配。我们使用短促肾上腺皮质激素刺激试验评估了肾上腺功能，并分析了DHEAS与皮质醇之间的关系。
结果：虽然肝硬化组中的非幸存者的基线DHEAS明显较低，较低的基线DHEAS/皮质醇比，促肾上腺皮质激素刺激后DHEAS和皮质醇的增量减少，幸存者的基线皮质醇水平较低.DHEAS/皮质醇比值较低(<1.50)的肝硬化患者白细胞介素-6和肿瘤坏死因子α水平较高,更高的序贯器官衰竭评估分数，和更高的CIRCI和医院死亡率。使用接收器工作特征（AUROC）曲线下的面积，DHEAS和DHEAS/皮质醇比值均显示出良好的预测住院生存率的判别力(AUROC分别为0.807和0.925).肝硬化组的DHEAS和DHEAS/皮质醇比率较低，但CIRCI和医院死亡率较高，与非肝硬化组相比。
结论：在那些死于脓毒性休克的肝硬化患者中，皮质醇（增加）和DHEAS（减少）之间存在分离。低DHEAS/皮质醇比率与更严重的疾病相关，炎症,和CIRCI，可以作为预后标志物。需要更多的研究来评估肾上腺雄激素在这种临床环境中的作用。
