Mineralocorticoid receptor function in posttraumatic stress disorder after pretreatment with metyrapone.
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.
Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany. otte@uke.uni-hamburg.de
Christian
C
Otte
Christoph
C
Muhtz
Sima
S
Daneshkhah
Alexander
A
Yassouridis
Falk
F
Kiefer
Klaus
K
Wiedemann
Michael
M
Kellner
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000704:Analysis of Variance; D000963:Antimetabolites / Q000494:pharmacology; D003350:Cortodoxone / Q000097:blood; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005438:Fludrocortisone / Q000008:administration & dosage; D006728:Hormones / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D016555:Matched-Pair Analysis; D008797:Metyrapone / Q000494:pharmacology; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000378:metabolism*
D000963:Antimetabolites; D006728:Hormones; D018161:Receptors, Mineralocorticoid; D000324:Adrenocorticotropic Hormone; D005438:Fludrocortisone; D003350:Cortodoxone; D006854:Hydrocortisone; D008797:Metyrapone