Why Trilostane Has to Be Monitored So Carefully
Trilostane (sold as Vetoryl) is the most widely used medication for canine Cushing’s disease, and it is effective — but it is not a “set it and forget it” drug. It works by actively suppressing cortisol production, which means the dose has to be tuned to each individual dog. Too little and the Cushing’s signs persist; too much and cortisol can drop dangerously low. That balance is why monitoring, not just dosing, is the heart of good trilostane care.
Understanding what your vet is checking, and why, makes you a far more effective partner in your dog’s treatment. Here is how monitoring actually works.
How Trilostane Works
Trilostane is a competitive inhibitor (meaning it binds the same chemicals as the enzyme 3-beta-hydroxysteroid dehydrogenase, but with a different effect), which the adrenal glands need in order to make cortisol. Without that enzyme, the main pathway for cortisol formation is blocked. By blocking that step, trilostane lowers cortisol production for a number of hours after each dose. Because the effect is temporary and dose-dependent, the timing of any monitoring test relative to the pill matters enormously.
The ACTH Stimulation Test: The Traditional Standard
For years the ACTH stimulation test has been the standard monitoring tool. The vet draws a baseline blood sample, injects synthetic ACTH to “challenge” the adrenal glands, then measures cortisol again to see how much the glands can produce while the dog is on trilostane. The goal is a post-stimulation cortisol that sits in a controlled range — low enough to relieve signs, but not so low that the dog is under-producing cortisol.
The ACTH stim test is well established, but it has real drawbacks, including: it is relatively expensive, it requires extra clinical time to administer the synthetic ACTH and make two blood draws across several hours, it requires a specific injectable drug that has had supply issues, and — importantly — studies have found that its results do not always line up with how the dog is actually doing at home.
The Shift Toward Pre-Pill Cortisol
Because of those limitations, many specialists have moved toward a simpler measurement: the pre-pill cortisol. Here a single blood sample is drawn just before the next trilostane dose is due (the ideal window is roughly within two hours of the normal dosing time). Research, including work summarized around the ACVIM consensus guidance, suggests that a pre-pill cortisol can distinguish level of disease control at least as well as the ACTH stimulation test — and it correlates well with owner questionnaires about how the dog is doing.
The practical appeal is obvious: one sample instead of two, no expensive stimulating agent, and a result that tracks real-world clinical control. Not every practice has adopted it, and the ACTH Stim test still has a role, but the direction of travel in the literature is clear. In fact, for dogs that are unwell or are uncontrolled and not showing improvement, ACTH stimulation test is still recommended, either in conjunction with a pre-pill cortisol test or as a stand-alone test. (We note that the principal study supporting pre-pill cortisol testing in lieu of ACTH stimulation testing (Macfarlane L, et al.) excluded unwell dogs. So, no conclusions can be drawn from that study with respect to such dogs.) But, for the vast majority of cases, pre-pill cortisol testing seems to be superior, and the trend in the literature clearly favors it.
The Monitoring Schedule
Whichever test your vet uses, the rhythm of monitoring is fairly consistent. Rechecks are typically recommended at about 10 to 14 days and again around 30 days after starting trilostane or after any dose change, because that is when problems tend to surface. Once your dog is well controlled, monitoring usually settles into roughly every three months for the rest of the dog’s life. Bloodwork to check electrolytes and general health is often run alongside the cortisol testing.
If your vet is using the pre-pill cortisol test, the Macfarlane study (and/or the studies cited therein) suggests the following as important thresholds for interpreting the results:
| Less than 1.5 mcg/dL (40 nmol/L) | Indicates that the trilostane dose may be too high (iatrogenic Addison’s disease/hypoadrenocorticism). Your veterinarian may reduce the dosage or, even, increase the dosage based on a combination of Cushing’s signs and further testing. |
| Greater than 1.5 mcg/dL, but less than 5 mcg/dL (138 nmol/L) | Trilostane dosage is controlling Cushing’s. Based on clinical signs, your vet may further increase the dosage or may continue at the current dosage. |
| Greater than 5 mcg/dL, but less than 9 mcg/dL (250 nmol/L) | Trilostane dosage may be increased if clinical signs of Cushing’s persist. |
| Greater than 9 mcg/dL. | Cushing’s is not controlled, and you are almost certainly seeing clinical signs of Cushing’s. Trilostane dosage likely should be increased. |
Long-term use of trilostane can lead to a buildup of intermediate adrenal hormones that, themselves, can cause Cushing’s syndrome, even if cortisol itself is controlled. Thus, periodically, your veterinarian should also check levels of androstenedione, 17-hydroxyprogesterone, estradiol, and progesterone. See the cited Oliver article for more information about this.
What You Can Do at Home
Some of the most valuable monitoring data does not come from the lab — it comes from you. Keeping a simple journal of your dog’s water intake and urination, appetite, energy, panting, and coat gives your vet a real-world picture that blood tests alone cannot provide. If your dog suddenly becomes lethargic, stops eating, vomits, or has diarrhea, that can signal cortisol dropping too low, and it is a reason to pause the medication and call your vet promptly rather than waiting for the next scheduled recheck.
The Bottom Line
Trilostane can give a dog with Cushing’s an excellent quality of life, but only when it is monitored properly. The ACTH stimulation test has been the traditional benchmark; pre-pill cortisol testing is a simpler, well-supported alternative that many vets now favor. Combine whichever your vet uses with careful at-home observation, stick to the recheck schedule, and never adjust the dose on your own.
Sources
- Behrend EN, et al. “Diagnosis of Spontaneous Canine Hyperadrenocorticism: 2012 ACVIM Consensus Statement (Small Animal).” Journal of Veterinary Internal Medicine, 2013.
- “Focus On: Trilostane for Dogs With Hyperadrenocorticism.” Today’s Veterinary Practice, 2021. (PDF)
- Macfarlane L, Parkin T, Ramsey I. “Pre-trilostane and three-hour post-trilostane cortisol to monitor trilostane therapy in dogs.” Veterinary Record, vol. 179, iss. 12, 2016.
- Carvalho MF, et al. “Treatment and monitoring of naturally occurring Cushing’s syndrome by primary care veterinarians in selected European countries.” Journal of Veterinary Internal Medicine, vol. 40, iss. 1, January–February 2026.
- “Trilostane Dosing and Monitoring in Dogs.” MSPCA-Angell.
- “Laboratory assessment of trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism.” PMC7379015.
- Oliver JW. “Steroid Profiles in the Diagnosis of Canine Adrenal Disorders.” Proceedings of the 25th ACVIM Forum, 471–473, Seattle, WA, 2007. (PDF)
