Glucocorticoid Metabolism in Critically Ill Dogs (Canis lupus familiaris)

Alisdair Boag, Andrew Brown, Amy M Koenigshof, Natalie Homer, Karen Sooy, Pauline Jamieson

Research output: Contribution to journalArticlepeer-review

Abstract

Critical illness due to sepsis is a major global health concern associated with a high burden of both mortality and cost. Glucocorticoid dysregulation in human sepsis is associated with poorer outcomes. This study examines glucocorticoid metabolism in septic canine patients to delineate elements of cellular dysregulation in common with critically ill humans and explore potential differences. This was a prospective case-control study conducted in the veterinary specialist critical care departments of two University teaching hospitals. Critically ill canine patients with naturally occurring sepsis or septic shock were compared to an in-hospital control population. Serum total, bound and free cortisol concentrations were increased in septic shock (p <0.001) and higher bound cortisol was associated with non-survival (p = 0.026). Urinary Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS) was performed to assess urinary glucocorticoid metabolites and estimate intracellular glucocorticoid metabolism. Decreased renal 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity inferred from increased urinary cortisol:cortisone ratio was observed in critically ill dogs (p <0.001). Decreased 11βHSD2 activity (p = 0.019) and increased A-ring reduction of cortisone (p = 0.001) were associated with non-survival within the critically ill dogs. Intriguingly, two dogs were identified with low circulating total cortisol (<2 mg/dL) associated with increased A-ring reduction of cortisol, not previously described. Investigation of spontaneous canine sepsis and septic shock reveals dysregulation of cortisol to cortisone conversion similar to that observed in human patients, but with differences in A-ring reduction compared to those reported in humans. Additionally, two dogs with high levels of cortisol inactivation associated with low circulating cortisol concentrations were identified.
Original languageEnglish
JournalDomestic Animal Endocrinology
Early online date23 Jan 2020
DOIs
Publication statusE-pub ahead of print - 23 Jan 2020

Keywords

  • cortisol
  • 11beta-hydroxysteroid dehydrogenase
  • critical illness
  • Canis lupus familiaris
  • CIRCI
  • A-ring reduction

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