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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. <\/jats:p>","DOI":"10.1152\/ajpendo.00345.2014","type":"journal-article","created":{"date-parts":[[2014,10,8]],"date-time":"2014-10-08T05:08:57Z","timestamp":1412744937000},"page":"E994-E1008","source":"Crossref","is-referenced-by-count":25,"title":["Hypothalamic-pituitary-adrenal axis in lethal canine <i>Staphylococcus aureus<\/i> pneumonia"],"prefix":"10.1152","volume":"307","author":[{"given":"Irene","family":"Cort\u00e9s-Puch","sequence":"first","affiliation":[{"name":"Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin W.","family":"Hicks","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, 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