Hypothalamic-pituitary-adrenal axis activation in obstructive sleep apnea: the effect of continuous positive airway pressure therapy.
BACKGROUND
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.


METHODS
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% CO(2) 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.
Henley
David E
DE
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom. dhenley@cygnus.uwa.edu.au
Russell
Georgina M
GM
Douthwaite
Jennie A
JA
Wood
Susan A
SA
Buchanan
Fiona
F
Gibson
Rosemary
R
Woltersdorf
Wolfram W
WW
Catterall
James R
JR
Lightman
Stafford L
SL
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008875:Middle Aged; D010349:Patient Compliance; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012891:Sleep Apnea Syndromes / Q000503:physiopathology* / Q000628:therapy*; D049629:Waist-Hip Ratio
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone