Rhythms of pituitary-adrenal activity during sleep in patients with Cushing's disease

Previous studies have indicated a dependence of nocturnal pituitary-adrenal secretory activity on central nervous sleep processes in healthy humans: Under normal physiological conditions the release of ACTH/cortisol is inhibited during early sleep and becomes entrained to periods of NonREM sleep during late sleep. Here, we compared nocturnal dynamics in plasma concentrations of ACTH/cortisol in 7 patients with Cushing's disease with those of 7 healthy controls matched in age and sex with the patients. The patients in part were repeatedly tested. The total of 13 nights is composed of 7 nights of hyperpulsatile secretion pattern (5 patients) and 6 nights from hypopulsatile secretion pattern (4 patients). After an adaptation night polysomnographic sleep recordings were obtained and blood was sampled every 15 min between 23.00 and 7.00 h. Controls displayed the typical minimum in ACTH/cortisol concentrations during the early part of the night and maximum concentrations during the late part of the night, whereas ACTH/cortisol levels of Cushing patients indicated a relatively constant elevated pituitary-adrenal activity throughout the night, lacking any circadian variation. Autocorrelation functions revealed the presence of cortisol secretory rhythms with a similar period length in healthy controls (155.6+/-17.4 min) and patients with a hyperpulsatile pattern (142.4+/-6.6 min). In patients displaying hypopulsatility, no significant rhythmicity was observed. However, regardless of the type of secretory pulsatility, adrenal secretory activity started predominantly during periods of NonREM sleep (p<0.01) in healthy controls as well as in patients with Cushing's disease. This data indicates that the normal nocturnal circadian oscillation of pituitary-adrenal activity is absent in Cushing patients, whereas a link between pituitary-adrenal activity and ultradian rhythms of sleep appears to be preserved.