Cushing’s Disease

Cushings Disease is a fairly common endocrine disease in dogs. The disease has been reported in cats, but is rare to virtually non-existent 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 in a specific region of its anatomy that controls regulation of the adrenal glands.  The reulting hyper-stimulatiion of the adrenal glands leads them 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 for everyday physiological function, 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, and chronic anxiety.

This disease is found in all canine breeds, but seems particularly more prevalent in the West Highland White Terrier. Cushing’s disease often goes unnoticed at first, and becomes apparent and or problematic as the disease progresses. The patient typically presents with all or some of the following clinical symptoms: drinking and urinating excessively (this sign is the most profound and consistent!), excessive weight gain, chronic skin infections and hair loss, pot belly appearance, behavioral changes.

The diagnosis of Cushing’s disease begins with routine blood work 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 health on the blood chemistry, the alkaline phosphatase (ALP) is significantly elevated, despite the other two being normal or close to normal. On urinalysis, the urine is often very diluted or poorly concentrated, 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 negative results. However, since no single blood test is perfect.  Disease can also be confirmed by the visualization of bilaterally symmetrically enlarged adrenal glands visualized on abdominal ultrasound.

In the past, treatment for Cushing’s disease was achieved by administration of a drug called Lysodren.   Lysodren works by causing destruction of adrenal gland tissue, effectively shrinking down the adrenal glands, with the result of the glands 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 begun 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.  The main benefit to Lysodren therapy for Cushings is the low cost associated with the drug.

Another more benign drug, called trilostane, has replaced Lysodren as the treatment of choice for canine Cushing’s Disease. Trilostane differs from Lysodren in two important aspects:

1.) It acts, not by destruction of adrenal gland tissue, but by inhibiting the enzymes involved with the production of cortisol.
2.) It is associated with significantly less toxicity, having a far less likelihood 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 it costs significantly more in comparison 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. Trilostane therefore is my first gold standard choice for treatment of Cushings Disease and will only consider dosing Lysodren in cases where trilostane is cost prohibitive for the owner.

Whether under treatment for Cushing’s Disease with trilostane or Lysodren, follow up monitoring is necessary, with the ACTH stimulation tests performed periodically. Once treatment 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 blood work and urinalysis should be performed at regular intervals to ensure systemic health.

Dogs with Cushings Disease with treatment have an average prognosis of 3 years. However, I believe this number has more to do with the fact that the majority of Cushings patients are diagnosed in the later years of life, and less to do with the Cushings itself. In less common cases where I diagnose it in younger animals, in my experience, average life expectancy is much longer than 3 years with treatment and vigilant monitoring. With the increasing popularity of trilostane as first line treatment, with its absence of side effects will likely serve to reflect a significant increase in the average life expectancy of Cushings Disease patients is it becomes a more mainstream treatment.

Roger L. Welton, DVM
Founder and Chief Editor, Web-DVM.net
President, Maybeck Animal Hospital

Article updated 11/9/2018