As dogs age, they are predisposed to more illnesses. One of the common findings in older dogs seen at the Animal Hospital at Thorndale is Cushing’s disease. Cushing’s Disease is a disorder in which the adrenal glands overproduce certain hormones. Another medical term disease for this disease is hyperadrenocorticism. There are two adrenal glands, one on each side of the abdomen; they are located just above each kidney.
The adrenal gland is divided into two layers: an outer cortex and inner medulla.
Medulla
The medulla produces hormones that help the dog respond to stress, regulate metabolism and maintain the tone of blood vessels. The most significant medullary hormone is adrenaline (epinephrine)
Cortex
The adrenal cortex is comprised of three layers, each of which has an important function. Some of these functions include the regulation of sodium and potassium balance and the production of steroid hormones. Some of these steroid hormones, such as glucocorticoids, are essential for sustaining life. The most well known glucocorticoid is cortisol (or cortisone).
Prevalence of Cushing’s Disease
Spontaneous Cushing’s disease is common in dogs over 6 years of age. The average age of onset is approximately ten years of age. Two forms of Cushing’s disease occur in dogs.
Pituitary-dependent Cushing’s (PDH), as described below, occurs at an increase incidence in the following breeds are breeds: Poodle breeds, German Shepherd dogs, Beagles, Labrador Retrievers, Dachshunds, Boxers, and some Terrier breeds, including Boston Terriers. It occurs in equal frequency in male and female dogs.
Adrenal-dependent Cushing’s (ADH), as described below, is more common in female dogs and in the larger breeds. The breeds which appear most often affected with ADH include Poodles, German Shepherd dogs, Dachshunds, Labrador Retrievers, and terriers.
Causes/Transmission
There are three mechanisms by which this disease can occur. Regardless of the cause, the clinical signs are essentially the same. It is important to identify the cause, however, because the various forms are treated differently and have different prognoses.
- Iatrogenic. Iatrogenic Cushing’s Disease means that the excess of cortisone has resulted from excessive administration of a cortisone-containing drug. This may occur from oral or injectable medications. Although the injections or tablets are given for a legitimate medical reason, excess can be detrimental. Prednisone, prednisolone, dexamethasone, and Depomedrol are commonly used corticosteroid medications.
- Pituitary gland tumor (PDH). The most common cause of Cushing’s Disease (80 – 85% of all cases) is a benign tumor of the pituitary gland in the brain; it is rare for these tumors to be malignant. The tumor causes the pituitary gland to overproduce a hormone (ACTH) that, in turn, stimulates the adrenal glands. Excessive cortisone secretion results. The tumor may be either microscopic (called a microadenoma) or quite large (called a macroadenoma). Depending on the size of the tumor, the presence of signs other than Cushing’s will be variable. It is hoped that if the activity of the adrenal gland can be controlled, the dog will live a relatively normal life. Unfortunately, this is not always the case. However, many dogs with this form of Cushing’s Disease can live normal lives for many years if they take their medication and stay under close medical supervision. Growth of the pituitary tumor would give the patient a less favorable prognosis.
- Adrenal gland tumor (ADH). In 15-20% of cases, Cushing’s Disease is the result of a benign or malignant tumor of the adrenal gland. If benign, surgical removal cures the disease. If malignant, surgery may help for a while, but the prognosis is less favorable than for a benign tumor.
Clinical Signs of Cushing’s Disease
The most commonly reported clinical signs associated with Cushing’s Disease are a tremendous increase in appetite, water consumption, and urination. Lethargy (lack of activity), panting, and muscular weakness are also seen in many cases. Problems related to the skin and hair coat include thin, easily bruised skin, loss of hair (alopecia), and excessive pigmentation.
Many of these dogs appear to have a bloated abdomen. There are two primary causes for this. The liver grows quite large with all types of Cushing’s; this enlargement is called hepatomegaly. At the same time, the muscles of the abdomen become weaker and are unable to adequately support the liver. With time, the dog develops a very pendulous-looking abdomen.
Occasionally, neurologic signs are seen. These signs include but are not limited to seizures, altered behavior, and incoordination.
Diagnosis of Cushing’s Disease
Diagnosis usually begins with a history of increased thirst, appetite, and need to urinate. A complete blood count and blood chemistry and a urinalysis are done to reveal clues that Cushing’s disease might be involved and rule out a number of other diseases (diabetes, kidney failure, etc.) Most dogs with Cushing’s disease will have an elevated serum Alkaline Phosphatase enzyme. While not in itself diagnostic of Cushing’s disease, this finding along with the behavior changes indicated further tests are needed. A number of tests are necessary to diagnose and confirm Cushing’s Disease. The most common initial test is a low-dose dexamethasone suppression test. This test may be followed by a high dose dexamethasone suppression test or an ACTH stimulation test. These tests are used to confirm that the dog has Cushing’s disease and establish a baseline for treatment monitoring. An abdominal ultrasound can also be very helpful in the diagnosis because adrenal size (s) may be affected.
How the tests work:
The low and high dose dexamethasone tests use the same principal. There is normally a “feedback loop” that regulates how much cortisol should be in the blood stream. An increase in blood cortisol is read by the pituitary gland at the base of the brain. In turn, the pituitary gland will decrease its own production of the hormone ACTH (adrenocorticotrophic hormone) which would normally act to stimulate the adrenals to produce more cortisone. Less ACTH means less stimulation to the adrenals, and the blood levels of cortisol drop back to normal. The low and high dose dexamethasone tests how well the feedback loop is working. Dexamethasone is an artificial cortisol that the pituitary gland recognizes as the real thing. By injecting dexamethasone into a normal dog, the dog’s own cortisol levels should go down. We measure the dog’s cortisol levels over an 8 hour period before and after a dexamethasone injection. Dog’s whose own cortisol levels go down and bounce back up or never go down during the eight hour period likely have Cushing’s syndrome. The low and high dose tests help distinguish between the pituitary (common) and adrenal (less common) forms of the disease.
The ACTH stimulation test works on the opposite principal. An injection of a specific amount of ACTH should stimulate a specific increase in the amount of cortisol the adrenals release. By measuring this response as normal, or overly exuberant, we can help diagnose Cushing’s disease. The ACTH stimulation test is also commonly used to monitor the dog’s response to medical treatment.
Treatment
Iatrogenic Cushing’s Disease. Treatment of this form requires discontinuation of the cortisone-containing medication. This must be done in a very controlled manner so that side-effects do not occur from withdrawal of the drug. When a prolonged course of cortisone therapy is necessary, the adrenal glands will atrophy and need time to “relearn” their normal functions. Unfortunately, stopping the cortisone can result in recurrence of the disease that was being treated by the cortisone. Because there may have been adverse effects on the adrenal glands, treatment is also needed to correct that problem.
Pituitary Tumor Treatment of PDH is designed to destroy the part of the adrenal cortex so that excessive cortisone will no longer be produced. Lysodren, is used to destroy the adrenal tissue. Lysodren is also known as mitotane or o’p’-ddd. If not enough drug is used, the abnormal tissue persists and the disease continues. If too much is used, most or all of the adrenal cortex will be destroyed, which can be life threatening. Therefore, careful monitoring of the dog is necessary in order to achieve good results. Because the pituitary gland is not being affected by the treatment, it continues to stimulate the adrenal gland. This means that continued treatment is necessary. Although a cure is not achieved, control is possible for many years if the tumor is small. If the tumor is large, local effects of the tumor invading surrounding tissues at the base of the brain can be the limiting factor in survival. Newer therapies have become available within the past two years. The drug, called Anipryl, does not offer the dramatic improvement more typically seen with Lysodren, but is safer. It is relatively expensive and is only useful for the pituitary-dependent form of Cushing’s. Trilostane is another drug being used to treat Cushing’s disease. As with Anipryl, the response is not always as good as with Lysodren. For owner’s who can carefully monitor their pet and who are willing to commit to the treatment schedule and keep the lines of communication open with their veterinarian, Lysodren can improve the quality of life for both dog and owner.
Treatment with Lysodren requires owners to very carefully monitor their dog’s thirst, appetite, and attitude. Any vomiting or diarrhea during the initial loading phase (usually lasting 3-7 days) should be reported to your veterinarian. We will perform an ACTH stimulation test prior to beginning the medication and again once the loading phase is over. We will give you detail instructions about what and how to monitor your dog so we can achieve optimum results safely. Once the adrenal cortisol production is properly reduced by the loading doses of Lysodren or Trilostane, as determined by the second ACTH stimulation test, we will give you specific directions on maintenance dosing tailored to your pet. Because there is a risk to too much suppression of the adrenal glands, we will also give you detailed instructions as to what to do if your dog has complications from the Lysodren or Trilostane . Each patient is unique and we work carefully with you and your pet to regulate and fine tune their cortisol production back to a more normal level. Follow up ACTH stimulation tests will be needed to be certain “fine control” is maintained.
Adrenal Tumor Treatment of an adrenal tumor requires treatment with Lysodren, Trilostane, and/or major surgery. With some adrenal tumors, especially the benign form (adenoma), good results can be achieved with drug therapy alone. In some cases, surgery is indicated for the purposes of obtaining a biopsy and/or attempting to remove the tumor mass. This surgery is potentially very dangerous to the dog, even when performed by skilled surgeons, because the tumor is typically surrounded by large blood vessels.
Prognosis
Dogs with the adrenal form of Cushing’s disease(ADH) caused by a benign tumor have a good prognosis whereas the prognosis is guarded with the malignant form (adrenal gland adenocarcinoma). Unfortunately, many adrenal tumors are malignant and often not amenable to surger. Fortunately, the adrenal form is much less common than the pituitary form. The prognosis with the Pituitary form of Cushing’s disease(PDH) is variable and depends upon the size of the tumor, the presence of concurrent medical problems, (microadenoma), and the willingness of the owner to continue with treatment and monitoring.