A prospective observational study evaluated the efficacy and safety of low-dose q12h trilostane with high-dose q24h trilostane when treating dogs with pituitary-dependent hyperadrenocorticism (PDH). The low-dose group (n = 9) received 0.78 ± 0.26 mg of trilostane/kg body weight q24h; the high-dose group (n = 7) received 30 mg of trilostane/dog q24h. Improvement in ACTH-stimulated serum cortisol concentrations and clinical signs occurred slower in the low-dose group than in the high-dose group. Improvement was noted at 24 weeks for all dogs. None of the dogs in the low-dose group developed concerning adverse effects; however, signs and abnormal laboratory findings consistent with transient hypoadrenocorticism were observed in 2 dogs in the high-dose group after 20 weeks of treatment, evidence that the occurrence of adverse effects in dogs treated with trilostane is dose related. Adrenal necrosis and associated inflammation have been described in postmortem examinations of dogs treated with trilostane; it has been suggested that severity of these findings is related to dose and duration of treatment and that dogs treated with trilostane for >1 year were more likely to exhibit prolonged hypoadrenocorticism. In dogs with PDH, low-dose trilostane q12h is effective with potentially fewer adverse effects.

Commentary
Trilostane is effective in treating PDH, but the initial daily dose recommended by the manufacturer has been considered higher than necessary. This study revealed that low-dose and high-dose protocols were similarly efficacious over time. Two dogs in the high-dose group developed signs and abnormal laboratory findings consistent with hypoadrenocorticism, which is a significant concern when using trilostane. The high-dose group achieved more rapid results but presented more risk for development of hypoadrenocorticism. The low-dose protocol took longer to obtain desired results and required q12h administration, but, more importantly, is a safer and equally effective protocol.—Dara Zerrenner, VMD, MS, DACVIM

Source
Efficacy of low- and high-dose trilostane treatment in dogs (<5 kg) with pituitary-dependent hyperadrenocorticism. Cho KD, Kang JH, Chang D, et al. JVIM 27:91-98, 2013.