Trilostane — sold under the brand name Vetoryl — is the most commonly prescribed medication for Cushing's disease in dogs. It's the only FDA-approved drug for treating both pituitary- and adrenal-dependent Cushing's, and it's genuinely effective at managing cortisol levels.
But it comes with a real side effect profile that owners deserve to understand clearly. This isn't a post arguing against trilostane. It's information every owner using it — or considering it — should have.
How Trilostane Works
Trilostane works by blocking an enzyme (3β-hydroxysteroid dehydrogenase) that the adrenal glands need to produce cortisol. Less enzyme activity means less cortisol. It's effective, but the margin between sufficient suppression and too much suppression is narrow — which is why regular monitoring is essential.
Common Side Effects
The most frequently reported side effects include:
· Lethargy and weakness, particularly in the first few weeks
· Reduced appetite or vomiting, especially shortly after dosing
· Diarrhea or loose stools
· Increased thirst and urination that can initially worsen before improving
· Muscle weakness or wobbliness
These are often dose-related and may improve with dose adjustment. Most vets recommend an ACTH stimulation test at 10–14 days after starting, again at 30 days, and every 3–6 months ongoing.
Serious Side Effects
More serious complications can occur. Owners should know what to watch for:
Hypoadrenocorticism (Addison's disease): This happens when trilostane suppresses cortisol too aggressively. Symptoms include severe weakness, collapse, vomiting, diarrhea, and shaking. This is a medical emergency — contact your vet immediately.
Adrenal necrosis: In rare cases, trilostane can cause destruction of adrenal gland tissue. This can be life-threatening and is more likely in dogs that are overdosed or under-monitored.
Electrolyte imbalances: Because the adrenal glands regulate sodium and potassium alongside cortisol, disrupting their function can affect electrolyte balance, particularly in dogs with underlying kidney issues.
Warning Signs to Watch For
· Sudden extreme weakness or inability to stand
· Collapse or unresponsiveness
· Vomiting or diarrhea that appears suddenly and is severe
· Complete loss of appetite
· Shaking or shivering without obvious cause
Any of these on trilostane warrant an immediate vet call. Don't wait.
Why Some Owners Look for Alternatives
Many owners choose to pursue natural management — or combine natural supplements with a lower trilostane dose — because:
· Their dog has had a serious adverse reaction to trilostane
· The ongoing cost of the medication and monitoring is prohibitive
· Their dog's Cushing's is mild and pharmaceutical intervention feels disproportionate
· They want to reduce medication load in an older dog already on multiple prescriptions
Can You Use Lignans Alongside Trilostane?
In many cases, yes — but always with your vet's guidance. Some owners maintain control at a lower trilostane dose when also giving lignans and melatonin. The protocols aren't mutually exclusive, and for some dogs, combining them provides more comprehensive symptom management than either alone.
If you're wondering what type of lignan may be right for your dog, check out or recent article here.
For more on what vet-recommended treatment options look like: Cushings In Dogs — Vet Recommended Treatments
Sources:
• FDA — Treating Cushing's Disease in Dogs
• VCA Animal Hospitals — Cushing's Disease in Dogs