Mineralocorticoid receptor function in posttraumatic stress disorder after pretreatment with metyrapone

Abstract

Background: Alterations of mineralocorticoid receptor (MR) mediated negative feedback inhibition of cortisol might contribute to abnormalities of hypothalamic-pituitary adrenal (HPA) activity in posttraumatic stress disorder (PTSD).

Methods: In a placebo-controlled study, we examined 11 subjects with PTSD and 11 healthy controls between 14:00 and 21:00. After pretreatment with 3 g metyrapone to inhibit basal endogenous cortisol secretion, subjects orally received in randomized order .5 mg of the MR agonist fludrocortisone or placebo. Adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were measured every 30 min until 21:00.

Results: Compared to placebo, fludrocortisone led to a significant decrease of ACTH and cortisol that was similar in both groups. Subjects with PTSD had higher raw cortisol and higher normed (baseline-related) ACTH and 11-deoxycortisol values after metyrapone independent of treatment with fludrocortisone or placebo.

Conclusions: While HPA responses after metyrapone seem to be stronger in PTSD compared to controls, no alterations of mineralocorticoid receptor function in PTSD were found in this study.