INCREASED FREE CORTISOL IN PLASMA OF DOGS WITH PORTOSYSTEMIC ENCEPHALOPATHY (PSE)

Dogs with portosystemic encephalopathy (PSE) are known to develop pitu itary-dependent hyperadrenocorticism, but there have been no reports o n the plasma protein binding of cortisol in these dogs. Since the live r is involved in the synthesis of corticosteroid-binding globulin (CBG ) and other transport proteins for cortisol, the binding characteristi cs 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 fo und 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, respective ly). 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 significa ntly correlated with the concentration of albumin or the total cortiso l in plasma. We conclude that there is decreased binding of cortisol i n plasma of dogs with PSE due to decreased hepatic synthesis of cortis ol binding proteins. The presence of increased concentrations of free cortisol in these dogs indicates that their basal pituitary-adrenocort ical activity was increased, probably due to aberrant neurotransmissio n in brain centers associated with pituitary function, as a result of hepatic encephalopathy.