Why Trilostane Monitoring Matters
Trilostane (Vetoryl) is the first-line medical treatment for canine Cushing’s disease (hyperadrenocorticism) — a competitive inhibitor of 3-beta-hydroxysteroid dehydrogenase that reduces cortisol synthesis.
Monitoring is critical because trilostane has a narrow therapeutic window:
- Too little → Cushing’s signs persist (PU/PD, polyphagia, alopecia, pot belly, recurrent infections)
- Too much → Iatrogenic Addison’s disease (lethargy, anorexia, vomiting, collapse) — can be fatal if not recognised
The ACVIM consensus target ranges and dose adjustment framework guide safe, effective treatment.
The Standard Monitoring Test – ACTH Stim
Post-ACTH cortisol at 4-6 hours after the morning dose is the conventional monitoring test:
| Post-cortisol (ÎĽg/dL) | Post-cortisol (nmol/L) | Interpretation | Action |
|---|---|---|---|
| <1.0 | <28 | Over-suppressed | STOP trilostane, restart at lower dose |
| 1.0-1.5 | 28-40 | Borderline low | Monitor closely; consider mild reduction |
| 1.5-5.4 | 40-150 | OPTIMAL | Maintain current dose |
| 5.5-9.1 | 150-250 | Acceptable | Maintain if signs controlled; increase if not |
| 9.2-13.6 | 250-375 | Under-control | Increase dose 25-50% |
| >13.6 | >375 | Poor control | Increase dose 50-100% or switch to q12h |
Alternative – Pre-Pill Cortisol Monitoring
Boretti et al. 2017 and Macfarlane et al. 2018 validated pre-pill cortisol as alternative to ACTH stim:
- Cheaper (no cortrosyn needed)
- Avoids cortrosyn shortage (recurring industry issue)
- Sample drawn JUST BEFORE the next dose
Target ranges:
- <1.0 μg/dL → Over-suppressed
- 2-4 μg/dL (55-110 nmol/L) → Ideal
- 4-8 μg/dL (110-220 nmol/L) → Acceptable
- >8 μg/dL (>220 nmol/L) → Under-control
ACTH stim is still considered the gold standard by many specialists, but pre-pill cortisol is acceptable when cortrosyn unavailable or budget constrained.
When To Monitor
| Time | Test |
|---|---|
| 14 days after starting | First ACTH stim — establishes baseline response |
| 30 days | Second check — confirms stability |
| 90 days | Third check — long-term control assessment |
| Every 3-6 months once stable | Routine monitoring |
| 14 days after any dose change | Recheck before further changes |
| Any clinical concern | Anytime if Addison’s signs |
Dose Adjustment Framework
Starting Dose
Typical 2-3 mg/kg/day, given once daily with food.
Common starting doses by weight:
| Weight | Trilostane dose |
|---|---|
| <5 kg | 10 mg q24h |
| 5-10 kg | 30 mg q24h |
| 10-20 kg | 30-60 mg q24h |
| 20-40 kg | 60-120 mg q24h |
| >40 kg | 120-240 mg q24h |
Dose Adjustments
| Current control | Action |
|---|---|
| Optimal (1.5-5.4 ÎĽg/dL post) | Maintain |
| Under-control 9-14 ÎĽg/dL post | Increase 25-50% OR switch to q12h |
| Poor control >14 ÎĽg/dL post | Increase 50-100% OR confirm compliance |
| Over-suppression <1.0 ÎĽg/dL post | STOP for 3-7 days, restart at 25-50% lower dose |
Recheck ACTH stim 14 days after any dose change before further adjustment.
Twice-Daily Dosing
Twice-daily (q12h) dosing is increasingly used:
- More consistent cortisol suppression than q24h
- Often achieves better clinical control in dogs with adrenal disease
- Slightly lower total daily dose sometimes needed
- Better tolerated in some dogs vs single larger morning dose
When to switch to q12h: dogs not controlled on q24h despite adequate dose; dogs with prominent end-of-day PU/PD; specialist preference.
Giving Trilostane Correctly
ALWAYS give with food — absorption increases 3-5× with food vs fasting. This is a major source of treatment failure.
- Consistent timing — same time each day
- Whole capsule if possible — compounding pharmacies can split for small dogs
- Food — small treat or full meal both work
Addison’s Crisis Warning
The major adverse event of trilostane is iatrogenic Addison’s disease:
Warning signs:
- Lethargy
- Anorexia
- Vomiting / diarrhoea
- Weakness / collapse
- Bradycardia
If signs develop: STOP TRILOSTANE and seek vet attention same day.
Differentiating isolated glucocorticoid suppression from full Addisonian crisis:
- Electrolytes Na/K ratio:
- Normal Na, normal K (>23) → isolated glucocorticoid suppression; reverses with trilostane withdrawal
- Low Na, high K (Na/K <23) → full Addison’s; requires emergency treatment
Most trilostane-induced suppression is isolated cortisol and reverses within days of withdrawal.
Emergency treatment if collapsed:
- IV fluids (saline)
- Dexamethasone 0.1-0.2 mg/kg IV (does NOT cross-react with ACTH stim)
- Sometimes mineralocorticoid replacement if true Addison’s
- Hospitalisation for 24-72 hours
What To Monitor Beyond Cortisol
Annual checks for dogs on trilostane:
- Full senior bloodwork — CBC, biochemistry, electrolytes
- Urinalysis with UPC — proteinuria is common in Cushing’s even with treatment
- Blood pressure — hypertension common; treat with amlodipine/telmisartan
- Body condition score — track weight, muscle, coat
- Clinical signs review — PU/PD, polyphagia, alopecia, pot belly, exercise tolerance
Common Pitfalls
Poor Control Despite Adequate Dose
Investigate:
- Compliance — is the owner giving with food consistently?
- Timing of ACTH stim — must be 4-6 hours post-pill
- Drug source / quality — generic trilostane absorption may vary
- Concurrent disease — diabetes, hypothyroidism, infection
- Diagnosis — reconsider if no response despite high doses
Over-Suppression in Stable Dog
Triggers:
- Inappetence — reduced food intake increases trilostane effect
- Concurrent illness — sick dog more sensitive
- Drug interaction — ketoconazole, fluconazole increase trilostane levels
Clinical Signs Persist Despite Biochemical Control
Investigate:
- Concurrent disease — diabetes mellitus, hypothyroidism, neoplasia, UTI
- Pituitary macroadenoma — neurological signs (circling, behaviour change, blindness)
- Time — coat regrowth and muscle recovery take 3-6 months
Adrenal-Dependent Disease
About 15-20% of Cushing’s cases are adrenal-dependent (adrenal tumour) rather than pituitary-dependent.
Workup if poor trilostane response:
- Abdominal ultrasound — adrenal mass identification
- Abdominal CT — better characterisation, surgical planning
- High-dose dexamethasone suppression test (HDDS) — differentiates pituitary vs adrenal
- Endogenous ACTH — low in adrenal disease
Adrenal tumour treatment options:
- Adrenalectomy — curative if benign; specialist surgery
- Trilostane — controls cortisol production in many
- Mitotane — selective adrenocortical necrosis (older approach)
When To Refer
Internal medicine or endocrinology referral appropriate for:
- Adrenal-dependent disease (adrenal mass on imaging)
- Pituitary macroadenoma (neurological signs)
- Persistent poor control despite multiple dose increases
- Repeated over-suppression events
- Concurrent diabetes mellitus (insulin requirements change with cortisol)
Honest Caveats
- Trilostane is a daily lifelong commitment in most dogs — diligent monitoring needed
- Cost of trilostane + monitoring is significant — typical $100-300/month including drug + bloods
- Some dogs don’t respond despite optimal management — adrenal-dependent disease, drug-resistant, comorbidities
- Quality of life over numerical perfection — many dogs do well at the upper end of “acceptable” range with no signs
- Treatment is suppressive, not curative — without lifetime treatment, signs return
Conclusion
Trilostane monitoring is the cornerstone of safe and effective Cushing’s treatment. Post-ACTH stim cortisol 1.5-5.4 ÎĽg/dL is the ACVIM consensus optimal range. Pre-pill cortisol is a validated alternative (especially during cortrosyn shortage). Always give trilostane with food for adequate absorption. Recheck 14 days after dose changes, then every 3-6 months once stable. Watch for Addisonian crisis signs — lethargy, anorexia, vomiting — and STOP trilostane if they develop. Quality of life and clinical sign resolution matter more than tight numerical control. With careful monitoring, most dogs respond well to trilostane with 2-3 year median survival post-diagnosis and substantially improved quality of life.
Frequently Asked Questions
What is the target cortisol on trilostane?
Per ACVIM consensus, POST-ACTH STIM CORTISOL target is 1.5-5.4 ug/dL (40-150 nmol/L) for OPTIMAL control; 5.5-9.1 ug/dL (150-250 nmol/L) acceptable; over 9.1 indicates under-control; under 1.5 indicates over-suppression risk. Pre-pill cortisol alternative (Boretti 2017 / Macfarlane 2018): ideal 2-4 ug/dL (55-110 nmol/L), acceptable 4-8 ug/dL, over 8 inadequate, under 1 over-suppressed. ACTH stim sample drawn 4-6 hours post-morning dose; pre-pill drawn just before next dose.
How often should ACTH stim be done on trilostane?
Standard protocol: 14 DAYS after starting; 30 DAYS; 90 DAYS; then EVERY 3-6 MONTHS once stable. After ANY DOSE CHANGE, recheck in 14 days before further adjustments. Annual senior bloodwork + urinalysis with UPC + blood pressure regardless. Recheck SAME DAY if Addisonian signs (lethargy, anorexia, vomiting, collapse) develop. Some specialists do less frequent (annual) ACTH stim in stable dogs many years on treatment with consistent clinical control.
Why give trilostane with food?
Trilostane absorption increases 3-5x with food vs fasting. This is a critical pharmacokinetic feature – giving with food (small treat or full meal both work) substantially increases drug effect. Inconsistent feeding times relative to dosing is one of the major causes of poor control despite adequate prescribed dose. Owners should establish a CONSISTENT routine – same food, same time, same way each day. If a dose is missed, give as soon as remembered with food; if more than 6 hours late, skip and resume next day.
What does over-suppression on trilostane mean?
Over-suppression = post-ACTH stim cortisol below 1.0 ug/dL (or pre-pill cortisol below 1.0). Indicates excessive adrenal suppression. Risk of iatrogenic ADDISON’S DISEASE – lethargy, anorexia, vomiting, diarrhoea, weakness, collapse. Most over-suppression is ISOLATED GLUCOCORTICOID (Na/K normal) and reverses within days of trilostane withdrawal. Less common but more serious is FULL ADDISON’S (low Na, high K, ratio under 23) requiring IV fluids + glucocorticoid + sometimes mineralocorticoid replacement. STOP trilostane immediately, restart at LOWER dose (25-50% reduction) after 3-7 days. Recheck ACTH stim in 14 days at new dose.
Should I switch from once-daily to twice-daily trilostane?
Twice-daily (q12h) dosing is INCREASINGLY USED and often achieves BETTER CONTROL than once-daily in dogs with adrenal disease. Reasons to switch: dog NOT controlled on q24h despite adequate dose; PROMINENT END-OF-DAY signs (PU/PD worsens late afternoon/evening); SPECIALIST PREFERENCE. The total daily dose may be similar or slightly LOWER on q12h dosing due to more consistent cortisol suppression. Discussion with your vet/endocrinologist appropriate – both protocols have evidence support, and individual dog response varies.
What is the survival on trilostane for dogs with Cushing’s?
Median survival on trilostane treatment is approximately 2-3 YEARS post-diagnosis. Most dogs are SENIOR at diagnosis (typically 8-12 years old) so COMORBIDITIES OFTEN DETERMINE SURVIVAL rather than Cushing’s directly. About 75% of dogs achieve good biochemical AND clinical control on trilostane. Quality of life substantially improves with treatment – PU/PD resolves within 2-4 weeks, polyphagia next, coat regrowth 3-6 months. Annual mortality includes about 10% adverse drug events (most reversible). Pituitary macroadenoma development (neurological signs) over time affects some pituitary-dependent cases; adrenal-dependent dogs may benefit from adrenalectomy.
Related PuppaDogs Calculators
Continue building your dog’s personalised care plan with these related PuppaDogs calculators:
- Dog Pregnancy / Whelping Due-Date Calculator
- Puppy Weight Predictor (Adult Weight Calculator)
- Heatstroke Risk Calculator for Dogs
- Bloat (GDV) Risk Calculator for Dogs
- Dog Life Expectancy Calculator (Breed, Body Condition, Lifestyle)
- Spay/Neuter Timing Calculator for Dogs (Breed-Specific)
References & Further Reading
The dosing ranges and safety information on this page are drawn from the following veterinary references. Always defer to your own veterinarian and the manufacturer’s label for your specific product.
- Behrend EN, Kooistra HS, Nelson R, et al. ACVIM consensus statement: diagnosis of spontaneous canine hyperadrenocorticism. JVIM, 2013.
- Boretti FS, Holzthuem J, Reusch CE, Sieber-Ruckstuhl NS. Evaluation of baseline cortisol, endogenous ACTH and cortisol/ACTH ratio to monitor trilostane treatment in dogs with pituitary-dependent hypercortisolism. JVIM, 2017.
- Macfarlane L, Parkin T, Ramsey I. Pre-trilostane and three-hour post-trilostane cortisol to monitor trilostane therapy in dogs. Veterinary Record, 2016.
- Vetoryl (trilostane) prescribing information – Dechra Veterinary Products.
- Ramsey IK. Trilostane in dogs. Veterinary Clinics of North America: Small Animal Practice.
- Plumb’s Veterinary Drug Handbook – trilostane monograph.
- PuppaDogs. Cushing’s Pre-Test Probability Calculator and Vetoryl Dosage Calculator. puppadogs.com.
