Monitoring Dogs with Cushing’s Disease on Trilostane: ACTH Stimulation vs Pre-Pill Cortisol (and Why Your Dog’s Journal Matters)

TL;DR

Dogs on trilostane (Vetoryl®) must be monitored to avoid both under-control (persistent Cushing’s signs) and over-suppression (Addison-like illness).
Two common approaches: the ACTH stimulation test and a single “pre-pill” (pre-trilostane) cortisol.
Growing evidence shows pre-pill cortisol correlates better with day-to-day control when combined with the owner’s clinical diary, and it avoids the cost/availability issues of cosyntropin used for ACTH testing.
My preferred approach: owner journal + pre-pill cortisol for routine checks; ACTH stimulation when the dog is unwell, after major dose changes, or when results and clinical signs don’t match.

Why monitoring matters

Trilostane reduces cortisol production. If we don’t monitor, dogs can remain symptomatic (PU/PD, panting, hunger, poor coat) or tip into iatrogenic hypoadrenocorticism (vomiting, lethargy, collapse). Routine monitoring helps keep dogs feeling their best and catches problems early. The product label emphasizes regular rechecks at 10–14 days, 30 days, 90 days, and every 3 months after dose changes.

Option 1: ACTH stimulation test

What it tells us
Measures adrenal “reserve” (how much cortisol the glands can make when pushed). Traditionally the standard for monitoring trilostane. Label-based schedules still center on ACTH testing.

Pros

Longstanding reference method; detects over-suppression risk.

Cons

Costly and dependent on cosyntropin supply; requires two blood draws and strict timing.
Several studies show weaker correlation with a dog’s real-world control compared with pre-pill cortisol.

How to perform (practical protocol)

Give trilostane with food, then time the test 4–6 hours after the dose (peak effect window per label).
Draw baseline serum cortisol.
Give cosyntropin 5 µg/kg IV or IM (max 250 µg/dog).
Draw the post-ACTH sample at 60 minutes.
Interpret alongside clinical signs.

Notes for clinicians: Low-dose protocols (e.g., 1 µg/kg IV) can be acceptable for monitoring trilostane but not for diagnosing HAC; follow your lab’s guidance.

Option 2: Pre-pill (pre-trilostane) cortisol

What it tells us
A single cortisol drawn immediately before the next trilostane dose (when the drug’s effect has waned). Multiple studies show better alignment with owner-reported control than ACTH testing.

Pros

One blood draw, easier to schedule, lower cost (no cosyntropin).
Strong correlation with clinical control and owner questionnaires.

Cons

Must be collected consistently (same time relative to dosing/feeding).
Not appropriate if the dog is ill or showing signs of cortisol deficiency—those dogs warrant a full work-up (often including ACTH).

How to perform (practical protocol)

Do not give the next trilostane dose yet.
Collect serum within 0–2 hours before the scheduled dose (≈24 h after last dose if once-daily; ≈12 h if twice-daily).
Feed and dose after the blood draw.
Keep visit-to-visit timing as identical as possible.
Interpret with the history/exam. Common working ranges used by many internists:
- ~1.5–5.0 µg/dL (40–138 nmol/L) → typically adequate control
- >5.0 µg/dL (>138 nmol/L) → often inadequate control (consider dose/diet/timing)
- <1.5 µg/dL (<40 nmol/L) → possible over-suppression (assess for illness; may need ACTH).

My monitoring preference: Owner journal + pre-pill cortisol

A structured owner diary plus a consistent pre-pill cortisol gives a more “real life” picture of control, agrees better with how the dog feels at home, and avoids cosyntropin-related costs/availability issues. Multiple analyses (RVC/VetCompass and others) support the value of pre-trilostane cortisol (alone or paired with a 3-hour post-pill sample) outperforming post-ACTH cortisol for classifying control.

That said, the Vetoryl® label still centers on ACTH testing, and your veterinarian may reasonably choose ACTH at specific milestones or whenever concerns arise. We individualize for each patient.

When to favor an ACTH stimulation test

Your dog seems unwell (vomiting, diarrhea, lethargy, collapse, anorexia).
Electrolyte changes suggest Addison-like effects.
After a major dose change or if pre-pill results and clinical signs don’t match.
When your clinic prefers to follow label-based monitoring.

Owner journal: what to track (daily or at least 3–4×/week)

Water intake (cups/day) & urination (frequency/accidents).
Appetite (normal / ravenous / decreased).
Panting (none / mild / moderate / heavy; time of day).
Energy & activity (walk tolerance, play).
Skin/coat (shedding, dandruff, thin hair, new infections).
Body weight (weekly).
Behavior & sleep (restlessness, pacing, nighttime waking).
This diary is gold during rechecks and lets us make data-driven dose decisions.

Protocols at a glance (for busy clinics)

Pre-pill cortisol (routine check in a well dog)

Schedule draw right before the next dose (match timing every visit).
Pull single serum cortisol.
Feed + give trilostane after sampling.
Interpret with owner diary; target roughly 1.5–5.0 µg/dL.

ACTH stimulation (safety/label milestone or if ill)

Give trilostane with food; test 4–6 h post-dose.
Draw baseline cortisol → cosyntropin 5 µg/kg IV/IM (max 250 µg) → 60-min cortisol.
Assess alongside clinical signs and chemistry/electrolytes.

Frequently asked questions

Is pre-pill cortisol really “better” than ACTH?
For judging clinical control, several studies show stronger correlation between pre-trilostane cortisol (± a 3-hour post-pill) and owner-reported control than with post-ACTH cortisol. It’s not that ACTH is “wrong”—it’s that different questions are being asked: reserve vs real-life control.

Will we ever stop doing ACTH tests?
Unlikely. ACTH remains valuable for safety checks and tricky cases, and it’s still the labeled method in many regions.

Is pre-pill cortisol safe to use alone?
Use it only when the dog is clinically well; if your dog seems off, call your vet, as an ACTH test (and broader work-up) may be the safer path.

References & further reading

Pre-pill ± 3-hr post-pill cortisol outperforming post-ACTH for classifying control; better correlation with owner scores. PMC PubMed
Comparative methods (12 strategies) for monitoring trilostane; supports clinical-sign–aligned approaches. PMC
Practical guidance summarizing evidence (AAHA 2024; VET.CT 2025) on pre-pill cortisol & clinical correlation. AAHA resources.vet-ct.com
Label-based timing & intervals for Vetoryl (ACTH 4–6 h post-dose; milestone rechecks). dechra-us.com
ACTH protocols & dosing (5 µg/kg up to 250 µg; 60-min sample; low-dose note for monitoring). tvmdl.tamu.edu Antech Diagnostics

Bottom line: Pair a thoughtful owner journal with consistent pre-pill cortisol for routine monitoring, and keep ACTH stimulation in your toolkit for safety checks and complex cases. That balance keeps dogs safer, happier, and helps families spend more on wellness and less on testing.