Biological Variability in Serum Cortisol Concentration Post-adrenocorticotropic Hormone Stimulation in Healthy Dogs

Background: The ACTH stimulation has low sensitivity for the diagnosis of hypercortisolism possibly as a result of biological and analytical variability. Hypothesis/Objectives: To report the components of biological and analytical variability in serum cortisol concentration post-ACTH stimulation ([cortisol]) in healthy dogs. Animals: Fourteen healthy harrier hound dogs. Methods: The data were extracted from a separate, prospective, randomized, double-blinded, controlled discovery study in which dogs treated with vehicle control and 4 different doses of cortisone acetate (CA) for 7 days had an ACTH stimulation test performed to confirm the dose-dependent effect of CA. The index of individuality (IoI), the critical difference between sequential measurements (C_D), and the number of measurements required to assess the homeostatic set point (HSP) of [cortisol] with confidence intervals (CI) of 90 and 95% were estimated. Results: The IoI was equal to 1.1 and the C_D was 3.3 μg/dL (92 nmol/L). The number of measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were 3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in females (13.3 ± 4 μg/dL [366 ± 114 nmol/L] vs. 11.5 ± 2.5 μg/dL [318 ± 65 nmol/L], respectively; P =.046). As expected, treatment with CA resulted in a dose-dependent suppression of [cortisol]. Conclusions and Clinical Importance: False-negative test results in hypercortisolism could occur when [cortisol] is outside of the individual's HSP and within the reference interval. The large C_D emphasizes the importance of assessing clinically relevant parameters in the diagnosis and monitoring of HC.