Comparison of 2 Doses for ACTH Stimulation Testing in Dogs Suspected of or Treated for Hyperadrenocorticism

Abstract

BackgroundLowering the cosyntropin dose needed for ACTH stimulation would make the test more economical.ObjectivesTo compare the cortisol response to 1 and 5 μg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism (HAC) and in dogs receiving trilostane or mitotane for pituitary‐dependent HAC.AnimalsHealthy dogs (n = 10); client‐owned dogs suspected of having HAC (n = 39) or being treated for pituitary‐dependent HAC with mitotane (n = 12) or trilostane (n = 15).ProceduresIn this prospective study, healthy dogs had consecutive ACTH stimulation tests to ensure 2 tests could be performed in sequence. For the first test, cosyntropin (1 μg/kg IV) was administered; the second test was initiated 4 hours after the start of the first (5 μg/kg cosyntropin IV). Dogs suspected of having HAC or being treated with mitotane were tested as the healthy dogs. Dogs receiving trilostane treatment were tested on consecutive days at the same time post pill using the low dose on day 1.ResultsIn dogs being treated with mitotane or trilostane, the 2 doses were pharmacodynamically equivalent (90% confidence interval, 85.1–108.2%; P = 0.014). However, in dogs suspected of having HAC, the doses were not pharmacodynamically equivalent (90% confidence interval, 73.2–92.8%; P = 0.37); furthermore, in 23% of the dogs, clinical interpretation of test results was different between the doses.Conclusions and Clinical RelevanceFor dogs suspected of having HAC, 5 μg/kg cosyntropin IV is still recommended for ACTH stimulation testing. For dogs receiving mitotane or trilostane treatment, a dose of 1 μg/kg cosyntropin IV can be used.

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

“…The C D may not apply because the dogs in our study were not treated with mitotane or trilostane and had [cortisol] that exceeded the current recommendation for clinically controlled treated dogs 3. Nevertheless, a counter argument would be that the ultimate goal of treatment with mitotane or trilostane is to use the lowest dose that will cause adrenal suppression and lead to alleviation of clinical signs of HC, similar to the healthy dogs in our study.…”

“…We found that only a C D > 3.3 μg/dL (92 nmol/L) was substantial and not due to biological or analytical variability. For example, a recently used classification3 assumed the following clinical classes for [cortisol]: “excessively treated” <1.1 μg/dL (<30 nmol/L), “ideal control” 1.1–5.4 μg/dL (30–150 nmol/L), “acceptable control” >5.4–9.0 μg/dL (>150–250 nmol/L), and “inadequate control” >9.0 μg/dL (>250 nmol/L). Accordingly, a clinically well‐controlled dog with [cortisol] of 4.3 μg/dL (120 nmol/L) can be classified as being “excessively treated,” or with “ideal” or “acceptable” control if the second visit test result is within 1.0–7.7 μg/dL (28–212 nmol/L) where in reality, this change in [cortisol] could be due to biological and analytical variability.…”

“…The C D may not apply because the dogs in our study were not treated with mitotane or trilostane and had [cortisol] that exceeded the current recommendation for clinically controlled treated dogs. 3 Nevertheless, a counter argument would be that the ultimate goal of Table 1. The results of the mean, %CV between , % CV within , %CV analytic , Var between , Var within , Var analytic , C D , C D %mean, and IoI for serum cortisol post-ACTH stimulation, and the numbers of measurements required to assess the homeostatic set point of serum cortisol post-ACTH with confidence intervals of 90 and 95%.…”

“…Therefore, the clinician sometimes faces difficulty in arriving at a definitive diagnosis of HC. Additionally, monitoring the concentration of serum cortisol concentration ([cortisol]) post‐ACTH stimulation is an established method of assessing response to treatment with mitotane or trilostane, and [cortisol] has been used by some to classify the response to treatment as “excessive,” “ideal,” “acceptable,” or “inadequate.”3 …”

“…Additionally, monitoring the concentration of serum cortisol concentration ([cortisol]) post-ACTH stimulation is an established method of assessing response to treatment with mitotane or trilostane, and [cortisol] has been used by some to classify the response to treatment as "excessive," "ideal," "acceptable," or "inadequate." 3 The total variability of a diagnostic test affects its performance and influences the way the clinician should use the test. The total variability consists of the components of within-and between-individual biological variability, and the component of analytical variability.…”