Treatment of Cushing's disease depends on which form of the disease is present. With PDH, the main treatments are medications. Although surgery to remove the pituitary gland or the adrenal glands has been performed, the results with medical treatment are better, and the risk of these surgeries, at least at this time, makes them difficult to recommend.
The drug used most commonly to treat pituitary-dependent Cushing's disease is o,p'-DDD, also known as Lysodren or mitotane. Lysodren is used at first on a daily basis. This drug works by actually causing death of the cortisol-producing cells in the adrenal gland. Dogs without Cushing's disease appear more resistant to the drug's effects than dogs with the illness. Very careful monitoring is necessary once Lysodren has been prescribed. Key factors to observe include thirst, appetite, and general overall disposition. Prior to beginning treatment, the veterinarian may ask that close attention be paid to the dog's appetite and how much food the dog eats. The amount of water a dog drinks over several days should be measured prior to treatment. This helps owners recognize one of the key endpoints of induction treatment: when water consumption drops below 50 milliliters per pound of body weight per day. In some cases, if decreases in appetite, water consumption, or the development of lethargy are not observed, the ACTH stimulation test will be checked after seven days of treatment to see if the endpoint of induction has been reached.
Based on the dog's symptoms and ACTH stimulation test results, a lower dose of the drug is administered during the maintenance phase. Once induction is complete, dogs are given doses of Lysodren, usually two to three times a week, to keep the disease in check. Often, the veterinarian will need to make adjustments in the medication dose according to the recurrence of symptoms during maintenance treatment. Sometimes dogs are given prednisone in addition to Lysodren to avoid adverse consequences of Lysodren treatment, but with very careful monitoring, this additional treatment may not be necessary. Complications during treatment with Lysodren can include the development of signs due to decreased cortisol production from the adrenal glands. These signs, which can be severe and life-threatening if they go unrecognized, include weakness, lethargy worse than the lethargy existing present prior to treatment, loss of appetite, vomiting, diarrhea, and in severe cases, collapse or even shock. Neurological symptoms can occur either as a side effect of Lysodren, or from growth of the pituitary tumor that caused the Cushing's disease in the first place. ACTH stimulation tests are repeated every three to four months to ensure adequate control of the disease.
Dogs treated successfully with Lysodren usually return fairly quickly to normal amounts of water intake, urination, and food intake -- often within seven to 14 days. Strength may improve within a few days to a few weeks, and the appearance of a pot belly may diminish. Skin changes and panting usually take much longer to resolve, as do reproductive disorders. Liver enzyme abnormalities and elevated systemic blood pressure readings may take as long as three to 12 months or more to resolve.
Another drug used for medical treatment of PDH is Anipryl, or L-deprenyl. This drug is also used to treat older pets with a behavioral disorder called cognitive dysfunction syndrome. The drug works by influencing dopamine concentrations in the central nervous system, which in turn then influence production of ACTH by the pituitary gland. There is controversy as to the effectiveness of this drug. However, since the potential side effects are less severe than those that can occur with Lysodren, it is used in some dogs, particularly geriatric dogs with multiple health problems.
Ketoconazole is another drug used for medical treatment of PDH. It acts by blocking the formation of cortisol in the adrenal glands. It can also be given to dogs with adrenal gland tumors that will not be receiving surgery, or to help control symptoms prior to surgery. Some dogs that cannot tolerate Lysodren can be treated successfully with ketoconazole. Its main side effect is the potential to cause injury to the liver.
In dogs with PDH that have large pituitary gland tumors -- particularly those dogs with neurological signs due to the physical presence of a large pituitary mass -- the primary treatment is radiation therapy to control the growth of the tumor.
Dogs with adrenal tumors can be treated surgically or medically. The main treatment for adrenal tumors is surgical removal. The surgery is technically a very difficult one, with many potential complications during and after the procedure. A surgeon experienced in removing adrenal gland tumors should perform it. After surgery, animals often need to be supplemented with both glucocorticoids and mineralocorticoids, the two primary types of steroids normally produced by the adrenal gland. Sometimes supplementation can be tapered as the remaining adrenal gland begins to function again, but some dogs will require supplementation for life.
Drugs used for the medical treatment of adrenal tumors include Lysodren and ketoconazole. Dogs with large and likely inoperable tumors on x-rays or ultrasound, dogs that are very sick, old, or debilitated, and dogs with suspected spread of a malignant adrenal gland tumor are all candidates for medical treatment, as are pets whose owners cannot afford the surgery.
