TY - JOUR
T1 - Pituitary response to metyrapone in Gulf War veterans
T2 - Relationship to deployment, PTSD and unexplained health symptoms
AU - Golier, Julia A.
AU - Schmeidler, James
AU - Yehuda, Rachel
N1 - Funding Information:
This work was supported by a VA/DoD and VA MERIT award to Dr. Golier and by a grant (5 M01 RR00071) for the Mount Sinai General Clinical Research Center from the National Institute of Health. The authors also gratefully acknowledge the time and effort of the veterans who participated in this study.
Funding Information:
Funding for this study was provided by a VA/Dod grant to Dr. Golier and an NIH Grant (5 M01 RR00071) to the Mount Sinai General Clinical Research Center; the VA, Dod and NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PY - 2009/10
Y1 - 2009/10
N2 - Objective: Gulf War deployment has been associated with a distinct neuroendocrine profile characterized by low 24 h basal ACTH levels and enhanced cortisol and ACTH suppression to low-dose dexamethasone. The metyrapone stimulation test was performed to further characterize hypothalamic-pituitary activity in Gulf War veterans (GWV) and its relationship to unexplained medical symptoms and post-traumatic stress disorder (PTSD). Method: Eleven GWV without PTSD, 18 GWV with PTSD and 15 healthy subjects not exposed to the Gulf War theater (non-exposed) underwent the metyrapone stimulation test, which inhibits cortisol synthesis, impairs cortisol-mediated negative feedback inhibition and in turn increases levels of ACTH and 11-deoxycortisol, a cortisol precursor. These hormones were measured at baseline (7:00 a.m.) and at intervals (from 8:00 a.m. to 4:00 p.m.) following the administration of metyrapone 750 mg orally at 7:05 a.m. and at 10:05 a.m. Results: There were group differences in the ACTH response despite similar cortisol and 11-deoxycortisol responses to metyrapone. GWV without PTSD had a significantly attenuated ACTH response compared to non-exposed subjects; GWV with PTSD had a significantly higher ACTH response than GWV without PTSD but did not differ from non-exposed subjects. Among GWV, unexplained medical health symptoms (e.g., neurological, musculoskeletal, cardiac, and pulmonary symptoms) and PTSD symptoms were significantly positively associated with the ACTH response to metyrapone. Conclusion: Gulf War deployment is associated with a substantially lower ACTH response to metyrapone. In contrast, unexplained health symptoms and PTSD in Gulf War veterans are associated with relatively greater hypothalamic-pituitary activity which may reflect increased CRF activity and is evident only in consideration of deployment effects. This pattern of differences suggests either that Gulf War deployment and its associated exposures results in enduring changes in pituitary function or that reduced hypothalamic-pituitary activity protects against the development of PTSD and other deployment-related health problems.
AB - Objective: Gulf War deployment has been associated with a distinct neuroendocrine profile characterized by low 24 h basal ACTH levels and enhanced cortisol and ACTH suppression to low-dose dexamethasone. The metyrapone stimulation test was performed to further characterize hypothalamic-pituitary activity in Gulf War veterans (GWV) and its relationship to unexplained medical symptoms and post-traumatic stress disorder (PTSD). Method: Eleven GWV without PTSD, 18 GWV with PTSD and 15 healthy subjects not exposed to the Gulf War theater (non-exposed) underwent the metyrapone stimulation test, which inhibits cortisol synthesis, impairs cortisol-mediated negative feedback inhibition and in turn increases levels of ACTH and 11-deoxycortisol, a cortisol precursor. These hormones were measured at baseline (7:00 a.m.) and at intervals (from 8:00 a.m. to 4:00 p.m.) following the administration of metyrapone 750 mg orally at 7:05 a.m. and at 10:05 a.m. Results: There were group differences in the ACTH response despite similar cortisol and 11-deoxycortisol responses to metyrapone. GWV without PTSD had a significantly attenuated ACTH response compared to non-exposed subjects; GWV with PTSD had a significantly higher ACTH response than GWV without PTSD but did not differ from non-exposed subjects. Among GWV, unexplained medical health symptoms (e.g., neurological, musculoskeletal, cardiac, and pulmonary symptoms) and PTSD symptoms were significantly positively associated with the ACTH response to metyrapone. Conclusion: Gulf War deployment is associated with a substantially lower ACTH response to metyrapone. In contrast, unexplained health symptoms and PTSD in Gulf War veterans are associated with relatively greater hypothalamic-pituitary activity which may reflect increased CRF activity and is evident only in consideration of deployment effects. This pattern of differences suggests either that Gulf War deployment and its associated exposures results in enduring changes in pituitary function or that reduced hypothalamic-pituitary activity protects against the development of PTSD and other deployment-related health problems.
KW - ACTH
KW - Cortisol
KW - Gulf War syndrome
KW - Medically unexplained illness
KW - Metyrapone
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=69849094099&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2009.04.004
DO - 10.1016/j.psyneuen.2009.04.004
M3 - Article
C2 - 19446401
AN - SCOPUS:69849094099
SN - 0306-4530
VL - 34
SP - 1338
EP - 1345
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 9
ER -