Hyperadrenocorticism (Cushing's syndrome)
What is Cushing's syndrome?
Hyperadrenocorticism or Cushing’s syndrome is a clinical condition that results from an overproduction of cortisol by the adrenal glands. This overproduction most commonly results from a benign tumor in the pituitary gland, which is located at the base of the brain. Under normal conditions, the pituitary gland is responsible for stimulating the adrenal glands to produce cortisol by releasing a hormone called adrenocorticotrophic hormone (ACTH). Once a sufficient amount of cortisol is released into the body, the release of ACTH from the pituitary gland is turned off. Tumor cells in the pituitary don’t respond appropriately to the signals to shut down and they continue to secrete ACTH and the adrenal glands continue to produce cortisol in response. According to statistics, in less than 20% of pets diagnosed with Cushing’s disease, the excess production of cortisol results from a tumor in one of the adrenal glands. Like tumor cells in the pituitary, these cells don’t respond normally to signaling and continue to produce cortisol without the stimulation by ACTH. Cushing’s syndrome is relatively common in dogs and rare in cats.
What are the clinical signs of Cushing's syndrome?
There are many clinical signs that might be seen with Cushing’s syndrome. These include increased water consumption and urination, ravenous appetite, pot bellied appearance, thin skin, muscle wasting or weakness, ligament tears (commonly the cruciate ligaments of the knees), hair loss, panting, lethargy, recurrent urinary tract infections or neurological abnormalities. Many pets exhibit several of the listed clinical signs, but rarely does any one pet have all of the signs. Cats with Cushing’s syndrome are often diabetic and also have very thin skin that tears easily.
How is Cushing's syndrome diagnosed?
Your veterinarian will likely have an index of suspicion that your pet has Cushing’s syndrome based on the history you provide about your pet and by physical examination. Routine blood work and a urinalysis may be recommended to evaluate for changes that might be consistent with Cushing’s as well as to ensure there isn’t evidence of problems with other organs such as the liver and kidneys or evidence of a urinary tract infection. More specialized blood tests will likely be recommended, which are used specifically for diagnosing Cushing’s as well as differentiating between adrenal and pituitary dependent Cushing’s syndrome. Your veterinarian may also recommend diagnostic tests such as radiographs and ultrasound to evaluate the size of the adrenal glands and to look for evidence of a mass associated with one of the glands. If your pet is exhibiting neurological signs, a CT scan or MRI might be recommended to evaluate the size of the pituitary gland. Although most pituitary tumors remain small, some can increase in size and cause pressure on the brain resulting in neurological signs, the most common being blindness and seizures. These larger pituitary tumors are called macroadenomas.
How is Cushing's syndrome treated?
Although we are unable to cure Cushing’s syndrome, many pets can be managed with medical or surgical treatment. The method of treatment for Cushing’s syndrome largely depends on whether the cause is pituitary dependent or a tumor of the adrenal gland. Adrenal tumors can sometimes be removed surgically, and in some cases, may be treated medically. Consultation with your veterinarian regarding the nature of your pet’s tumor will help you make the best decision regarding treatment for your pet. Pituitary tumors are most commonly treated with a medication called O,P’-DDD, (Mitotane or Lysodren). This drug was originally produced as an insecticide, but was found to chemically destroy the region of the adrenal gland responsible for the excess cortisol production. This drug is very effective in dogs, but not in cats, therefore surgical removal of one or both adrenal glands is the treatment of choice in cats.
If treatment with Mitotane is initiated, you and your veterinarian will need to monitor your pet very closely while on this medication, as it can have toxic effects. Signs to watch for at home include an attitude change or lethargy, development of vomiting or diarrhea or a decrease in appetite or water consumption. The first phase of Mitotane therapy is termed the “induction phase” and your pet will be taking the medication daily. The goal of this phase of therapy is to destroy enough adrenal tissue so that only minimal amounts of cortisol are being produced. This phase usually takes from 3 to 7 days, but can take as little as 1 day or up to 2 weeks in some patients. Your veterinarian will want to monitor this induction phase with blood tests. Once the induction phase is completed, your pet will be started on a maintenance protocol, which is aimed to maintain cortisol production within a certain range. Blood work will need to be checked periodically and the dosage of medication may need to be adjusted from time to time.
Ketoconazole is an antifungal medication, which interferes with the production of cortisol. This medication is much more expensive than Mitotane and often less effective, but it is a viable alternative, especially in the short term if the pet requires surgery or if there is an adrenal tumor that is too large or invasive to be removed.
L-Deprenyl (Anipryl) is another medication that might be recommended for some pets with pituitary dependent Cushing’s syndrome. This medication may help to alleviate some of the clinical signs by decreasing the amount of ACTH released from the pituitary gland. This medication hasn’t proven to be effective in all pets with pituitary disease and doesn’t suppress cortisol production like Lysodren does, but it has the benefit of being less toxic.
If your pet is diagnosed with a macroadenoma, radiation therapy might be recommended in hope of decreasing the size of the tumor, thus reliving some of the pressure on the brain and the related clinical signs. Radiation therapy hasn’t been successful in decreasing the production of ACTH by the tumor so concurrent therapy with Mitotane is still recommended.
If treatment with Mitotane is initiated, you and your veterinarian will need to monitor your pet very closely while on this medication, as it can have toxic effects. Signs to watch for at home include an attitude change or lethargy, development of vomiting or diarrhea or a decrease in appetite or water consumption. The first phase of Mitotane therapy is termed the “induction phase” and your pet will be taking the medication daily. The goal of this phase of therapy is to destroy enough adrenal tissue so that only minimal amounts of cortisol are being produced. This phase usually takes from 3 to 7 days, but can take as little as 1 day or up to 2 weeks in some patients. Your veterinarian will want to monitor this induction phase with blood tests. Once the induction phase is completed, your pet will be started on a maintenance protocol, which is aimed to maintain cortisol production within a certain range. Blood work will need to be checked periodically and the dosage of medication may need to be adjusted from time to time.
Ketoconazole is an antifungal medication, which interferes with the production of cortisol. This medication is much more expensive than Mitotane and often less effective, but it is a viable alternative, especially in the short term if the pet requires surgery or if there is an adrenal tumor that is too large or invasive to be removed.
L-Deprenyl (Anipryl) is another medication that might be recommended for some pets with pituitary dependent Cushing’s syndrome. This medication may help to alleviate some of the clinical signs by decreasing the amount of ACTH released from the pituitary gland. This medication hasn’t proven to be effective in all pets with pituitary disease and doesn’t suppress cortisol production like Lysodren does, but it has the benefit of being less toxic.
If your pet is diagnosed with a macroadenoma, radiation therapy might be recommended in hope of decreasing the size of the tumor, thus reliving some of the pressure on the brain and the related clinical signs. Radiation therapy hasn’t been successful in decreasing the production of ACTH by the tumor so concurrent therapy with Mitotane is still recommended.
What are the side effects of Mitotane?
Side effects from the drug are most commonly associated with a rapid drop in cortisol levels. If too much of the adrenal gland is destroyed by the medication, your pet will likely show signs such as decreased appetite, lethargy, vomiting, diarrhea or instability while walking. It is very important to report these signs to your veterinarian if they occur. These side effects are reversed quite easily in most patients by supplementing the pet with corticosteroids such as prednisone. In rare cases, it is possible to permanently destroy the adrenal glands with Mitotane and these pets will require therapy with medications to replace the cortisol and other steroid hormones normally produced by the adrenal glands. Some veterinarians may choose to give low doses of cortisone with the Mitotane in attempt to prevent these clinical signs from developing. Some veterinarians may also choose to treat their patients to the extent that the adrenal gland is destroyed, creating Addison’s disease.
What can I expect if I choose not to treat my pet?
The effects of excess cortisol will eventually be detrimental to your pet’s health. Too much cortisol suppresses the immune system, making the pet more susceptible to infections. Urinary tract infections are common and infections that start in the bladder can migrate to the kidneys resulting in pyelonephritis, which may cause permanent kidney damage. Excessive cortisol can also result in an increased risk for stone formation in the urinary tract, diabetes mellitus and PTE. Pulmonary thromboembolism (PTE) is the development of blood clots in the lungs and this condition is often fatal. Pets with Cushing’s syndrome also have a decreased ability to heal after surgery or injury. Pets with adrenal tumors are at risk for local spread of the tumor. Adrenal tumors can be invasive and can grow into other organs or tissues in the abdomen. Although there are risks involved with treating Cushing’s syndrome, the disease, itself is often more detrimental to the pet’s health and the risks involved with not treating outweigh those of treatment.
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