Background: Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders. Hypotheses: (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). Animals: Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). Methods: Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season-matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. Results: Free cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 μg/dL) compared to lean controls (0.2 ± 0.1 μg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 μg/dL, P = .005) or ID (8.8 ± 10.2 μg/dL, P = .039) than controls (5.0 ± 0.9 μg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 μg/dL; ID: 5.0 ± 4.5 μg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 μg/dL). Conclusions and Clinical Importance: Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses.

Background: Transient hypothalamic-pituitary-adrenal (HPA) axis dysfunction occurs frequently in critically ill humans and impacts survival. The prevalence and impact of HPA axis dysfunction in critically ill neonatal foals are not well characterized. Hypotheses: (1) HPA axis dysfunction occurs in hospitalized neonatal foals, and is characterized by inappropriately low basal serum cortisol concentration or inadequate cortisol response to exogenous adrenocorticotropic hormone (ACTH); (2) hospitalized foals with HPA axis dysfunction have more severe disease and are less likely to survive than hospitalized foals with normal HPA axis function. Animals: Seventy-two hospitalized foals and 23 healthy age-matched foals. Methods: Basal ACTH and cortisol concentrations were measured and a paired low-dose (10 μg)/high-dose (100 μg) cosyntropin stimulation test was performed at admission in hospitalized foals. HPA axis dysfunction was defined as (1) an inappropriately low basal cortisol concentration or (2) an inadequate increase in cortisol concentration (delta cortisol) after administration of cosyntropin, with cut-off values for appropriate basal and delta cortisol concentrations determined from results obtained in healthy age-matched foals. Results: Forty-six percent of hospitalized foals had an inappropriately low basal cortisol concentration and 52% had an inadequate delta cortisol concentration after administration of the 100 μg dose of cosyntropin. An inadequate delta cortisol response to the high (100 μg) dose of cosyntropin was significantly correlated with shock and multiple organ dysfunction syndrome in hospitalized foals, and with decreased survival in a subgroup of septic foals. Conclusions and Clinical Importance: HPA axis dysfunction occurs frequently in hospitalized neonatal foals, and negatively impacts disease severity and survival.

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±8.1 μg/dL; free = 3.5±4.8 μg/dL versus total = 10.8±6.0 μg/dL; free = 6.9±3.3 μg/dL in foals without shock) and in nonsurvivors (total = 3.8±6.9 μg/dL; free = 1.9±3.9 μg/dL versus total = 9.1±7.7 μg/dL; free = 5.5±4.4 μg/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.