Trilostane (sold under the brand name Vetoryl) is the most commonly prescribed medication for dogs with Cushing’s disease. It works by blocking an enzyme the adrenal glands need to produce cortisol, effectively dialing down the excess hormone that causes the disease’s symptoms. A second drug, mitotane (Lysodren), takes a more aggressive approach and is used less frequently. A few other medications exist, but trilostane has become the standard first-line treatment for most dogs.
How Trilostane Works
Trilostane is a synthetic steroid that blocks cortisol production in the adrenal glands. Unlike some treatments that permanently destroy adrenal tissue, trilostane’s effect is reversible. It inhibits the enzyme responsible for converting precursor hormones into cortisol, so when you stop giving the medication, cortisol production gradually returns to its previous level. This reversibility is a significant safety advantage: if your dog has a bad reaction or the dose is too high, the effects wear off.
The starting dose depends on your dog’s weight and the dosing schedule your vet chooses. For once-daily dosing, the typical range is 2.2 to 6.6 mg per kilogram of body weight. Some vets prefer twice-daily dosing at a lower amount, starting around 0.5 to 1 mg per kilogram every 12 hours. The twice-daily approach can provide more stable cortisol suppression throughout the day. Your vet will adjust the dose over the first few months based on blood test results and how your dog is responding.
Most dogs show noticeable improvement within the first few weeks. Excessive drinking and urination typically decrease first, followed by gradual improvements in appetite, energy level, and coat quality over several months. Median survival times in studies of dogs treated with trilostane range from about 17 to 30 months, and research shows an 11% higher survival rate at 36 months compared to the alternative drug mitotane.
What Trilostane Costs
Trilostane is a lifelong medication, so cost matters. A 30-count supply of the smallest capsule (5 mg, for dogs under 10 pounds) runs around $70 to $75 through online pet pharmacies. Larger dogs need higher-strength capsules, and the price increases accordingly. Dogs weighing 44 to 88 pounds take a 120 mg capsule daily, while very large dogs over 88 pounds may need 180 mg. On top of the medication itself, you’ll have regular blood work and vet visits for monitoring, especially in the first year.
Mitotane: The More Aggressive Option
Mitotane works very differently from trilostane. Rather than temporarily blocking cortisol production, it actually destroys portions of the adrenal gland. It targets the specific layers of the adrenal cortex responsible for producing cortisol and related hormones. This makes it more potent but also riskier.
Treatment with mitotane happens in two phases. During the induction phase, your dog receives a relatively high daily dose (typically around 25 mg per kilogram per day) for several days to rapidly reduce cortisol output. You’ll need to watch your dog closely during this period for signs that cortisol has dropped enough, such as decreased appetite or reduced water intake. Once cortisol levels are under control, the dose drops significantly to a maintenance level of roughly 25 to 50 mg per kilogram per week, split across a few days.
Mitotane was the standard Cushing’s treatment before trilostane became available, and it still has a role. Some vets reach for it when trilostane isn’t controlling the disease adequately, or for dogs with adrenal tumors where a more destructive effect on adrenal tissue is desirable. Studies comparing the two drugs show similar overall survival times, but trilostane produces fewer and milder side effects, which is why it has become the preferred choice for most cases.
Other Medications
Ketoconazole, an antifungal drug, can also suppress cortisol production and is sometimes used as an alternative when trilostane and mitotane aren’t options. Treatment starts at a low dose of 5 mg per kilogram twice daily for a week, then increases to 10 mg per kilogram twice daily. About half of dogs that respond to ketoconazole eventually need an even higher dose of 15 mg per kilogram twice daily to stay controlled. It’s generally well tolerated, with low toxicity and minimal effect on other important hormones, but it’s considered less effective overall than trilostane or mitotane.
Selegiline (L-Deprenyl), a drug that affects brain chemistry, was once marketed for pituitary-dependent Cushing’s disease. The idea was that it could reduce the abnormal hormone signals coming from the pituitary gland. In practice, it hasn’t held up. A study of ten dogs treated with selegiline for six months found that only two showed meaningful clinical improvement, four actually got worse, and four stayed the same. Blood tests measuring cortisol and adrenal function showed no significant changes. It’s not recommended as a primary treatment.
How Treatment Differs by Type
About 80% of dogs with Cushing’s disease have the pituitary-dependent form, meaning a small tumor in the pituitary gland is overproducing the hormone that tells the adrenal glands to make cortisol. The remaining 20% have an adrenal tumor producing cortisol on its own. Both types respond to trilostane, which works directly at the adrenal gland regardless of what’s driving the excess production.
For adrenal tumors, surgery to remove the affected gland is sometimes the best option if the tumor hasn’t spread. When surgery isn’t possible, both trilostane and mitotane can manage the disease medically. Research comparing the two drugs specifically in adrenal-dependent cases found no significant difference in survival time, but trilostane’s milder side effect profile makes it the preferred medical option here too.
Monitoring During Treatment
No matter which medication your dog takes, regular blood testing is essential. The primary monitoring tool is a stimulation test that measures how the adrenal glands respond when challenged. For dogs on trilostane, this test needs to be timed carefully, starting 4 to 6 hours after the morning dose, when the drug’s effect is near its peak. Your vet will typically run this test at 10 days, 4 weeks, and 12 weeks after starting treatment, then every 3 to 6 months once the dose is stable.
The biggest risk with any Cushing’s medication is pushing cortisol too low. This creates a condition called iatrogenic hypoadrenocorticism, essentially the opposite of Cushing’s disease. Watch for loss of appetite, vomiting, diarrhea, weakness, lethargy, or shakiness. These signs can appear at any point during treatment, not just when starting a new dose. If your dog develops any of these symptoms, stop the medication and contact your vet. Because trilostane’s effects are reversible, most dogs recover quickly once the drug is withheld and the dose is adjusted downward.
Long-Term Outlook
Cushing’s disease is manageable but not curable with medication. Dogs on trilostane generally do well for years. Studies report median survival times ranging from roughly 18 months to 30 months after starting treatment, though many individual dogs live considerably longer. Trilostane’s reversible action and favorable safety profile make it particularly well suited for long-term use, including in dogs that also have diabetes, kidney problems, or heart disease.
The first few months of treatment require the most hands-on involvement as your vet fine-tunes the dose. After that, the routine settles into daily medication and check-ups every few months. Most owners notice a significant quality-of-life improvement: less frantic drinking and urinating, better energy, a healthier coat, and a dog that generally acts more like itself again.