Overnight suppression of HPA axis after mineraolocorticoid receptor stimulation: A sleep endocrine study

Nocturnal hyperactivity of hypothalamic-pituitary-adrenal axis (HPA) indicates decreased feedback inhibition with stress-related conditions such as major depression and sleep disorders. To characterize the role of mineralocorticoid (MR) in regulation of HPA axis activity during nocturnal sleep and involvement in sleep architecture, we investigated sleep endocrine effects of the MR agonist fludrocortisone in healthy men after pretreatment with metyrapone to minimize the impact of endogenous cortisol. Subjects (n=8) were treated on three occasions in a single-blinded design in random order with a) metyrapone, b) fludrocortisone after metyrapone, and c) placebo. Polysomnography was recorded and blood samples were drawn for determination of adrenocorticotropic hormone (ACTH) and cortisol during the entire night. After metyrapone administration ACTH was significantly enhanced, while overall nocturnal cortisol secretion remained largely unchanged. Whereas administration of fludrocortisone induced a significant inhibitory effect on basal ACTH and cortisol secretion, no considerable effects on sleep pattern were detectable. While the involvement of MR in sleep regulation needs further study, endocrine findings underline the role of MR in tonic regulation of HPA axis during nocturnal sleep and demonstrate the ability of fludrocortisone to further suppress HPA axis activity overnight. Additional studies would be required to evaluate endocrine and clinical fludrocortisone effects in depressive patients showing HPA hyperactivity.