Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom.
J Clin Endocrinol Metab. 2009 Nov;94(11):4234-42. doi: 10.1210/jc.2009-1174. Epub 2009 Oct 9.
Obstructive sleep apnea (OSA) is a common condition with significant cardiovascular and metabolic comorbidity. We hypothesized that these may result from OSA-induced perturbations of endogenous ultradian hypothalamic-pituitary-adrenal axis activity.
The aim of the study was to investigate ACTH and cortisol ultradian patterns using an automated, repetitive blood sampling technique.
Samples for ACTH and cortisol were collected from 10 patients with moderate to severe OSA under basal conditions, at 10-min intervals over 24 h, at diagnosis and 3 months after compliant continuous positive airway pressure (CPAP) therapy. Multiple-parameter deconvolution estimated specific measures of ACTH and cortisol pulsatile secretion from blood hormone concentrations.
Mean total ACTH and cortisol production were elevated pre-CPAP compared to post-CPAP (ACTH, 1459.8 +/- 123.0 vs. 808.1 +/- 97.9 pg/ml, P < 0.001; cortisol, 5748.9 +/- 364.9 vs. 3817.7 +/- 351.7 nmol/liter, P < 0.001) as were mean total pulsatile production (ACTH, 764.1 +/- 86.3 vs. 383.5 +/- 50.0 pg/ml, P = 0.002; cortisol, 4715.9 +/- 253.3 vs. 3227.7 +/- 258.8 nmol/liter, P < 0.001). ACTH and cortisol secretory burst mean half-duration were higher at diagnosis (12.3 +/- 0.7 and 13.5 +/- 0.7 vs. 7.8 +/- 0.4 and 8.4 +/- 0.6 min, respectively, P < 0.001); thus, 95% of each ACTH secretion occurred in 21.0 +/- 1.2 vs. 12.9 +/- 0.8 min post-CPAP (P < 0.001) and for cortisol in 23.0 +/- 1.2 vs. 14.2 +/- 1.1 min post-CPAP (P < 0.001). Approximate entropy (ApEn) revealed greater disorderliness in both ACTH (P = 0.03) and cortisol (P = 0.001) time series pre-CPAP. Forward and reverse cross-ApEn suggested nodal disruption at central and adrenal levels pre-CPAP (P = 0.01). Significantly elevated cortisol responses to a single breath of 35% CO(2) occurred pre-CPAP (P = 0.006).
Untreated compared to treated OSA is associated with marked disturbances in ACTH and cortisol secretory dynamics, resulting in prolonged tissue exposure to disordered, elevated hormone levels.
阻塞性睡眠呼吸暂停（OSA）是一种常见病症，伴有显著的心血管和代谢合并症。我们假设这些可能是由于 OSA 引起的内源性下丘脑-垂体-肾上腺轴活动的超低频波动所致。
本研究旨在使用自动、重复的采血技术研究 ACTH 和皮质醇的超低频模式。
在诊断时和接受依从性持续气道正压通气（CPAP）治疗 3 个月后，10 名中重度 OSA 患者在基础状态下，每隔 10 分钟采集一次 ACTH 和皮质醇样本，共采集 24 小时。多参数解卷积法从血液激素浓度中估计了特定的 ACTH 和皮质醇脉冲分泌指标。
与 CPAP 后相比，CPAP 前的平均总 ACTH 和皮质醇生成升高（ACTH，1459.8 ± 123.0 与 808.1 ± 97.9 pg/ml，P < 0.001；皮质醇，5748.9 ± 364.9 与 3817.7 ± 351.7 nmol/L，P < 0.001），平均总脉冲分泌也升高（ACTH，764.1 ± 86.3 与 383.5 ± 50.0 pg/ml，P = 0.002；皮质醇，4715.9 ± 253.3 与 3227.7 ± 258.8 nmol/L，P < 0.001）。ACTH 和皮质醇分泌爆发的平均半持续时间在诊断时更高（12.3 ± 0.7 和 13.5 ± 0.7 与 7.8 ± 0.4 和 8.4 ± 0.6 min，分别为 P < 0.001）；因此，95%的 ACTH 分泌发生在 CPAP 后 21.0 ± 1.2 与 12.9 ± 0.8 min 之间（P < 0.001），皮质醇分泌发生在 CPAP 后 23.0 ± 1.2 与 14.2 ± 1.1 min 之间（P < 0.001）。近似熵（ApEn）显示 CPAP 前 ACTH（P = 0.03）和皮质醇（P = 0.001）时间序列的无序性增加。前向和反向交叉 ApEn 提示 CPAP 前中枢和肾上腺水平的节点中断（P = 0.01）。CPAP 前单次吸入 35%CO2 引起的皮质醇反应显著升高（P = 0.006）。
与治疗 OSA 相比，未经治疗的 OSA 与 ACTH 和皮质醇分泌动力学的显著紊乱有关，导致组织长时间暴露于紊乱和升高的激素水平。
