title: Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia.
abstract: The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycorticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hyporesponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsiveness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; irene.cortespuch@nih.gov.
authors.forename: Irene
authors.initials: I
authors.lastname: Cortés-Puch
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; Department of General Surgery, The Johns Hopkins Hospital, Baltimore, Maryland; National Institutes of Health Research Scholars Program, Howard Hughes Medical Institute, Chevy Chase, Maryland;
authors.forename: Caitlin W
authors.initials: CW
authors.lastname: Hicks
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland;
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland;
authors.forename: Steven B
authors.initials: SB
authors.lastname: Solomon
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland;
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
authors.affiliation: Medical Intensivist Program, Washington Hospital, Fremont, California;
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sweeney
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Development, National Institutes of Health, Bethesda, Maryland;
authors.forename: Lynnette K
authors.initials: LK
authors.lastname: Nieman
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa; and.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Whitley
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
authors.forename: Ellen N
authors.initials: EN
authors.lastname: Behrend
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland;
authors.forename: Charles
authors.initials: C
authors.lastname: Natanson
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland;
authors.forename: Robert L
authors.initials: RL
authors.lastname: Danner
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003907:Dexamethasone; D004283:Dog Diseases / Q000503:physiopathology*; D004285:Dogs; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008901:Mineralocorticoids / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011023:Pneumonia, Staphylococcal / Q000503:physiopathology / Q000662:veterinary; D018805:Sepsis / Q000503:physiopathology / Q000662:veterinary; D013203:Staphylococcal Infections / Q000503:physiopathology* / Q000662:veterinary*; D016019:Survival Analysis
chemical_list: D008901:Mineralocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: adrenal insufficiency; adrenocorticotropic hormone; aldosterone; corticosteroids; cortisol; sepsis; septic shock