Endocrine Abstracts

Background: Human chronotypes can be defined as the natural preference for specific wake and sleep times, as measured by the start and end of sleep on days without temporal restrictions. They are a consequence of the circadian clock individual periods. Cortisol is a key mediator for the rhythmic expression of circadian signals in almost all tissues. Physiological timing of cortisol levels is strictly regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Diseases affecting HPA signaling might therefore have important consequences on the individual’s chronotype. We therefore investigated patients with primary adrenal insufficiency with stable hydrocortisone replacement therapy.

Methods: In this exploratory pilot study, 20 patients with autoimmune adrenilitis and 40 control subjects of comparable age (54.53±18.42 vs 48.56±15.5 years) and sex (14f/6m vs 32f/8m) were assessed for their chronotypes using the Munich Chronotype Questionnaire for at least four times. They were also requested to constantly wear an actimetry device for 12 weeks, that monitored their sleep, temperature and light reception in this time frame. F-tests were applied to test for variability in sleep parameters and chronotypes between patients and controls, and a one-way ANOVA was applied to test for significant difference between means of sleep onset of the two cohorts.

Results: We observed high variability in sleep onset (F statistic =1.876, P <0.001) and sleep duration (F statistic =2.496, P <0.001) for patients in comparison to controls. The mean value for sleep onset were also observed to be earlier for patients (mean = 131.708 minutes) in comparison to controls (mean = 155.803 minutes) (confirmed with one way ANOVA, statistic=29.842, P <0.001). Chronotypes of patients showed high variability in comparison to controls (F statistic =2.192, P=0.008). In addition, the patient population also seemed to show a numerically later sleep onset on the weekends, which is not compensated by increased duration of sleep on the next day.

Discussion: The changes in chronotype and sleep onset in patients with primary adrenal insufficiency are likely caused by glucocorticoid replacement and possibly additional hormonal alterations. Improved awareness of their sleep variability and more controlled sleep/wake schedules, as well as illumination can likely improve the patients’ life quality. Possibly associated clinically relevant effects on cardiovascular risk factors remains to be investigated in future experiments.