cushings-disease-in-dogs[/caption]Cushing’s Disease in Dogs
If your older dog is drinking and urinating more than usual, it could be caused by a variety of reasons. One cause your veterinarian may test for is Cushing’s disease (CD), also known as hyperadrenocorticism. This condition, usually caused by a tumor in the pituitary gland, is far more common than we realize, but because of the complex diagnostic testing required, it’s underdiagnosed. Treatment is expensive and ongoing, and it requires consistent monitoring.
You may have heard of the stress hormone cortisol and the associated “fight or flight" response. Cortisol is controlled by the adrenal cortex, located on the outer layer of adrenal glands. These two peanut-sized glands, situated in front of the kidneys, produce hormones to help the body perform essential functions.
The pituitary gland, a tiny gland found at the base of the brain, releases adrenocorticotrophic hormone (ACTH), which in turn tells the adrenal glands to release cortisol, also called glucocorticoids. In a pet with CD, a tumor in the pituitary gland or, less commonly, in one of the adrenal glands, causes the cortex to release an excess amount of cortisol.
Symptoms of Cushing's Disease in Dogs
- Often owners report that their first clue that something might have been wrong was their dog wanting to go out at night to urinate.
- The disease causes extreme thirst, so a dog with CD tends to drink tremendous amounts of water and urinate frequently.
- As the disease progresses, dogs lose muscle and become weak.
- Owners might notice a thinning of the skin, lesions on the skin, and hair loss on the flanks, neck, and perineum.
- Obesity and lack of energy are also symptoms.
Because it takes time — at least one year — for these symptoms to develop, and because the symptoms are often mistaken for common signs of aging, many dogs have the advanced form of CD before the owner even recognizes a problem exists.
Causes of Cushing's Disease in Dogs
Cushing’s disease is a naturally occurring syndrome, but it can also be caused by administering excessive amounts of prednisone or dexamethasone for prolonged periods. Chronic application of steroid-containing ear drops can also cause the condition because the medication is absorbed through the skin. Affected dogs develop symptoms that are identical to those of the tumor-based disease. This form resolves once the steroids are stopped.
Certain breeds are at a higher risk of developing CD. The Poodle, Dachshund, Boston Terrier, Boxer, and Beagle are some breeds to watch. Almost all patients are older than eight years when CD develops.
Diagnosis of Cushing's Disease in Dogs
Diagnosing CD is not easy and can be quite expensive. When a veterinarian suspects this disease, blood and urine tests are needed to make the diagnosis. Dilute urine and an elevation of the liver enzyme alkaline phosphatase in the blood indicate that testing for CD may be necessary.
Cushing’s disease can be verified with an adrenocorticotropic hormone (ACTH) stimulation test. For this test, a blood sample is drawn from the patient, then he is given an injection of ACTH, and a second blood test is taken a few hours later. If the dog’s cortisol level goes up a little, his adrenal response is normal. If it starts high and climbs even higher, a diagnosis of CD is confirmed.
The veterinarian may also use a second method, the dexamethasone suppression test, in which the dog receives an injection of the steroid dexamethasone. In a healthy dog, the cortisol level goes down over the following few hours because the steroid suppresses adrenal production. If the cortisol level fails to drop, it suggests there is a tumor not responding to the medication.
Ultrasound examinations also allow the veterinarian to determine whether or not a tumor is present, and if it’s located in the pituitary gland or the adrenal glands.
Treatment of Cushing's Disease in Dogs
The location of the tumor dictates which treatment to use. More than 90 percent of dogs with CD have a pituitary-gland tumor. This type of tumor is only millimeters in size and is often benign, but it’s problematic because it manufactures and releases uncontrolled quantities of ACTH, which, as explained above, stimulates the adrenal cortex to release excessive amounts of cortisol.
Though pituitary tumors are routinely removed in people, this surgical technique is still in its infancy in dogs. We treat most dogs with pituitary-based CD with medication. Mitotane (Lysodren) and trilostane (Vetoryl) are oral medications that selectively destroy part of the adrenal cortex so that although the pituitary gland tumor continues to release ACTH, cortisol levels remain normal. Careful monitoring is required to ensure that the drugs don’t destroy all of the cortex and that the cortisol stays at a defined level.
Adrenal-based CD, which thankfully is the rare form of the disease, is more concerning and best treated with surgery. About one-half of these tumors are malignant, growing aggressively and metastasizing quickly. Surgical excision of a malignant adrenal tumor is unlikely to be curative. If it is a benign growth, surgery may cure it, but the surgery is a complicated procedure.
Once treatment has been initiated, the symptoms of CD should begin to dissipate, starting with a decrease in drinking in one week or so. It takes a little longer (several months) for the skin lesions to resolve.
Prognosis for Dogs With Cushing's Disease
The average survival time for a dog with CD is about two years, with only 10 percent of patients living beyond the four-year mark. This statistic, however, does not mean that this disease causes death. Because CD is most often diagnosed in geriatric dogs, most die of unrelated causes brought on by aging.
Cushing's disease
Cushing's disease can trouble older dogs
Animal bodies are a marvel of interactions between organs and systems kept in balance by the production of enzymes that aid in metabolic processes and hormones that regulate body functions. When the balance is disturbed by illness, injury, or advancing age, the body goes awry: appetite and water consumption may change, organs may malfunction, or medication to treat one illness may cause another.
Such is the case with Cushing's disease, also known as hyperadrenocorticism, the production of excess hormones from the adrenal glands. Cushing's disease usually strikes older dogs with a bucket-full of symptoms that can mimic other diseases. Increased appetite, increased drinking and urination, panting, high blood pressure, bulging abdomen, skin lumps and discoloring, hair loss, muscle weakness, and nervous system disorders can occur with the disease.
Located above the kidneys, the adrenals produce cortin, a complex of steroid hormones - including cortisone and cortisol - that help regulate body weight, mineral balance, the structure of connective tissue, some white blood cell production, and skin health. Adrenocorticotropic hormone (ACTH) from the pituitary gland stimulates the adrenal glands to produce cortin. Presence of a tumor on either the adrenal glands or pituitary can cause the adrenals to run amok and trigger Cushing's by producing an excess of cortin.
Diagnosis
The symptoms may creep up on the pet and pet owner. Pets do not appear to be critically ill because the danger signs of vomiting, diarrhea, pain, seizures, and bleeding do not occur. To the contrary, the symptoms often appear to be connected to normal aging. Muscle weakness also causes lethargy and a reduced tolerance for exercise, both of which are typical in aging dogs and cause no alarm in owners. Often owners do not seek veterinary advice until the signs become unmistakable or intolerable - when the dog breaks his housetraining or begs to go outside during the night for example.
The typical Cushing's dog has a bulging, sagging belly caused by a decrease in muscle strength and redistribution of fat from body storage areas to the abdomen. As the disease progresses, hair loss may also become a major concern and the skin thins and may lose its resistance to infection.
Once suspected, Cushing's disease can be diagnosed by blood tests. Once it is diagnosed, tests can also differentiate between disease caused by pituitary gland tumor and disease caused by adrenal gland tumor.
About 85 percent of the cases are caused by pituitary tumors. Pituitary-induced Cushing's can be treated by drug therapy, but it cannot be cured. Adrenal gland tumors can often be surgically removed.
Treatment
There are several drug therapies available, including mitotane (Lysodren®), ketoconazole (Nizoral®), trilostane (Vetoryl®) and L-Deprenyl hydrochloride (Anipryl®, Eldepryl®, Carbex®, or selegiline). Each has potential side effects.
Lysodren is relatively inexpensive and convenient to use, but it carries the potential for serious side effects. Lysodren works by killing the outer layer of the adrenal gland that manufactures the corticosteroids. Careful regulation of the drug determines how much of the cortex is killed so that a normal amount of the hormone can be produced. This protocol requires periodic blood tests to make sure the dog has a normal amount of cortisol and does not develop Addison's disease or experience an Addison's crisis.* Once the proper amount of adrenal erosion has been achieved and the glands are producing the normal amount of cortin, the dog's condition may be maintained with doses once or twice a week..
Lysodren is given with food so it can be properly absorbed into the dog's body, so it is important that the dog have a good appetite.
Ketoconazole was originally developed to fight fungal infections in humans, but researchers discovered that it could be useful in fighting Cushing's by suppressing cortisol secretion in the adrenal glands. This drug cannot cause Addison's disease, but it requires indefinite daily dosing and is expensive. Some dogs cannot absorb it, rendering it useless in 20-25 percent of cases. It is useful for dogs that cannot tolerate Lysodren, has a low incidence of toxicity, and is completely reversible if necessary.
Anipryl® (L-Deprenyl) was approved for use in canine Cushing's disease in 1997. Originally studied as a treatment for Parkinson's disease in humans, L-Deprenyl helps restore the balance of natural brain chemicals, which in turn alleviate the symptoms of the disease. In clinical trials, about 70 percent of dogs responded favorably with a lessening of symptoms and a reduction in cortisol production.
Like ketoconazole, L-Deprenyl does not cause Addison's disease, and it has few side effects. However, it is more expensive than Lysodren and not as reliable or as quick to show results.
Trilostane (Vetoryl®) is the latest drug available to treat Cushing's disease. Approved for use in the US in 2009, it works by inhibiting an enzyme that is involved in the production of cortisol. Addison's disease is a possibility, so dogs taking this medication must be monitored with blood tests. Lethargy and appetite reduction are common side effects, especially early on.
Left untreated, Cushing's disease will progress and can lead to life-threatening disorders such as diabetes, congestive heart failure, and liver and kidney failure, and to chronic maladies such as hypothyroidism and infections of the skin, ears, gums, eyes, or bladder. If your pet exhibits any of the early signs of Cushing's and is six years old or older, make an appointment with your vet right away. Pituitary Cushing's disease cannot be cured, but the treatments available can prolong your pet's quality of life and keep him around for years longer. If an adrenal tumor is causing the disease, surgery may be indicated. Either way, it's better to get started on treatment.
For more information, go to "6 Treatment: Pituitary Cushing's Syndrome" by Wendy C. Brooks DVM, DABVP at http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=637 .
*Addison's disease is the opposite of Cushing's. Addison's results from too little cortisone, a situation that can occur if treatment causes erosion of too much adrenal tissue. The condition can be temporary or permanent and could be fatal if untreated. Signs of Addison's include vomiting, diarrhea, listlessness, and loss of appetite.
