Increased free cortisol in plasma of dogs with portosystemic encephalopathy (PSE)

Dogs with portosystemic encephalopathy (PSE) are known to develop pituitary-dependent hyperadrenocorticism, but there have been no reports on the plasma protein binding of cortisol in these dogs. Since the liver is involved in the synthesis of corticosteroid-binding globulin (CBG) and other transport proteins for cortisol, the binding characteristics of these proteins and thus the biologically-active free fraction of cortisol might be altered in dogs with PSE. We investigated the total concentration of cortisol and the free fraction and the free cortisol concentration in plasma of thirty-two dogs with PSE due to inherited portosystemic shunts or chronic active hepatitis with cirrhosis. We found a significantly higher free fraction (14.7 +/- 5.8%, P < 0.0001) and free cortisol concentration (26.3 +/- 23.1 nM, P < 0.001) in these dogs than in healthy controls (8.2 +/- 2.3% and 9.2 +/- 7.2 nM, respectively). Moreover, basal concentrations of total cortisol in the dogs with PSE were higher than in the healthy controls (190 +/- 146 nM v. 107 +/- 65, P < 0.01). The per cent free cortisol in plasma was not significantly correlated with the concentration of albumin or the total cortisol in plasma. We conclude that there is decreased binding of cortisol in plasma of dogs with PSE due to decreased hepatic synthesis of cortisol binding proteins. The presence of increased concentrations of free cortisol in these dogs indicates that their basal pituitary-adrenocortical activity was increased, probably due to aberrant neurotransmission in brain centers associated with pituitary function, as a result of hepatic encephalopathy.