Cushing’s Disease in the Dog- Medical Treatment

Several medications have been developed to manage Cushing’s Disease in Dogs. The first was a derivative of DDT called Lysodren, trade name Mitotane (chemical name ortho para prime DDT). This medication has been used successfully for thousands of dogs over the years. More recently, other medications have been developed to reduce the cost and side effects associated with treating Cushings Disease in dogs. Regardless of drug selection, the main goal of treatment is to reduce the overt clinical signs of the disease, including excessive thirst, urination and appetite. Treatment is also aimed at decreasing hair loss and promoting new hair growth, reversing immune suppression, as well as preventing blood clots (Pulmonary Thromboembolism).  Click here for a more thorough review of Clinical Signs of Cushing’s Disease in Dogs.


Medical Treatment for Cushing's Disease in the DogLysodren is a pill used to selectively damage or destroy adrenal gland cells that produce excess cortisol in dogs with Cushing’s Disease. It has been most commonly used to treat dogs with the pituitary-dependent form of Cushings Disease (PDH), though, when used at higher doses, can be effective in treating adrenal tumors that produce excess cortisol as well (ADH). Because Lysodren damages the cells, it is important to monitor cortisol levels frequently with blood tests at first to prevent excessive destruction, which would cause dangerously low cortisol levels. Treatment protocols typically involve a single daily dose of Lysodren to establish normalized cortisol levels (remission), followed by weekly or bi weekly treatment. Careful observation for the first signs of decreased drinking can help identify when cortisol levels are decreasing and when remission is accomplished.  Once stable, blood monitoring intervals can be prolonged and at-home monitoring of drinking and appetite become key.
Side effects of treatment of dogs with Cushing’s Disease with Lysodren can include mild irritation of the stomach, sometimes resulting in vomiting, which is usually easily controlled by giving the drug less often. Less commonly, but of greater import, are signs of overdose and dangerously low circulating cortisol.  Whereas signs of healthy induction of remission include decreased drinking and appetite, these may progress to profound weakness, vomiting, and occasionally shock, requiring hospitalization and emergency intervention. Timely replacement of cortisol either orally or intravenously usually results in a rapid return to normal in these latter cases.  In the majority of dogs that are well balanced on Lysodren, a small amount of replacement cortisol in the form of prednisone may be necessary for normal physiologic function during periods of stress, such as boarding, hospitalization, or surgery.
The long term prognosis of dogs with Cushing’s Disease with Lysodren is generally good. Published articles state that 50 % of dogs live 2 years after diagnosis (Kintzer PP, Peterson ME, et al. Mitotane treatment of 200 dogs with pituitary-dependent hyperadrenocorticism. JVIM 1991;5:182-190). However, most dogs with Cushing’s Disease are older and may have other diseases of aging.  Dogs that are well-controlled with Lysodren, therefore most often die of diseases other than Cushing’s or its treatment.


Trilostane is a medication approved by the FDA to treat PDH and ADH in dogs.  It inhibits the production and release of cortisol from normal and adrenal tumor production of cortisol, though to a much lesser extent in the latter. This is in contrast to Lysodren which selectively destroys cortisol-producing cells of the adrenal glands. This action can typically be reversed by stopping the medication in case of minor side effects.  Many veterinarians and clients therefore favor Trilostane over Lysodren to treat Cushing’s Disease in Dogs.  Trilostane comes as a daily capsule and is well-tolerated by most dogs, improving abnormal drinking and urination in 70% of canine patients (Scott-Moncrieff, CJ. “Update on Treatment of Hyperadrenocorticism: What is the Current Recommendation?” Proceedings: Forum ACVIM 2010).
Though typically mild, side effects occur in about two thirds of dogs treated with trilostane.  Side effects can include lethargy, vomiting, and/or diarrhea and usually resolve on their own within several days.  In rare instances, Trilostane has caused severe, rapid death of the adrenal gland, leading to life-threatening illness.  In still others, cortisol levels may dip too low, leading to a condition known as Addison’s Disease (hypoadrenocorticism), requiring cortisol supplementation (in the form of prednisone).  It is important to evaluate cortisol levels 10, 30 and 90 days after starting treatment, as well as 30 days after adjusting the dosage.  In one study, average life expectancy for dogs with PDH treated with Trilostane was 930 days from the time of diagnosis (Alenza DP, et al. Long-term efficacy of trilostane administered twice daily in dogs with pituitary dependent hyperadrenocorticism. JAAHA 2006;42:269-276).

Other Drugs

Other drugs that have some use in dogs with Cushing’s disease include Ketoconazole, an antifungal agent, and l-deprenyl, which increases brain dopamine concentrations.  Both of these medications are more useful for PDH than ADH.

In addition to medical treatment of Cushing’s Disease, there are also surgical and radiation treatment options available. Click here to learn more.

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Dr Roger Johnson and Dr Derek Calhoon

Roger K. Johnson, DVM, Diplomate ACVIM (internal medicine) is a board-certified veterinary internal medicine specialist. His professional interests include cardiology as well as using advanced diagnostics to help his patients. His particular favorites include echocardiography, abdominal ultrasonography, and endoscopy. Derek Calhoon, DVM is a veterinary general practitioner.

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