Study of the effects of once daily doses of trilostane on cortisol concentrations and responsiveness to adrenocorticotrophic hormone in hyperadrenocorticoid dogs

Abstract

The effects of trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor on basal cortisol concentrations and the results of ACTH stimulation tests in dogs with pituitary-dependent hyperadrenocorticism were investigated. In eight of nine dogs trilostane suppressed the concentration of cortisol below the lower limit of the reference range (<50 nmol/l) for a mean (sd) of 3.5 (2.3) hours during the day, but for no longer than 13 hours. In another 10 dogs, there was a clear difference between the post ACTH cortisol concentrations observed four and 24 hours after the administration of trilostane. Furthermore, in the six dogs whose clinical signs were poorly controlled the post-ACTH concentrations observed four and 24 hours after the administration of trilostane were always higher than the equivalent cortisol concentrations in the four dogs whose clinical signs were controlled. A short duration of drug action may be responsible for the failure of some dogs to respond adequately to once daily trilostane administration.

Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

“…Results of this study suggest that in the population examined, serum cortisol concentrations measured before and after ACTH stimulation 9–12 hours after trilostane administration are significantly higher than those measured at 3–6 hours after trilostane administration. Although several other studies have documented that serum cortisol concentrations measured before and after ACTH stimulation are lower shortly after trilostane administration compared to several hours later, these studies examined a heterogeneous population of trilostane‐treated dogs with hyperadrenocorticism 2, 4, 7, 8. The present study is unique because it was performed in a particular subset of trilostane‐treated dogs with well‐regulated hyperadrenocorticism and low cortisol concentrations shortly after trilostane administration.…”

Trilostane in Dogs

“…However it has been demonstrated that the effect of trilostane on basal and ACTH stimulated cortisol is considerably less than 24 hours in most cases [24]. In the same study the authors also documented six dogs with HAC whose clinical signs were poorly controlled and whose post-ACTH concentrations observed four and 24 hours after the administration of trilostane were always higher than the equivalent cortisol concentrations in four dogs whose clinical signs were controlled.…”

“…However due to the relatively short lasting effects of trilostane the ACTH stimulation test varies considerably with the time of testing relative to dosing [24]. Early studies of trilostane were often conducted without the knowledge of later studies and so the clinical effects were sometimes discordant to the ACTH stimulation test results.…”

“…The short duration of action of trilostane may have a protective effect against the development of hypoadrenocorticism, as many dogs with no serum cortisol response to ACTH stimulation 2 -3 hours post trilostane dosing, do not develop signs of hypoadrenocorticism [19]. However equally many dogs that have a target level post ACTH stimulation test serum cortisol will exhibit signs of HAC [20,24]. Various different timings and cortisol target levels for the ACTH stimulation test when used to monitor trilostane therapy have been used [18][19][20][21][22][23].…”

Comparison of Adrenocorticotropic Hormone Stimulation Test Results Started 2 versus 4 Hours after Trilostane Administration in Dogs with Naturally Occurring Hyperadrenocorticism

“…Trilostane treatment, at appropriate doses and frequency of administration, may control many of the clinical and biochemical abnormalities associated with canine NOH 3, 4, 5, 6, 7. However, there is uncertainty in the literature regarding what test might serve as an objective, specific, and sensitive means of assessing therapeutic response to trilostane 6, 7, 8.…”