Allende Santiago, Medina Johnna L, Spiegel David, Zeitzer Jamie M
PGSP-Stanford Psy.D. Consortium, Palo Alto University, 1791 Arastradero Road, Palo Alto, CA 94304, United States.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road Stanford, CA 94305-5717, United States.
Psychoneuroendocrinology. 2020 May;115:104648. doi: 10.1016/j.psyneuen.2020.104648. Epub 2020 Mar 8.
Flattened diurnal salivary cortisol patterns predict shorter subsequent survival with breast, lung, and renal cell carcinomas. The underlying cause of this flattened slope is undetermined, though it has been hypothesized to be secondary to a deficit in the amplitude of the circadian clock. To gain greater insight into the portions of the diurnal salivary curve that are associated with cancer survival, we examined (1) which points in the diurnal curve are predictive of the slope of the curve and (2) whether elevated evening cortisol levels alone are associated with reduced HPA-axis feedback inhibition (i.e., decreased sensitivity to the dexamethasone suppression test).
We examined study hypotheses on adult women with advanced breast cancer (age = 54.3 ± 9.58 years; n = 99) using non-parametric Wilcoxon's rank-sum tests, Spearman correlation coefficients and an accuracy formula based on a confusion matrix. Cortisol was sampled five times per day for three consecutive days, with dexamethasone administered late on the second day.
Salivary cortisol concentrations did not vary between those with flat and steep slopes during the morning (p's > .05), but did vary in the evening (p's < 0.05). Furthermore, the concentration of the 2100h alone was 86% accurate in discriminating between individuals classified as having "flat" or "steep" slopes. Dexamethasone suppression was only associated with diurnal salivary cortisol slope (p = .0042).
Evening cortisol levels are a sensitive indicator flattened diurnal cortisol slope, suggesting evening cortisol may also be a useful predictor of breast cancer survival. Future research should focus on determining the causes of abnormally increased evening cortisol.
昼夜唾液皮质醇水平模式变平预示着随后乳腺癌、肺癌和肾细胞癌患者的生存期更短。尽管有人推测这种变平的斜率是昼夜节律钟振幅不足的继发结果，但这种变平斜率的根本原因尚未确定。为了更深入了解昼夜唾液曲线中与癌症生存期相关的部分，我们研究了：（1）昼夜曲线中的哪些点可预测曲线斜率；（2）仅夜间皮质醇水平升高是否与下丘脑-垂体-肾上腺（HPA）轴反馈抑制减弱（即对地塞米松抑制试验的敏感性降低）有关。
我们使用非参数威尔科克森秩和检验、斯皮尔曼相关系数以及基于混淆矩阵的准确性公式，对患有晚期乳腺癌的成年女性（年龄=54.3±9.58岁；n=99）的研究假设进行了检验。连续三天每天采集五次唾液皮质醇样本，第二天晚些时候给予地塞米松。
晨间唾液皮质醇浓度在斜率平缓组和斜率陡峭组之间没有差异（p值>.05），但夜间有差异（p值<0.05）。此外，仅21:00时的皮质醇浓度在区分被归类为“平缓”或“陡峭”斜率的个体时，准确率为86%。地塞米松抑制仅与昼夜唾液皮质醇斜率相关（p=.0042）。
夜间皮质醇水平是昼夜皮质醇斜率变平的敏感指标，表明夜间皮质醇也可能是乳腺癌生存期的有用预测指标。未来的研究应侧重于确定夜间皮质醇异常升高的原因。
