Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia

Irene Cortés-Puch, Caitlin W. Hicks, Junfeng Sun, Steven B. Solomon, Peter Q. Eichacker, Daniel A. Sweeney, Lynnette K. Nieman, Elizabeth M. Whitley, Ellen N. Behrend, Charles Natanson, Robert L. Danner

Research output: Contribution to journalArticle


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 desoxycor-ticosterone, 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 hypore-sponsiveness 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 unresponsive-ness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.

Original languageEnglish (US)
Pages (from-to)E994-E1008
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number11
StatePublished - Dec 1 2014



  • Adrenal insufficiency
  • Adrenocorticotropic hormone
  • Aldosterone
  • Corticosteroids
  • Cortisol
  • Sepsis
  • Septic shock

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Cortés-Puch, I., Hicks, C. W., Sun, J., Solomon, S. B., Eichacker, P. Q., Sweeney, D. A., Nieman, L. K., Whitley, E. M., Behrend, E. N., Natanson, C., & Danner, R. L. (2014). Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia. American Journal of Physiology - Endocrinology and Metabolism, 307(11), E994-E1008. https://doi.org/10.1152/ajpendo.00345.2014