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Background: Hypothalamic-pituitary-adrenal (HPA) axis function is dynamic in the neonatal foal. The paired low dose/ high dose cosyntropin (ACTH) stimulation test allows comprehensive HPA axis assessment, but has not been evaluated in neonatal foals.Hypothesis: Foal age will significantly affect cortisol responses to a paired 10 and 100 mg dose cosyntropin stimulation test in healthy neonatal foals.Animals: Twenty healthy neonatal foals.Methods: HPA axis function was assessed in 12 foals at birth and at 12-24, 36-48 hours, and 5-7 days of age. At each age, basal cortisol and ACTH concentrations were measured and cortisol responses to 10 and 100 mg cosyntropin were assessed with a paired ACTH stimulation test protocol. Eight additional 36-48-hour-old foals received saline instead of 10 mg cosyntropin in the same-paired ACTH stimulation test design.Results: At birth, foals had significantly higher basal cortisol and ACTH concentrations and higher basal ACTH : cortisol ratios compared with foals in all other age groups. A significant cortisol response to both the 10 and 100 mg doses of cosyntropin was observed in all foals. The magnitude of the cortisol response to both doses of cosyntropin was significantly different across age groups, with the most marked responses in younger foals. There was no effect of the paired ACTH stimulation test design itself on cortisol responses.Conclusions and Clinical Importance: A paired 10 and 100 mg cosyntropin stimulation test can be used to evaluate HPA axis function in neonatal foals. Consideration of foal age is important in interpretation of HPA axis assessment.

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 o .05.Results: Basal % free cortisol was highest in healthy foals at birth (58AE8% meanAESD), and was higher (P .004) in healthy foals of all ages (33AE6 to 58AE8%) than in adult horses (7AE3%). Cosyntropin-stimulated total and free cortisol concentrations were lower (P .03) in foals with shock (total 5 6.2AE8.1 mg/dL; free 5 3.5AE4.8 mg/dL versus total 5 10.8AE6.0 mg/dL; free 5 6.9AE3.3 mg/dL in foals without shock) and in nonsurvivors (total 5 3.8AE6.9 mg/dL; free 5 1.9AE3.9 mg/dL versus total 5 9.1AE7.7 mg/dL; free 5 5.5AE4.4 mg/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.

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Background: Cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation tests are used to evaluate adrenal function. Low-dose ACTH stimulation tests are the most accurate method for diagnosing relative adrenal insufficiency in critically ill humans but have not been evaluated in foals.Hypothesis: Peak serum cortisol concentrations in healthy foals will not be significantly different after intravenous administration of 1, 10, 100, and 250 mg of cosyntropin.Animals: 14 healthy neonatal foals, 3-4 days of age. Methods: A randomized cross-over model was used in which cosyntropin (1, 10, 100, or 250 mg) was administered intravenously on days 3 and 4 of life. Blood samples were collected before and 30, 60, 90, 120, and 150 minutes after administration of cosyntropin for determination of serum cortisol concentration.Results: Serum cortisol concentrations did not significantly increase after administration of 1 mg of cosyntropin. Cortisol concentration peaked 30 minutes after administration of 10 mg of cosyntropin and 90 minutes after 100 and 250 mg of cosyntropin. There was no relationship between cosyntropin dose and serum cortisol concentration at 30 minutes. Compared with the 10-mg dose, 100 and 250 mg of cosyntropin induced significantly greater cortisol concentrations at 90 minutes, at which point the 10-mg cosyntropin-dose cortisol values were indistinguishable from baseline. There was no significant difference in the area under the cortisol concentration curve between the 100-and 250-mg doses. No effect of day of testing or foal weight on peak cortisol concentration was detected.Conclusions and Clinical Importance: The results of this study suggest that 10-and 100-mg doses of cosyntropin would be appropriate for evaluating adrenal function in neonatal foals.