Overview of Canine Hyperadrenocorticism Hyperadrenocorticism, commonly referred to as Cushing's disease or Cushing's syndrome, refers to a disease state in which an overactive adrenal tissue produces excessive amounts of cortisone. Cortisone and related substances are essential hormones of the body, but when produced in excessive amounts these substances may cause systemic illness.
A small tumor in the pituitary gland (located at the base of the brain) is the cause of Cushing's syndrome in 80 to 85 percent of dogs with hyperadrenocorticism. The tumor produces a hormone called adrenocorticotropic hormone or ACTH that stimulates the adrenal glands to grow larger (become hyperplastic) and produce excessive amounts of cortisone. This type of Cushing's syndrome is called pituitary-dependent hyperadrenocorticism because it originates from the pituitary gland.
In the remaining 15 to 20 percent of dogs with Cushing's syndrome, the cause is a tumor of the adrenal gland. This form is called adrenal-dependent hyperadrenocorticism because it originates from the adrenal gland itself.
Occasionally, a dog might have a diagnosis of iatrogenic Cushing's disease. This is not an adrenal disorder, but rather it is caused by the administration of steroids (given to treat other diseases) to a dog. Long-term administration of steroids can cause a dog to exhibit all the classic signs of Cushing's disease. In this case, the excessive steroids are not being produced in the body, they are being provided as a form of medication to your pet.
Canine Cushing's syndrome usually occurs in middle-aged to older dogs with most affected dogs being over 9 years of age at presentation. The syndrome does not have a strong gender bias, but it may occur slightly more often in female dogs than in males. Dogs of any breed can develop Cushing's syndrome, but it is most common in poodles, dachshunds, miniature schnauzers, and German shepherds. Boxers and Boston terriers are prone to development of Cushing's syndrome caused by pituitary tumors.
Hyperadrenocorticism can be difficult to recognize due to its variable clinical symptoms and very gradual onset. For example, many owners mistakenly assume that the changes they see in their dog are simply a result of the aging process.
What to Watch For with Cushing's Syndrome in Dogs
Abnormal high blood concentration of cortisone results in the clinical symptoms of Cushing's syndrome. These include:
Chronic skin or urinary tract infections, excessive panting, lethargy, muscle weakness, and calcium deposits in the skin (calcinosis cutis) are other symptoms of Cushing's syndrome.
Diagnosis of Hyperadrenocorticism in Dogs
No single laboratory test definitively identifies Cushing's syndrome, and the disorder should not be diagnosed solely on the basis of laboratory tests. Your veterinarian should also consider the medical history and physical examination findings when establishing a diagnosis and determining the appropriate laboratory tests to perform. Several of the following diagnostic tests may be required for the diagnosis of Cushing's syndrome:
Treatment of Hyperadrenocorticism (Cushing's Syndrome) in Dogs
Several approaches may be used to treat dogs with Cushing's syndrome. Treatment options depend primarily on whether the Cushing's syndrome is pituitary-dependent or adrenal-dependent.
Pituitary-dependent Hyperadrenocorticism in Dogs
Adrenal-dependent Hyperadrenocorticism in Dogs
Follow your veterinarian's instructions very closely when administrating medications, especially in the induction phase when using mitotane. Observe your dog for weakness, vomiting, diarrhea, loss of appetite or change in attitude. You should also observe your dog for improvement or worsening of clinical signs.
Follow-up with your veterinarian for routine re-evaluation of blood tests so as to maximize the chance for successful treatment.
There is no known way to prevent Cushing's syndrome. However, some preventative measures may lead to earlier diagnosis and potentially more effective treatment:
In-Depth Information on Canine Hyperadrenocorticism
The adrenal glands are small endocrine organs located near the kidneys. They are comprised of two major parts:
The adrenal cortex is further divided into three regions, each of which makes a different type of steroid hormone.
The adrenal medulla produces catecholamine hormones such as epinephrine that help the body respond to sudden emergencies.
Normally, control centers in the brain regulate the production of cortisone by the adrenal cortex. The hypothalamic region of the brain secretes a hormone called corticotrophin-releasing hormone (CRH), which in turn stimulates the pituitary gland to produce adrenocorticotropic hormone (ACTH). ACTH stimulates the production of cortisone by the adrenal cortex. High circulating concentrations of cortisone normally suppress ACTH production by the pituitary gland thus maintaining normal blood concentrations of cortisone by means of a “feed-back” mechanism. In dogs with Cushing's syndrome, abnormally high blood concentrations of cortisone occur as a result of a pituitary tumor that produces abnormally high concentrations of ACTH or by an adrenal tumor that produces abnormally high concentrations of cortisone. An understanding of the body's normal “feed-back” mechanism helps your veterinarian diagnose Cushing's syndrome and identify the underlying cause (pituitary tumor vs. adrenal tumor).
Diseases that Can Produce Similar Signs of Cushing's Disease
Several other diseases may produce symptoms similar to those of Cushing's syndrome. Such disorders include:
In-depth Diagnosis of Hyperadrenocorticism in Dogs
The diagnosis of Cushing's syndrome involves two steps.
A good medical history and complete physical examination are crucial to establishing a diagnosis. No single laboratory test conclusively establishes a diagnosis of Cushing's syndrome. The diagnosis must be made on the basis of the medical history, physical findings and results of carefully selected laboratory tests and diagnostic imaging procedures. Often, Cushing's syndrome is suspected on the basis of clinical findings, but the diagnosis remains elusive even after completion of appropriate diagnostic tests.
Diagnostic Tests may include:
A conclusive diagnosis of hyperadrenocorticism is based on measurement of blood cortisol concentration before and after stimulation with adrenocorticotropic hormone (ACTH stimulation test) or before and after suppression by intravenous administration of a potent cortisone-like drug called dexamethasone (dexamethasone suppression test). An exaggerated response to stimulation with ACTH and lack of suppression after dexamethasone administration are expected when blood cortisol concentrations are measured in dogs with Cushing's syndrome. Measuring a single blood cortisol concentration at rest is of little or no value because blood cortisol concentrations in normal dogs and those with Cushing's syndrome can vary greatly.
The ACTH stimulation test is also the best method of diagnosing Iatrogenic Cushing's disease. Dogs with the iatrogenic disease will actually have a decreased response to ACTH due to suppression of the production of endogenous (produced within the body) cortisol. This suppression of adrenal cortisol production is caused by the chronic administration of medications containing glucocorticoids.
Tests used to differentiate pituitary- and adrenal-dependent hyperadrenocorticism include:
Treatment of Pituitary-dependent Hyperadrenocorticism in Dogs
Usually, the first sign that blood cortisol concentration is normalizing is a decrease in appetite or decrease in water consumption. If these signs are noted, you should contact your veterinarian to schedule re-evaluation. The ACTH stimulation test is used to monitor blood cortisol concentrations after mitotane treatment. The time required to normalize blood cortisol concentration and complete the induction phase of treatment is five to nine days. The time required, however, varies considerably from dog to dog depending on many factors, including the severity of their hyperadrenocorticism. Some dogs require only two or three days for induction whereas others may require three weeks or more.
At any time during induction, if you feel that your dog is ill you should contact your veterinarian. If the induction phase continues too long, the dog's blood cortisol concentration and the responsiveness of its adrenal glands may fall below the minimal level required for health, and a condition called hypoadrenocorticism (Addison's disease) may develop, requiring immediate veterinary care. Prednisone (a synthetic cortisone-like drug) sometimes is prescribed for use in an emergency situation. The response to prednisone in a dog that has received too much mitotane during induction usually is dramatic. Some veterinarians advise giving small doses of prednisone routinely during the loading phase to minimize potential adverse effects. Other adverse effects of mitotane include vomiting, diarrhea, loss of appetite and lethargy. If the veterinarian and pet owner maintain close communication during the induction period, the induction phase usually proceeds smoothly and hyperadrenocorticism is controlled with few or no adverse effects.
The second phase of treatment is the maintenance phase. The maintenance phase is designed to keep your dog in remission by maintaining low normal blood concentrations of cortisol and keeping the adrenal glands under-responsive to ACTH.
Treatment of Adrenal-dependent Hyperadrenocorticism in Dogs
Optimal treatment for your dog requires a combination of home and professional veterinary care. Follow up can be crucial, especially if your dog does not improve. Administer as directed all medications prescribed by your veterinarian. Alert your veterinarian promptly if you are experiencing problems treating your dog.
Monitor for any recurrence of clinical signs, especially increased thirst, increased urination and increased appetite. If your dog suddenly deteriorates, especially during treatment with mitotane, contact your veterinarian immediately. He or she may prescribe prednisone to be given in the event of an emergency.
Routine blood testing (especially ACTH stimulation tests) will be needed at least twice a year.
Dogs on mitotane therapy generally require progressively higher maintenance dosages of the drug over time due to increasing blood cortisol concentrations.
Follow-up after surgical removal of an adrenal tumor includes monitoring the dog for recurrence by means of abdominal ultrasound examination.
Follow-up Care of Dogs with Cushing's Disease
Optimal care for the dog with Cushing's syndrome requires a good understanding of the disease and its symptoms, a significant financial and time commitment by the owner, and excellent communication between the veterinarian and the owner.