Evaluation of clinical, ultrasonographic, and clinicopathological findings in dogs with pituitary-dependent hypercortisolism and poor trilostane response

BACKGROUND: Trilostane is the treatment of choice for pituitary-dependent hypercortisolism (PDH) in dogs, but predictors of a poor response are unclear. HYPOTHESIS/OBJECTIVES: To identify variables associated with a poor response to trilostane in dogs with PDH. ANIMALS: Twenty-three dogs with PDH treated with trilostane. METHODS: Retrospective cohort study. Clinical, clinicopathological, endocrine, ultrasonographic, and treatment data were reviewed. Dogs were classified as good responders (GRs) or nonresponders (NRs) based on clinical outcomes after 4-8 months of trilostane treatment. The primary outcome was treatment response. RESULTS: Fifteen dogs were GRs and 8 were NRs. At diagnosis, GRs had lower alanine aminotransferase (ALT) (median [IQR] 182 [70-251] vs 330 [224-578] U/L; P = .004), eACTH (14.4 [9.25-29.13] vs 49.2 [34.35-62.35] pg/mL; P = .007), and pre-ACTH cortisol (4.28 [3.07-6.52] vs 9.0 [6.57-19.40] μg/dL; P = .019) than NRs. Bilateral adrenomegaly was more frequent in NRs (8/8) than in GRs (9/15; P = .007). At T1, NRs required more rechecks (median [IQR] 7 [6-7] vs 3 [3-5]; P < .001) and higher trilostane doses (3.25 [3-5.75] vs 1.22 [0.66-1.60] mg/kg q12h; P < .001). After false discovery rate adjustment, ALT, eACTH, alopecia, and bilateral adrenomegaly remained significant (q = 0.047 for each). All GRs achieved complete clinical resolution within 4 months of treatment initiation. CONCLUSIONS AND CLINICAL IMPORTANCE: Higher baseline ALT, eACTH, and pre-ACTH cortisol, as well as bilateral adrenomegaly, were associated with a poor response to trilostane. A lack of improvement by 4-8 months and the need for higher doses or more rechecks supports early therapeutic reassessment.