Department of Pulmonology and Critical Care Medicine, Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Gwangju, Republic of Korea.
Chronobiol Int. 2012 Oct;29(8):1109-20. doi: 10.3109/07420528.2012.706767. Epub 2012 Aug 13.
A flatter diurnal rhythm of cortisol has been reported to be associated with early mortality in patients with metastatic breast cancer. The clinical stage of disease at the time of diagnosis and the patient's performance status (PS) are known to be important prognostic factors for lung cancer (LC) survival. The authors examined the relationship between diurnal cortisol rhythms and these prognostic factors in patients with advanced LC. Cortisol concentrations were measured in saliva samples collected from 52 patients (37 males/15 females) with advanced LC and from 56 healthy subjects (32 males/24 females) to characterize the diurnal cortisol rhythm, specifically the cortisol awakening response (CAR) and diurnal cortisol decline (DCD). Variations of CAR and DCD in the patients were analyzed according to their clinical disease stage and PS score, and the differences in CAR and DCD between patients and healthy controls were compared. The patient group showed significantly reduced diurnal cortisol secretory activity and rhythmicity, compared with healthy controls. When the patients were subgrouped according to their clinical disease stage, patients with stage 4 disease showed significantly reduced CAR and flatter DCD compared with the healthy controls. However, the CAR and DCD in patients with stage 3a and 3b disease were comparable to those of healthy controls. Neither the CAR nor the DCD showed stepwise changes as the disease stage worsened. When patients were subgrouped according to their Eastern Cooperative Oncology Group (ECOG) PS score, there was stepwise reduction in the CAR and flattening of the DCD as the PS score increased. Both an abolished CAR and a flattened DCD were common in patients with ECOG PS scores of 3 and 4. These results indicate that alteration of the diurnal cortisol rhythm in patients with advanced LC is more closely associated with their PS score than with their clinical disease stage. Gradual alteration of the CAR and DCD, indicative of loss of 24-h cortisol rhythm, in concert with increase in PS score implies that endogenous circadian rhythms may also be disintegrating as the PS score worsens in these patients.
已有研究报道，皮质醇的昼夜节律变平与转移性乳腺癌患者的早期死亡率相关。疾病的临床分期和患者的体能状态（PS）是肺癌（LC）生存的重要预后因素。作者研究了昼夜皮质醇节律与这些预后因素在晚期 LC 患者中的关系。作者测量了 52 例晚期 LC 患者（37 例男性/15 例女性）和 56 例健康对照者（32 例男性/24 例女性）唾液样本中的皮质醇浓度，以描绘昼夜皮质醇节律，特别是皮质醇觉醒反应（CAR）和昼夜皮质醇下降（DCD）。根据患者的临床疾病分期和 PS 评分分析 CAR 和 DCD 的变化，并比较患者与健康对照组之间的 CAR 和 DCD 差异。与健康对照组相比，患者组的昼夜皮质醇分泌活性和节律性明显降低。当根据临床疾病分期对患者进行亚组分析时，与健康对照组相比，IV 期疾病患者的 CAR 明显降低且 DCD 更平坦。然而，IIIa 和 IIIb 期疾病患者的 CAR 和 DCD 与健康对照组相当。随着疾病分期恶化，CAR 和 DCD 均未显示出阶梯式变化。当根据东部肿瘤协作组（ECOG）PS 评分对患者进行亚组分析时，随着 PS 评分的增加，CAR 逐渐降低，DCD 变平。ECOG PS 评分为 3 或 4 的患者中，CAR 消失和 DCD 变平均很常见。这些结果表明，晚期 LC 患者昼夜皮质醇节律的改变与 PS 评分比与临床疾病分期更密切相关。CAR 和 DCD 的逐渐改变，表明 24 小时皮质醇节律丧失，与 PS 评分增加一起表明，随着这些患者 PS 评分的恶化，内源性昼夜节律也可能瓦解。
