Mineralocorticoid receptor function in posttraumatic stress disorder after pretreatment with metyrapone

Biol Psychiatry. 2006 Oct 1;60(7):784-7. doi: 10.1016/j.biopsych.2006.01.014. Epub 2006 Mar 29.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenocorticotropic Hormone / blood*
  • Adult
  • Analysis of Variance
  • Antimetabolites / pharmacology
  • Cortodoxone / blood
  • Feedback, Physiological / drug effects
  • Feedback, Physiological / physiology*
  • Female
  • Fludrocortisone / administration & dosage
  • Hormones / administration & dosage
  • Humans
  • Hydrocortisone / blood*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Matched-Pair Analysis
  • Metyrapone / pharmacology
  • Middle Aged
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiology
  • Pituitary-Adrenal System / physiopathology
  • Receptors, Mineralocorticoid / drug effects
  • Receptors, Mineralocorticoid / metabolism*
  • Reference Values
  • Stress Disorders, Post-Traumatic / drug therapy
  • Stress Disorders, Post-Traumatic / metabolism*

Substances

  • Antimetabolites
  • Hormones
  • Receptors, Mineralocorticoid
  • Adrenocorticotropic Hormone
  • Fludrocortisone
  • Cortodoxone
  • Hydrocortisone
  • Metyrapone