The most common treatment for Cushing’s disease in dogs is a daily oral medication called trilostane, which lowers cortisol production and can be continued for the rest of your dog’s life. Surgery is an option in some cases, and the right approach depends on whether the disease originates in the pituitary gland or an adrenal tumor. Most dogs respond well to treatment, with average survival times of two or more years after diagnosis.
Pituitary vs. Adrenal: Why the Cause Matters
About 85% of dogs with Cushing’s disease have a tiny tumor on the pituitary gland at the base of the brain. This tumor sends too many signals to the adrenal glands, telling them to produce excess cortisol. The remaining 15% have a tumor directly on one of the adrenal glands. Treatment options and expected outcomes differ significantly between these two types, so your vet will typically run blood tests and imaging to determine which one your dog has before recommending a plan.
Trilostane: The First-Line Medication
Trilostane (sold under the brand name Vetoryl) is the most widely used treatment and the only FDA-approved medication for canine Cushing’s. It works by blocking an enzyme in the adrenal glands that’s needed to produce cortisol. This doesn’t destroy the glands or cure the underlying tumor. It simply dials down cortisol output, which means your dog will need to stay on the medication indefinitely.
The typical starting dose ranges from about 1 to 3 mg per pound of body weight, given once daily with food. Most dogs show improvement within the first few weeks: excessive drinking and urination taper off, appetite normalizes, and energy levels start to balance out. Your vet will adjust the dose based on blood work, so the first few months involve frequent check-ins until the right level is found.
The most common side effects are reduced appetite, vomiting, lethargy, diarrhea, and weakness. These can sometimes indicate the medication is working too well and cortisol has dropped too low, a condition called iatrogenic Addison’s disease. Signs to watch for include sudden loss of appetite, vomiting, tremors, or unusual weakness. If you notice these, stop the medication and contact your vet immediately. This complication is treatable when caught early, but it can become a medical emergency if ignored.
Monitoring During Treatment
Trilostane isn’t a set-it-and-forget-it medication. Your vet will schedule a blood test called an ACTH stimulation test at regular intervals, especially during the first few months. This test measures how your dog’s adrenal glands respond to a hormone signal and confirms cortisol is in the target range. The blood draw needs to happen 4 to 6 hours after your dog takes their trilostane capsule, so you’ll need to time the morning dose around the appointment.
Expect blood tests roughly every two to four weeks when starting treatment, then every three to six months once your dog is stable. These tests typically cost a few hundred dollars each. The medication itself runs anywhere from $30 per month for a compounded version to $80 or more for the brand-name capsule, depending on your dog’s size and dose. Some owners report total monthly costs around $300 when medications and monitoring are combined, so it’s worth asking your vet about compounded options if cost is a concern.
Mitotane: An Older Alternative
Before trilostane became the standard, a drug called mitotane was the primary treatment. It works very differently: rather than blocking cortisol production, it actually destroys portions of the adrenal gland tissue. This makes it more powerful but also riskier. Treatment begins with a “loading phase” of daily doses for a week or two, followed by a lower maintenance dose given just a few days per week.
Because mitotane physically damages adrenal tissue, the margin for error is narrower. Too much can wipe out the adrenal glands entirely, causing a permanent Addisonian crisis that requires lifelong hormone replacement. Side effects during treatment include weakness, vomiting, diarrhea, and loss of appetite. Mitotane is still used in cases where trilostane isn’t effective or isn’t tolerated, but most vets now reach for trilostane first.
Surgery for Adrenal Tumors
When Cushing’s is caused by an adrenal tumor, surgical removal of the affected gland (adrenalectomy) offers the possibility of a cure. If the tumor is benign and hasn’t spread, removing it can resolve the disease entirely. Dogs that survive the surgery have an average survival time of 1.5 to 4 years. The catch is that adrenalectomy carries a 10 to 25% mortality risk during or shortly after the procedure, largely because these dogs are in a fragile metabolic state and the surgery is complex.
For pituitary-dependent cases, a specialized brain surgery called transsphenoidal hypophysectomy can remove the pituitary tumor. This is only available at a handful of veterinary referral centers. When successful, it offers the longest survival times of any treatment, averaging 2 to 5 years. Outcomes are better in dogs with smaller tumors and younger age. After surgery, dogs typically need lifelong hormone replacement therapy since the pituitary gland controls several critical hormones beyond just cortisol.
Selegiline: Limited Effectiveness
Selegiline is an FDA-approved option for pituitary-dependent Cushing’s that works through the brain rather than the adrenal glands. It increases dopamine levels, which in theory suppresses the signal that drives excess cortisol production. In practice, it only works for a small subset of dogs. Only about 20% of pituitary Cushing’s cases involve the specific part of the gland that responds to dopamine. For the other 80%, selegiline has little meaningful effect on cortisol levels. Most veterinarians consider it a secondary option at best.
Melatonin and Lignans for Mild Cases
For dogs with mild symptoms or atypical Cushing’s where other hormones besides cortisol are elevated, some veterinarians recommend a combination of melatonin and flax hull lignans. Melatonin helps inhibit certain enzymes involved in hormone production, while lignans have a mild plant-estrogen effect that can counterbalance elevated sex hormones. Dogs under 30 pounds typically receive 3 mg of melatonin twice daily, while larger dogs get 6 mg twice daily. Lignans are dosed by weight.
This approach is gentler and carries fewer side effects, but it takes at least four months before you can judge whether it’s working. It’s not a replacement for trilostane in dogs with significant symptoms like severe drinking, urination, or muscle wasting. It’s most useful as a first step in borderline cases or as a supplement alongside conventional medication.
Dietary Adjustments
Cushing’s disease causes the body to store excess fat and can weaken muscles over time. A diet lower in fat (under 12% on a dry matter basis) and moderate in fiber (8 to 17%) can help manage weight gain. Protein should come from highly digestible sources like egg whites, chicken, beef, or organ meats to support muscle maintenance. These dietary changes won’t treat the disease on their own, but they can improve your dog’s comfort and body condition alongside medication.
What to Expect Long-Term
With medical treatment using trilostane or mitotane, dogs with pituitary-dependent Cushing’s live an average of 2 to 2.5 years after diagnosis. Surgical options can extend that to 2 to 5 years for pituitary cases. For adrenal-dependent Cushing’s, surgical removal of the tumor offers the best long-term outlook at 1.5 to 4 years, while medical management alone averages about a year.
Many dogs do well on treatment for years, with their symptoms well controlled and a good quality of life. The key is consistent monitoring and dose adjustments. Cushing’s is a chronic condition that requires ongoing attention, but it’s one of the more manageable hormonal disorders in veterinary medicine. Most owners find that once the initial stabilization period is behind them, the routine becomes predictable.