TY - JOUR
T1 - Hypothalamic-Pituitary-Adrenal Axis Activation in Obstructive Sleep Apnea : The Effect of Continuous Positive Airway Pressure Therapy
AU - Henley, D.E.
AU - Douthwaite, J.A.
AU - Wood, S.A.
AU - Buchanan, F.
AU - Gibson, R.
AU - Woltersdorf, W.W.
AU - Catterall, J.R.
AU - Lightman, S.L.
PY - 2009
Y1 - 2009
N2 - Context: 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. Objective: The aim of the study was to investigate ACTH and cortisol ultradian patterns using an automated, repetitive blood sampling technique. Design: 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. Results: 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% CO2 occurred pre-CPAP (P = 0.006). Conclusions: 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.
AB - Context: 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. Objective: The aim of the study was to investigate ACTH and cortisol ultradian patterns using an automated, repetitive blood sampling technique. Design: 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. Results: 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% CO2 occurred pre-CPAP (P = 0.006). Conclusions: 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.
U2 - 10.1210/jc.2009-1174
DO - 10.1210/jc.2009-1174
M3 - Article
C2 - 19820009
VL - 94
SP - 4234
EP - 4242
JO - Journal of Endocrinology & Metabolism
JF - Journal of Endocrinology & Metabolism
SN - 0021-972X
IS - 11
ER -