Trilostane (Vetoryl) for Canine Hyperadrenocorticism: Evidence and Monitoring

Bottom line

• Trilostane (Vetoryl) is a competitive inhibitor of 3-beta-hydroxysteroid dehydrogenase, licensed for treating pituitary-dependent and adrenal-dependent hyperadrenocorticism (HAC) in dogs. [2]
• In a cohort of 78 dogs treated for up to three years, polyuria and polydipsia completely resolved in 70% and skin changes resolved in 62%; the post-ACTH cortisol fell below 250 nmol/L in 81% within one month of starting treatment. [1]
• Clinically, iatrogenic hypoadrenocorticism is a key risk; only two of 78 dogs in the Neiger 2002 cohort developed biochemical evidence of hypoadrenocorticism, but adrenal function monitoring is essential throughout treatment. [1]
• Monitoring with pre-trilostane and 3-hour post-trilostane cortisol concentrations may better reflect clinical control than the traditional ACTH stimulation test, according to a prospective clinical study. [2]

Drug facts

• Class: Adrenocortical suppressant; 3-beta-hydroxysteroid dehydrogenase inhibitor
• Mechanism: Competitive inhibition of 3-beta-hydroxysteroid dehydrogenase blocks synthesis of glucocorticoids and, to a lesser extent, mineralocorticoids
• Route/interval: Oral; once or twice daily depending on individual response
• Indication: Pituitary-dependent and adrenal-dependent hyperadrenocorticism in dogs
• Approval: Licensed in many countries as Vetoryl (Dechra)
• Label contraindications: Manufacturer recommends against use with drugs that suppress adrenal function; patients must be monitored for iatrogenic hypoadrenocorticism
• Label common AEs: Lethargy, decreased appetite, vomiting, diarrhoea, weakness; iatrogenic hypoadrenocorticism; adrenal necrosis at high doses

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What the evidence shows

Cohort study: outcomes in 78 dogs treated for up to 3 years (Neiger et al. 2002)

Neiger and colleagues published the largest prospective cohort of trilostane-treated dogs at the time, following 78 dogs with pituitary-dependent HAC for up to three years at the Royal Veterinary College. The drug was well tolerated by almost all dogs; only two of 78 developed clinical signs and biochemical evidence of hypoadrenocorticism.

Clinically meaningful response was common: polyuria and polydipsia completely resolved in 70% of affected dogs and skin changes resolved in 62%. Biochemical response was similarly rapid: mean basal and post-ACTH cortisol concentrations fell significantly (p<0.001) after a mean of 12.3 days of treatment. The post-ACTH stimulation cortisol concentration decreased to less than 250 nmol/L in 81% of dogs within one month of starting treatment, and in an additional 15% at a later time point.

Of 26 dogs that died during the study, the median survival time was 549 days; 51 of the 78 dogs were alive at study completion. [1]

Monitoring: pre-trilostane vs ACTH stimulation test (Macfarlane et al. 2016)

The manufacturer recommends monitoring with ACTH stimulation test started four to six hours post-dosing. However, this approach has never been validated against clinical outcomes. Macfarlane and colleagues prospectively enrolled 67 trilostane-treated dogs and compared three cortisol measurement strategies against an owner-completed clinical questionnaire scored by independent veterinarians.

The study found that pre-trilostane cortisol and 3-hour post-trilostane cortisol were better correlated with the owner clinical score (r=0.38 and r=0.32 respectively, both p<0.001) than post-ACTH stimulation cortisol (r=0.27, p=0.01). Both alternative methods also had superior sensitivity and specificity characteristics on ROC analysis for distinguishing well-controlled from undercontrolled dogs: AUC 0.73 for both pre-trilostane and 3-hour post-trilostane vs 0.64 for post-ACTH cortisol.

A pre-trilostane cortisol of 138 nmol/L or less identified excellent control from undercontrolled cases with 86.5% specificity. A 3-hour post-trilostane cortisol of 62 nmol/L or less gave 81.1% specificity for the same distinction.

Importantly, no unwell dogs had biochemical evidence of iatrogenic hypoadrenocorticism in this study, suggesting that well and unwell dogs can be distinguished by questionnaire-identified signs even before cortisol results are available. [2]

Mechanism and pharmacokinetics

Trilostane reversibly inhibits 3-beta-hydroxysteroid dehydrogenase, an enzyme essential for cortisol and aldosterone synthesis from their respective precursors. Because the inhibition is competitive and relatively short-acting, the ACTH stimulation test result is sensitive to the time elapsed since the last trilostane dose — a key variable in monitoring interpretation. This pharmacokinetic property underlies the recommendation to start the ACTH stimulation test 4-6 hours post-dosing. [2]

Clinical considerations

Twice-daily dosing is used in some dogs to distribute cortisol suppression more evenly across the day; 16 of 110 tests in the Macfarlane cohort were performed on twice-daily regimens. The appropriate monitoring approach for twice-daily dosing is less well-established. Individual dose titration is routine: the Macfarlane cohort showed a median total daily dose across patients that reflected the wide individual variability in response. [2]

How this fits clinical practice

Trilostane is established as first-line medical management for canine HAC, with evidence of clinical response in the majority of dogs and a tolerable safety profile. The key clinical risks are iatrogenic hypoadrenocorticism and — less commonly — adrenal necrosis. Regular biochemical monitoring is obligatory; the emerging evidence suggests pre-trilostane and 3-hour post-trilostane cortisol concentrations may offer practical and clinically informative alternatives to the traditional ACTH stimulation test when tetracosactide is unavailable or expensive. Always confirm dosing protocols with current formularies and consult the treating internist before modifying monitoring intervals.

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References

1. Neiger R, Ramsey I, O'Connor J, Hurley KJ, Mooney CT. Trilostane treatment of 78 dogs with pituitary-dependent hyperadrenocorticism. Vet Rec. 2002;150(26):799-804. https://pubmed.ncbi.nlm.nih.gov/12120922/
2. Macfarlane L, Parkin T, Ramsey I. Pre-trilostane and three-hour post-trilostane cortisol to monitor trilostane therapy in dogs. Vet Rec. 2016;179(23):597. https://pmc.ncbi.nlm.nih.gov/articles/PMC5256409/

Changelog

• 2026-06-07: First published.