INCREASED PITUITARY ACTIVATION FOLLOWING METYRAPONE ADMINISTRATION INPOSTTRAUMATIC-STRESS-DISORDER

Our previous findings have demonstrated that individuals with post-tra umatic stress disorder (PTSD) show lower basal cortisol levels, a larg er number of lymphocyte glucocorticoid receptors, and an enhanced supp ression of cortisol following the administration of dexamethasone comp ared to normals and patients with major depression. We have previously suggested that these alterations reflect an enhanced negative feedbac k inhibition of the hypothalamic-pituitary-adrenal (HA) axis in PTSD. However, in the absence of direct knowledge of pituitary capability in this disorder, it has been equally likely that the alterations observ ed reflected either pituitary or adrenal insufficiency. In the present study, we examined ACTH release from the pituitary gland in PTSD foll owing the administration of metyrapone. Metyrapone resulted in a signi ficantly greater increase of ACTH and 11-deoxycortisol in combat veter ans with PTSD (n = 11) compared with normal male volunteers (n = 8). W hen seen in the context of other abnormalities observed in PTSD, the p resent demonstration of increased pituitary activity in the absence of negative feedback provides unequivocal support for the hypothesis of enhanced negative feedback.