Hyperadrenocorticism (Cushing's Disease)

What Causes Cushing's Disease? The pituitary gland, located within the brain, acts like the master gland of the body. It makes hormones that control other glands, two of which are the adrenal glands, paired glands located next to the kidneys. These glands make glucocorticoids which, when produced in excess, cause the signs of Cushing's. It is the equivalent of the body making its own source of steroids, such as prednisone, in excessive amounts. Signs of Cushing's These usually include thinning of the hair and skin changes; pot-bellied appearance; increased water consumption; increased urination; increased food intake; panting; weakness and fatigue. Pets may show some or all of these signs. If this condition is not treated, diabetes, hypertension, clot formation (embolism) and infections can result. Dogs are usually affected, but occasionally, cats, especially diabetic cats, can have this as a concurrent illness. The Pituitary Gland & Cushing's Disease This is the most common form of Cushing's. It is associated with a usually benign tumor that secretes a hormone that causes the adrenals to stay "on" all the time. This form of Cushing's is responsive to medical treatment. Occasionally, these tumors can get large enough to increase pressure in the brain and cause neurological signs (personality changes, seizures, circling). The Adrenal Gland & Cushing's Disease This is the less common form of Cushing's. It is associated with a benign or malignant tumor of the adrenal gland. This form is less responsive to medical treatment and often requires surgery to treat. Diagnosis of Cushing's Initially, some indications of this disease can be noted on a complete blood panel. But more specific tests to diagnose Cushing's include an ACTH stimulation test and/or a low dose dexamethasone suppression test. These tests usually indicate if the dog has Cushing's or not. Other tests must be done such as a high dose dexamethasone suppression test, measurement of endogenous ACTH or an abdominal ultrasound to differentiate between pituitary and adrenal based tumor. This is important to do since these conditions are treated differently. Treatment For the pituitary gland tumor, treatment is done with either lysodren, ketoconazole, anipryl, or trilostane. For the adrenal gland tumor, treatment can be medical with lysodren or ketoconazole or surgery. Your veterinarian will discuss the benefits and drawbacks of each form of treatment to decide what is best for your pet. Lysodren (Op,DDD, Mitotane) This is a drug that selectively kills the adrenal gland cells so that less steroids are produced. This is given at a higher dose initially (the induction period) twice daily, and then at a lower dose 1-3 times a week for maintenance and control of the disease on an ongoing basis. Especially when given at higher doses, this drug has potential side-effects among which are vomiting, diarrhea and loss of appetite. Occasionally, if this drug works too well, too much of the adrenal glands are killed, resulting in a loss of ability to make steroids. However, this condition, called Addison's or hypoadrenocorticism, is medically manageable. Lysodren tends to be expensive, especially in the initial period since more of it is being given; it is less costly at maintenance levels when lower amounts are being given. Side-effects can occur with use of this drug so that your veterinarian will want to closely monitor your pet, especially during the induction period. Such side effects should be reported immediately as these may indicate a need to reduce the dosage of the medication or stop it altogether. It is important with this drug that enough is given to control the disease but not too much is given to avoid making the animal ill. An ACTH stimulation test helps to monitor the animal's response to the lysodren and should be done at the end of the induction period, then again about a month after starting onto the maintenance therapy and then every 4-6 months thereafter. With lysodren for most dogs, this maintenance regime with lysodren will control the disease; however, there may be relapses and then the induction phase must be repeated. In addition to doing the ACTH stimulation tests to monitor response to lysodren, your veterinarian will also want to do general blood tests and urine cultures on a regular basis, about every 6 months. Treatment and monitoring are life-long. Ketaconazole (Nizoral) This drug interferes with the body's steroid production, and it must be given twice a day on an ongoing basis. Side-effects of this drug include lethargy, vomiting, decreased appetite and occasionally, liver disease. Your veterinarian will want to monitor your pet's response with blood and urine tests done on a regular basis. Treatment and monitoring are life long. L-deprenyl (Anipryl/Selegiline) This drug helps to normalize dopamine levels and indirectly controls pituitary function. This drug also has antioxidant and neuroprotective properties and is often used in the treatment of canine cognitive dysfunction ("senility"). This medication is given once daily in the morning on an ongoing basis. A low dose is initiated, and depending on the animal's response, the dose may be increased. Side-effects are rare but can include vomiting, diarrhea, decreased energy and restlessness. While there are no specific changes in the blood or urine that occur with the treatment of anipryl, your veterinarian will want to monitor your pet with blood and urine tests on a regular basis for infections and other problems that might arise during treatment. Treatment and monitoring are long-term with general blood and urine tests done on a regular basis although specific tests to monitor the animal's hormone status such as ACTH stimulation test are not needed. Trilostane (Modrenal/Vetoryl) This relatively new drug interferes with steroid production and works well in an estimated 80% of dogs with pituitary based disease. It is given once or twice daily on an ongoing basis, and improvement with water intake and urine output is usually noticed within a few weeks. Improvement with coat, skin condition and muscle tone occurs later. Side-effects are few but include decreased appetite and lethargy, and reducing the dose or stopping the drug allows for quick resolution of these signs. Treatment and monitoring are life long as stopping the drug will allow continuation of excessive hormone production. In addition to general blood and urine tests, ACTH stimulation tests are done through the initial period to adjust the dosage, since the effective dosage of trilostane differs markedly amongst dogs. With all drug treatments for Cushing's, immediate improvements may be seen (drinking and urinating less) but about 4-6 months are needed before improvement with the coat and skin can be seen. Medications (Estimated Costs) Lysodren, ketoconazol, anipryl and trilostane are all expensive medications (about $2-5/tablet). At this time, trilostane must be imported from the UK and requires additional paperwork to process with the Food & Drug Administration (FDA). Laboratory tests (Estimated Costs) Either a low dexamethasone suppression test or ACTH stimulation test can be done to diagnose Cushing's and the ACTH stimulation test is done to monitor an animal's response to lysodren and trilostane. Cost for each test is about $130-$250, depending on the dog's weight. General blood profiles and urine cultures are about $90 each. Abdominal ultrasound is $115-$150. Treatment protocol - Lysodren Induction Give ____ of a 500 mg tablet of _________ every _____ hours for approximately ________ days. A meal should be fed twice daily before giving medication. If your animal is slow to eat, doesn't finish the food or refuses its food or its water consumption has dropped to less than ______/day, don't give the medication and contact your veterinarian. The End Point This is when the drug is discontinued at the higher initial dose and a test (an ACTH stimulation test) is done to evaluate the degree of response to the medication. This endpoint varies with every animal so you must be alert for the following changes- decreased water consumption; decreased appetite; vomiting; diarrhea; lethargy. The range of time of response to the drug is 2-35 days, but the majority of dogs will respond within 5-14 days. Maintenance Once the end-point has been achieved, the dog is put on a maintenance level of _____ of a 500 mg tablet every ______ days (Mon. Tues. Wed. Thurs. Fri. Sat. Sun.). It is best given with food. During induction and maintenance with Lysodren, there is potential for problems with the medication (when your dog has vomiting, diarrhea or acting listless). Prednisone can help to counteract these side-effects. Your veterinarian will talk to you if this treatment will be necessary. Treatment protocol - Ketoconazole Give ____ of 500 mg tablet 2 times/day. It is best given with food. Treatment protocol - Anipryl Give ____ of a _______mg tablet 1 time/day in the morning. Treatment protocol - Trilostane According to body weight, dogs are started on specific doses. However, based on the animal's clinical response and the results of the ACTH stimulation tests, these doses may be increased or decreased accordingly. Dogs less than 5 kg receive 30 mg once daily, dogs 5-20 kg receive 60 mg once daily and dogs greater than 20 kg receive 120 mg once daily. Some dogs respond better when the total dosage is divided into twice daily. It is best given with food. This drug is given on an ongoing basis since cessation of its administration will allow the body's continued excessive hormone production. It is available in 60 mg and 120 mg capsules so that for small dogs it may be necessary to split the 60 mg capsules into smaller gelatin capsules. The drug should be stored in airtight, light resistant containers, and pregnant women should wear gloves when handling the drug. All users should wash their hands after handling the drug. An ACTH stimulation test may need to be done at 2, 4 and 6 weeks into treatment and then done every 6-12 months, depending on each individual's response. This test needs to be done within 2-6 hours after trilostane has been given (this timed factor is not a concern for the ACTH stimulation test done when dogs are treated with lysodren). If you have questions regarding this disease or its treatment, don't hesitate to contact your veterinarian. The above is general veterinary information. Do not begin any course of treatment without consulting your regular veterinarian. All animals should be examined at least once every 12 months.