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.

• Authors: Christian Otte, Christoph Muhtz, Sima Daneshkhah, Alexander Yassouridis, Falk Kiefer, Klaus Wiedemann, Michael Kellner
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 60 Issue 7 Pg. 784-7 (Oct 01 2006) ISSN: 0006-3223 [Print] United States
• PMID: 16566900 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

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