Department of Palliative Care and Rehabilitation Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
J Pain Symptom Manage. 2011 Apr;41(4):788-95. doi: 10.1016/j.jpainsymman.2010.06.021. Epub 2011 Jan 28.
Patients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patient's symptom burden.
To examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer.
A retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed.
The median age was 63 years (range 24-79), and 62% were men (n=48). Most patients had gastrointestinal (n=33, 43%) or thoracic (n=21, 27%) malignancies and were Caucasian (n=46, 60%). The median random cortisol level was 19.1 μg/dL (Q1-Q3, 13.4-23.8 [normal, 4.3-22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P=0.032) and symptoms including pain (0.50, P<0.001), fatigue (0.29, P=0.012), nausea (0.34, P=0.003), depression (0.24, P=0.032), and anxiety (0.25, P=0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n=28) was 20.6 μg/dL (Q1-Q3, 16.6-25.4) and significantly correlated with pain (0.55, P=0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥ 30 mg/day had a mean random cortisol level of 20.6 μg/dL (P=0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (-0.52, P=0.001).
In patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.
晚期癌症患者常出现疼痛、厌食和乏力等症状。阿片类药物治疗癌症疼痛可能导致神经激素功能障碍，从而加重患者的症状负担。
研究血清皮质醇和睾酮水平与癌症患者阿片类药物治疗和症状困扰之间的关系。
对 77 例因乏力或恶病质就诊的晚期癌症患者进行回顾性图表审查。我们收集了皮质醇水平（am 或随机）、睾酮水平（仅限男性）、吗啡等效日剂量（MEDD）和 Edmonton 症状评估量表测量的症状严重程度信息。进行了非参数相关分析。
中位年龄为 63 岁（范围 24-79），62%为男性（n=48）。大多数患者患有胃肠道（n=33，43%）或胸部（n=21，27%）恶性肿瘤，且为白种人（n=46，60%）。中位随机皮质醇水平为 19.1μg/dL（Q1-Q3，13.4-23.8[正常，4.3-22.4]），与 MEDD（Spearman 系数，0.25，P=0.032）和症状相关，包括疼痛（0.50，P<0.001）、乏力（0.29，P=0.012）、恶心（0.34，P=0.003）、抑郁（0.24，P=0.032）和焦虑（0.25，P=0.031）。经 Bonferroni 校正后，疼痛和恶心仍然具有统计学意义。经 Bonferroni 校正后，28 例晨皮质醇水平（n=28）中位值为 20.6μg/dL（Q1-Q3，16.6-25.4），与疼痛显著相关（0.55，P=0.003）。MEDD<30mg/天的患者平均随机皮质醇水平为 16.6μg/dL，而 MEDD≥30mg/天的患者平均随机皮质醇水平为 20.6μg/dL（P=0.01）。在 44 例患有癌症的男性患者中，MEDD 与总睾酮水平呈负相关（-0.52，P=0.001）。
在晚期癌症患者中，随机皮质醇水平升高与疼痛和阿片类药物使用相关，尽管皮质醇水平异常低的情况较为少见。接受更高阿片类药物治疗（MEDD>30）的患者皮质醇水平升高，男性患者的睾酮水平降低。我们的研究表明，晚期癌症患者的阿片类药物治疗可能抑制性腺功能，同时保留肾上腺轴。需要进一步研究。
