This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Henley, D. E. Articles by Lightman, S. L. PubMed PubMed Citation Articles by Henley, D. E. Articles by Lightman, S. L. Related Collections Adrenal and Hypertension Neuroendocrinology and Pituitary

Hypothalamic-Pituitary-Adrenal Axis Activation in Obstructive Sleep Apnea: The Effect of Continuous Positive Airway Pressure Therapy

Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (D.E.H., G.M.R., J.A.D., S.A.W., S.L.L.), University of Bristol, Bristol BS1 3NY, United Kingdom; Faculty of Medicine, Dentistry, and Health Sciences (D.E.H.), University of Western Australia, Perth 6009, Western Australia; and Departments of Respiratory Medicine (F.B., R.G., J.R.C.) and Clinical Biochemistry (W.W.W.), University Hospitals Bristol, Bristol BS1 3NU, United Kingdom

Address all correspondence and requests for reprints to: Dr. David E. Henley, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, 1st Floor, C-Block, Hospital Avenue, Nedlands WA 6009, Australia. E-mail: dhenley{at}cygnus.uwa.edu.au.

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.