Trilostane (Vetoryl) for Canine Hyperadrenocorticism: Evidence and Monitoring

Bottom line

• Trilostane (Vetoryl) is a competitive inhibitor of 3-beta-hydroxysteroid dehydrogenase, licensed for pituitary-dependent and adrenal-dependent hyperadrenocorticism (HAC) in dogs. [2]
• In a prospective cohort of 78 dogs treated for up to three years, polyuria/polydipsia completely resolved in 70% and skin changes in 62%; post-ACTH cortisol fell below 250 nmol/L in 81% within one month of starting treatment. [1]
• Iatrogenic hypoadrenocorticism is the key safety risk, but it was uncommon: only 2 of 78 dogs in the Neiger 2002 cohort developed biochemical hypoadrenocorticism. Adrenal-function monitoring remains obligatory throughout therapy. [1]
• As of July 2026, the best available monitoring evidence indicates pre-trilostane and 3-hour post-trilostane cortisol correlate better with clinical control than the traditional post-ACTH stimulation test, with a pre-trilostane cortisol of ≤138 nmol/L giving 86.5% specificity for excellent control. [2]

Drug facts

• Class: Adrenocortical suppressant; 3-beta-hydroxysteroid dehydrogenase (3β-HSD) inhibitor.
• Mechanism: Competitive, reversible inhibition of 3β-HSD blocks synthesis of glucocorticoids and, to a lesser extent, mineralocorticoids from their precursors. [2]
• 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/precautions: Manufacturer recommends against concurrent 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.

How effective is trilostane for canine HAC?

The largest early prospective cohort — Neiger and colleagues, 78 dogs with pituitary-dependent HAC followed for up to three years at the Royal Veterinary College — established trilostane's efficacy and tolerability profile. Clinically meaningful response was common: polyuria and polydipsia completely resolved in 70% of affected dogs and skin changes resolved in 62%. Biochemical response was rapid, with mean basal and post-ACTH cortisol concentrations falling significantly (p<0.001) after a mean of 12.3 days of treatment. The post-ACTH cortisol decreased to less than 250 nmol/L in 81% of dogs within one month of starting treatment, and in a further 15% at a later time point.

Survival data from the same cohort: 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 cortisol vs the ACTH stimulation test

This is the most actively debated question in day-to-day trilostane management, and the evidence favours reassessing the traditional approach.

The conventional method and its unresolved target. The manufacturer recommends monitoring with an ACTH stimulation test started four to six hours post-dosing. This pharmacokinetic timing matters because trilostane's inhibition is competitive and relatively short-acting, so the post-ACTH result is sensitive to the interval since the last dose. [2] However, this ACTH-based approach has never been validated against clinical outcomes, and there is long-standing lack of consensus on the target concentration — published post-ACTH target values range from 15 to 250 nmol/L across different studies. [2]

The evidence for trough (pre-trilostane) and 3-hour cortisol. Macfarlane and colleagues prospectively studied trilostane-treated dogs (67 dogs; 110 monitoring tests) and compared three cortisol-measurement strategies against an owner-completed clinical questionnaire scored by independent veterinarians. Pre-trilostane cortisol and 3-hour post-trilostane cortisol correlated better 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). On ROC analysis both alternatives were superior at 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 identified excellent control with 86.5% specificity, and a 3-hour post-trilostane cortisol of ≤62 nmol/L gave 81.1% specificity for the same distinction. [2]

Practical thresholds and a candidate target range. The pre-trilostane sample is collected at least 12 hours after the last dose. In this cohort the pre-trilostane cortisol was slightly superior to the 3-hour post-trilostane sample and carried the added advantage of flagging oversuppression: dogs with a pre-trilostane cortisol below 40 nmol/L were identified as potentially at risk of iatrogenic hypocortisolism. On this basis the authors proposed a candidate pre-trilostane target range of greater than 40 and less than 138 nmol/L — while explicitly cautioning that these cut-offs need further validation and may not extrapolate directly across different cortisol assay platforms. [2]

Synthesis. The alternatives are logistically simpler and cheaper: a single trough sample at the appropriate interval avoids the time and cost of ACTH stimulation in dogs that are clinically well with stable owner scores, and it doubles as an oversuppression screen. Notably, no unwell dogs in the Macfarlane cohort had biochemical evidence of iatrogenic hypoadrenocorticism, suggesting well and unwell dogs can often be distinguished by questionnaire-identified signs before cortisol results return. [2] The ACTH stimulation test still has a defined role — it remains appropriate when the pre-trilostane cortisol falls outside the candidate range, when it is below 40 nmol/L, or when clinical signs are ambiguous or hypoadrenocorticism is suspected. All of these choices should be integrated with clinical assessment, the product datasheet, and individual patient history.

Safety and adverse effects

The dominant clinical risk is iatrogenic hypoadrenocorticism, which was uncommon in controlled follow-up — 2 of 78 dogs in the Neiger cohort developed clinical and biochemical signs. [1] Adrenal necrosis is a less common but recognised adverse event, particularly at higher doses. Label common adverse effects include lethargy, decreased appetite, vomiting, diarrhoea, and weakness. Because oversuppression can precede overt clinical signs, the pre-trilostane trough cortisol (with the <40 nmol/L flag noted above) is a useful adjunct to routine questionnaire-based assessment. [2]

Contraindications, precautions & PK

• Contraindications/precautions: Manufacturer advises against concurrent drugs that suppress adrenal function; all patients require monitoring for iatrogenic hypoadrenocorticism.
• Pharmacokinetics: Trilostane reversibly and competitively inhibits 3β-HSD, the enzyme required to synthesise cortisol and aldosterone from their precursors. Because the effect is competitive and relatively short-acting, cortisol suppression varies with time since the last dose — the basis for the label's 4–6-hour post-dose ACTH-stimulation timing and for the ≥12-hour interval used when collecting a pre-trilostane trough sample. [2]
• Dosing schedules: 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 on twice-daily regimens), though the optimal monitoring approach for twice-daily dosing is less well-established. Individual dose titration is routine given the wide inter-patient variability in response. [2]

Practical decision support

• First-line management: Trilostane is established as first-line medical therapy for canine HAC, with clinical response in the majority of dogs and a tolerable safety profile. [1]
• Choosing a monitoring test: In a clinically well dog with stable owner-assessment scores, a single pre-trilostane cortisol (≥12 h post-dose) is a reasonable, cheaper first-line monitor. Interpret ≤138 nmol/L as consistent with excellent control and <40 nmol/L as a signal of possible oversuppression. [2]
• When to escalate to ACTH stimulation: Reserve ACTH stimulation for dogs whose pre-trilostane cortisol is outside the candidate range, whose clinical picture is ambiguous, or in whom iatrogenic hypoadrenocorticism is suspected. [2]
• Assay awareness: Proposed cut-offs are assay-dependent and not yet broadly validated; confirm reference behaviour for your laboratory's cortisol platform before adopting fixed thresholds. [2]
• Governance: Always confirm dosing protocols with current formularies and consult the treating internist before modifying monitoring intervals.

Frequently Asked Questions

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Changelog

• 2026-06-07: First published (hub).
• 2026-07-06: Consolidated the 2026-06-14 dispatch on pre-trilostane vs post-ACTH monitoring into this evergreen hub. Corrected the dispatch's citation metadata during the merge — the monitoring study is Macfarlane L, Parkin T, Ramsey I. Vet Rec 2016;179(23):597 (the dispatch's "Norman EJ et al. 2017" attribution was inaccurate for PMC5256409), and the cohort study is Neiger R et al. Vet Rec 2002;150(26):799-804 (not J Vet Intern Med). Added the pre-trilostane <40 nmol/L oversuppression flag, the proposed >40–<138 nmol/L target range, the ≥12-hour trough sampling interval, and the 15–250 nmol/L post-ACTH target-value controversy.