Serum Free Cortisol Fraction in Healthy and Septic Neonatal Foals

Background: Relative cortisol insufficiency occurs in septic foals and impacts survival. Serum free (biologically available) cortisol concentration might be a better indicator of physiologic cortisol status than serum total cortisol concentration in foals. Hypotheses: In septic foals, (1) low free cortisol concentration correlates with disease severity and survival and (2) predicts disease severity and outcome better than total cortisol concentration. Animals: Fifty-one septic foals; 11 healthy foals; 6 healthy horses. Methods: In this prospective clinical study, foals meeting criteria for sepsis at admission were enrolled. University-owned animals served as healthy controls. Basal and cosyntropin-stimulated total cortisol concentration and percent free cortisol (% free cortisol) were determined by chemiluminescent immunoassay and ultrafiltration/ligand-binding methods, respectively. Group data were compared by ANOVA, Mann-Whitney U-tests, and receiver operator characteristic curves. Significance was set at P <.05. Results: Basal % free cortisol was highest in healthy foals at birth (58±8% mean±SD), and was higher (P≤.004) in healthy foals of all ages (33±6 to 58±8%) than in adult horses (7±3%). Cosyntropin-stimulated total and free cortisol concentrations were lower (P≤.03) in foals with shock (total = 6.2±8.1μg/dL; free = 3.5±4.8μg/dL versus total = 10.8±6.0μg/dL; free = 6.9±3.3μg/dL in foals without shock) and in nonsurvivors (total = 3.8±6.9μg/dL; free = 1.9±3.9μg/dL versus total = 9.1±7.7μg/dL; free = 5.5±4.4μg/dL in survivors). Free cortisol was no better than total cortisol at predicting disease severity or outcome in septic foals. Conclusions and Clinical Importance: Serum free cortisol is impacted by age and illness in the horse. There is no advantage to measuring free over total cortisol in septic foals.