cosyntropin and Stress-Disorders--Post-Traumatic

Studies have demonstrated altered sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to its direct regulators in veterans with posttraumatic stress disorder (PTSD), but little is known about the adrenal response to hormonal stimulation in PTSD. An increased cortisol response to synthetic corticotropin-releasing factor (CRF) was recently found to be associated with war-zone deployment and not PTSD specifically. To more accurately assess whether there is altered adrenocortical responsivity to hormonal stimulation in relation to war-zone deployment or PTSD, we performed the low-dose cosyntropin stimulation test in a sample of 45 male veterans: 13 war-zone exposed veterans with chronic PTSD (PTSD+), 22 war-zone exposed veterans without chronic PTSD (PTSD-), and 10 veterans not exposed to a war-zone and without chronic PTSD (non-exposed). Plasma cortisol and ACTH were measured at baseline and at intervals over a one hour period following intravenous administration of 1μg of cosyntropin. A significant main effect of group (PTSD+, PTSD-, non-exposed) on the cortisol response to cosyntropin was observed. Cosyntropin-stimulated plasma cortisol levels were significantly higher in the PTSD+ and PTSD- groups compared to the non-exposed group. A significant main effect of group was also observed on peak cortisol levels. These findings suggest that war-zone exposure itself has persistent effects on adrenocortical activity.

Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cosyntropin; Dehydroepiandrosterone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Military Personnel; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Socioeconomic Factors; Stress Disorders, Post-Traumatic; Veterans

We recently found increased adrenal cortisol responses to adrenocorticotropic hormone (ACTH)1-24 and increased pituitary ACTH and adrenal cortisol responses to corticotropin-releasing factor in premenopausal women with chronic post-traumatic stress disorder (PTSD) compared to healthy nontraumatized subjects. This pattern of hypothalamic-pituitary-adrenal axis (HPA) hyper-reactivity has been previously seen in healthy individuals treated with the antiglucocorticoid mifepristone. We therefore investigated whether endogenous plasma levels of antiglucocorticoids such as dehydroepiandrosteroine (DHEA) and progesterone were increased in premenopausal women with PTSD at baseline or in response to adrenal activation by ACTH1-24. The study revealed that DHEA responses to 250 microg ACTH1-24 were increased in 13 PTSD subjects compared to 13 healthy nontraumatized subjects, while DHEA levels were generally increased in the PTSD subjects compared to seven healthy traumatized subjects. Cortisol responses to ACTH1-24 were also higher in the women with PTSD, while progesterone levels and responses were not different among the three groups. In addition, among the PTSD subjects, the peak change in DHEA in response to ACTH1-24 was negatively correlated with the total Clinician Administered PTSD Scale score, while the peak DHEA to cortisol ratio was inversely associated with negative mood symptoms measured by the Profile of Mood States scale. This work suggests that an increased capacity for DHEA release in response to extreme adrenal activation may influence the pattern of HPA axis adaptation to extreme stress, as well as mitigate the severity of PTSD and negative mood symptoms in premenopausal women with PTSD.

Topics: Adrenal Glands; Adult; Aging; Behavior; Cosyntropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estrogens; Female; Humans; Hydrocortisone; Menstrual Cycle; Mood Disorders; Progesterone; Psychiatric Status Rating Scales; Stress Disorders, Post-Traumatic

Early adverse life events may predispose individuals to the development of mood and anxiety disorders in adulthood, perhaps by inducing persistent changes in corticotropin-releasing factor (CRF) neuronal systems. The present study sought to evaluate pituitary-adrenal responses to standard hypothalamic-pituitary-adrenal axis challenge tests in adult female survivors of childhood abuse with and without major depressive disorder.. Plasma ACTH and cortisol responses to the administration of 1 microg/kg ovine CRF and plasma cortisol responses to the administration of 250 microg ACTH(1-24) were measured in healthy women without early life stress (N=20), women with childhood abuse without major depressive disorder (N=20), women with childhood abuse and major depressive disorder (N=15), and women with major depression but no early life stress (N=11).. Abused women without major depressive disorder exhibited greater than usual ACTH responses to CRF administration, whereas abused women with major depressive disorder and depressed women without early life stress demonstrated blunted ACTH responses. In the ACTH(1-24) stimulation test, abused women without major depressive disorder exhibited lower baseline and stimulated plasma cortisol concentrations. Abused women with comorbid depression more often suffered from posttraumatic stress disorder and reported more recent life stress than abused women without major depressive disorder.. These findings suggest sensitization of the anterior pituitary and counterregulative adaptation of the adrenal cortex in abused women without major depressive disorder. On subsequent stress exposure, women with a history of childhood abuse may hypersecrete CRF, resulting in down-regulation of adenohypophyseal CRF receptors and symptoms of depression and anxiety.

Topics: Adrenocorticotropic Hormone; Adult; Age Factors; Child; Child Abuse; Comorbidity; Corticotropin-Releasing Hormone; Cosyntropin; Depressive Disorder; Disease Susceptibility; Down-Regulation; Female; Humans; Hydrocortisone; Life Change Events; Pituitary Gland, Anterior; Receptors, Corticotropin-Releasing Hormone; Stress Disorders, Post-Traumatic; Survivors