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Cushings Disease
Cushings Disease is a fairly common endocrine disease in dogs. The disease has been reported in cats, but is rare to virtually non-existant in cats. Cushing's disease is caused by a benign tumor of the pituitary gland in the brain of dogs. While the tumor itself does not harm the brain or cause cancer, it acts as a larger pituitary gland, hyper-stimulating the adrenal glands to secrete excessive amounts of the hormone cortisol into systemic circulation. Cortisol is a "fight or flight" hormone, secreted when the animal is under stress. While it is a necessary hormone, in excess, it has the potential to lead to liver disease, cardiac disease, kidney disease, diabetes, urinary infections, skin infections, hair loss, obesity, breakdown of lean muscle mass, not to mention chronic anxiety.
This disease is found in all canine breeds, but seems particularly more prevalent in the West Highland White
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Terrier. Cushing's disease often goes unnoticed at first, and becomes apparent and or problematic as the disease The patient typically presents with all or some of the following clinical symptoms: drinking and urinating excessivley, excessive weight gain, chronic skin infections and hair loss, behavioral changes.
The diagnosis of Cushing's disease begins with routine bloodwork and urinalysis. Diagnostically, the first clue that a dog may have Cushing's disease, is that one of the three liver enzymes used to evaluate the liver on the blood chemistry, the alkaline phsphataase (ALP) is significantly elevated, despite the other two being normal. On urinalysis, the urine is often very diluted or unconcentrated, despite the blood chemistry indicating healthy kidneys.
With this initial evidence in hand, more specific blood tests can be run to confirm disease. Two such tests, the the ACTH stimulation test, and the Lose Dose Dexamethasone Test (LDDST) are the two most widely used tests for Cushing's disease. Both are acceptable, but I favor the LDDST, as it is associated with a lower percentage of false positive results. However, since no single .blood test is perfect, disease can also be confirmed by the visualization of bilaterally symmetrically enlarged adrenal glands on abdominal ultrrasound.
Traditionally, treatment for Cushing's disease was acheived by administration of a drug called Lysodren. Lysodren works by causing destruction of adrenal gland tissue, effectly shrinking down the adrenal glands, with the result of them producing less cortisol. However, since the pituitary glands will continue to over stimulate the
adrenal glands, they will enlarge once again if treatment is stopped. Therefore, treatment is for life, maintaining a homeostasis of adrenal destruction and regrowth.
Lysodren treatment is typically begnun in a loading phase, with daily administration for 7 - 10 days. Treatment is then cut back to 1-2 times weekly, depending on the apparent success on follow up diagnostics (more about this further down the page). Lysodren has the potential to cause toxicity, namely within the gastrointestinal system and at the level of the kidneys. Therefore, careful patient monitoring plays a large role in treatment.
Another, more benign drug, called trilostane, has become the treatment of choice for canine Cushing's Disease in Europe, and is quickly gaining popularity in the USA. Trilostane differs from Lysodren in two important aspects:
1.) It acts, not by destruction of adrenal gland tissue, but by inhibitting the enzymes involved with the production of cortisol.
2.) According to early data and anecdotal use of trilostane, due to the inherent properties of the drug, it tends to be associated with significantly less toxicity, having a far less likilihood of having deleterious effects on the patient's body, while proving itself quite effective in treating canine Cushing's disease.
The main drawback of the drug is that, currently, it is expensive, significantly so when compared to Lysodren. Also, rather than reaching a point where it can be administered one to two times weekly, trilostane has to be administered daily for life. Currently, I reserve trilostane for instances when Lysodren causes toxicity. I opt for Lysodren first, because the clients often have financial difficulty affording trilostane. In my limited experience in using trilostane, I have enjoyed success. Hopefully in the future, as trilostane gains wider use, it will become more affordable.
Whether under treatment for Cushing's Disease with trilostane or Lysodren, follow up monitoring is necessary, with the ACTH stimulation tests performed periodically. Once treratment is underway, the ACTH stimulation is the monitoring test of choice, as opposed to the LDDST for several important reasons. In addition to the ACTH stimulation test, routine bloodwork and urinalysis should be performed at regular intervals to ensure systemic health.
By: Roger L. Welton, DVM
Founder, Web-DVM
President Maybeck Animal Hospital
Author Canine and Feline 101
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