Glucocorticoid feedback sensitivity and adrenocortical responsiveness in posttraumatic stress disorder.
BACKGROUND
Decreased basal cortisol levels have been reported in individuals with posttraumatic stress disorder (PTSD). There is evidence for enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD, which could account for this, but other possible mechanisms have not been ruled out. We examined the HPA axis employing a metyrapone-cortisol infusion protocol designed to study negative feedback sensitivity.


METHODS
Vietnam combat trauma-exposed subjects met DSM-IV criteria for PTSD. Exclusion criteria included substance abuse and most medications. Endogenous feedback inhibition was removed by blocking cortisol synthesis with oral metyrapone and reintroduced by intravenous infusion of cortisol. In a placebo condition, subjects received oral placebo and normal saline infusion. Serial blood samples drawn over 4 hours were assayed for adrenocorticotrophic hormone (ACTH), cortisol, and 11-deoxycortisol. Selected samples were assayed for cortisol binding globulin (CBG) and dehydroepiandrosterone (DHEA).


RESULTS
Basal plasma cortisol was significantly decreased in PTSD subjects (n = 13) compared with control subjects (n = 16). No significant difference in the ACTH response to cortisol infusion following metyrapone was observed; however 11-deoxycortisol was significantly decreased in PTSD subjects. In addition, CBG was significantly increased in PTSD subjects, and DHEA was significantly decreased in both PTSD and combat-exposed control subjects.


CONCLUSIONS
These observations suggest decreased adrenocortical responsiveness may be an additional or alternative mechanism accounting for low cortisol in PTSD.
Kanter
E D
ED
Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98108, USA.
Wilkinson
C W
CW
Radant
A D
AD
Petrie
E C
EC
Dobie
D J
DJ
McFall
M E
ME
Peskind
E R
ER
Raskind
M A
MA
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism*; D005246:Feedback; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology* / Q000627:therapeutic use*; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000502:physiology; D011863:Radioimmunoassay; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism*
D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008797:Metyrapone