Cecal ligation and perforation is associated with adrenal insufficiency in rats

Abstract

There is renewed interest in the use of exogenous steroids to treat refractory hypotension in sepsis. Despite the growing body of literature demonstrating the efficacy of steroid therapy in this clinical setting, little is known regarding the mechanism responsible for the observed hypocortisolism. Scant data suggest that TNF inhibits the synthesis and secretion of cortisol by the adrenals. To investigate the pathophysiology of sepsis-induced adrenal insufficiency, we examined the adrenal response to an ACTH stimulation test in a rat model of gram-negative sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. Four hours following CLP, adrenal glands were removed, sectioned, and placed in incubation medium. ACTH stimulation tests were performed by the addition of cortrosyn and corticosterone levels measured at 0, 15, 30, and 60 min via radio-immunoassay. The results from CLP animals were compared to those of sham-operated, control rats. Cortrosyn stimulation of adrenal glands collected from control rats resulted in a 4- and 7-fold increase in corticosterone production over baseline at 30 and 60 min, respectively. However, adrenal glands collected from animals following CLP failed to respond to cortrosyn stimulation (Fig. 1) In conclusion, we have shown that cecal ligation and perforation is associated with a significant inhibition of the adrenocortical response to ACTH making this an excellent model to examine the pathophysiology of sepsis-induced adrenal insufficiency.