Canine Education: Cushing's Syndrome

What is Cushing’s syndrome? Cushing’s syndrome is a condition in which there is an excess of cortisol (cortisone). Cushing can be caused by drugs (e.g. prednisone, depo-medrol, dexamethasone, betamethasone) often prescribed for the treatment of many diseases; this syndrome is known as iatrogenic Cushing’s syndrome. It can also be caused by an excess of the body’s own cortisol, caused by a pituitary tumor or adrenal tumor. Below you will find more in-depth descriptions of the three known causes of Cushings.

· Latrogenic Cushing’s syndrome is caused by administration of drugs that suppress the body’s own cortisol production. Clinical signs and complications are similar to the naturally occuring disease. The dog can become dependent upon the drugs with chronic use, and abrupt withdrawal can lead to signs related to lack of cortisol, such as lethargy, depression, vomiting, and diarrhea. For these reasons, chronic steroid use is not recommended except in cases of life-threatening immune-mediated disease or chemotherapy protocols. The lowest possible dose of steroids should be used for therapy.

· Pituitary dependent Cushing’s disease is caused by a functional pituitary tumor that stimulates the adrenal glands to produce excess cortisol. The tumor is usually microscopic and benign. Sometimes the tumor can be large enough to cause pressure on the nerves to the eyes and the part of the brain called the hypothalamus, causing behavior changes, lack of appetite, and blindness, in addition to the other signs of Cushing’s syndrome. Pituitary-dependent Cushing’s disease makes up about 85% of spontaneous Cushing’s disease cases.

· Adrenal tumors can be benign, known as adenomas, or malignant, known as carcinomas. They produce cortisol independent of the normal regulatory mechanisms of the body. This is the cause of approx. 15% of occurrences of Cushings.

What are the symptoms or signs of Cushings?

Excessive drinking & urination
Increased appetite
Abdominal enlargement "potbelly" appearance
Weight gain
Decreased exercise tolerance/weakness
Lethargy
Panting
Symmetrical hair loss on the body
Slowed hair re-growth
Darkening of skin
Thin skin, bruising
Sterility/lack of cycling
Infections, skin and urinary tract

How can a Vet determine or diagnose Cushings? Routine blood work and urinalysis can help your vet diagnose this condition. They vet will look for Increases in specific liver enzymes, marked increase in serum alkaline phosphatase (SAP), which is induced by steroids, mildly increased ALT, GGT due to liver "swelling," also a white blood cell count. They’ll also want to check for elevated neutrophil count (the cells that fight infection) as well as decreased lymphocyte count (the cells that make antibodies) and decreased eosinophil count (the cells that cause allergies) and the creatinine ration of the urine.

Your vet may also recommend specialized tests, such as:

· ACTH stimulation test

· Low-dose dexamethasone suppression test (LDDST)

· High-dose dexamethasone suppression test (HDDST)

· Endogenous ACTH

· Abdominal ultrasound

· Abdominal radiographs (x rays)

· CT scan

Discuss these tests with your doctor, and decide which will be most effective, and which you can afford.

Can Cushings be effectively treated? Yes, in many cases, the condition can be treated effectively. Below we’ve outlined the treatments for the three known causes of Cushings.

Iatrogenic Cushing’s disease

Since iatrogenic Cushing’s disease is caused by giving steroids, often long-term, especially common in allergic dogs as "itch shots," withdrawal of the steroids is important in resolving the clinical signs. Sometimes, the body’s own production of cortisol is suppressed by the drugs, and slow tapering withdrawal of the drugs over weeks to months must be performed in order to allow the body time to recover its own production mechanisms.

Pituitary-dependent Cushing’s

Surgery to remove the abnormal pituitary has not been very effective in canines. However, it is commonly performed in humans. Because of the anatomy of the canine head removal of the entire pituitary gland can result in permanent hypothyroidism. Research is underway to investigating techniques to make surgery more successful in dogs.

Medical drug therapy is currently the treatment of choice in dogs. The most commonly used drug is Lysodren. This drug causes death of the adrenal cells that produce cortisol, eliminating the excessive production; this therapy must be continued for the life of the dog. The initial phase is induction, in which a daily dose is given; usually for 5-14 days to bring the cortisol levels down into the normal range quickly, eliminating the clinical signs of disease. The next phase is maintenance, in which the drug is given usually 1-2 times weekly to help keep the cortisol levels in the normal range. Signs that the dog’s disease is being controlled include a decrease in water consumption, urination, and appetite. Signs that an overdose has occurred include weakness, lethargy, lack of appetite, vomiting, diarrhea, and occasionally even death if left untreated (see Addison’s). Fortunately, these complications are rare; prompt attention and supportive care with steroids will eliminate the danger of these problems. Constant communication with your veterinarian is a MUST, as your vet will need to perform routine tests to insure the proper dosages.

Ketoconazole has also been used to treat Cushing’s disease. This anti-fungal agent blocks the formation of the steroid hormones. This is an expensive therapy however, and not all dogs will improve with this particular drug.

L-Deprenyl is the newest drug being used to treat pituitary-dependent Cushing’s disease. It works to block the monoamine oxidase type B enzyme, and enhances dopamine levels. Many owners report an increase in their pet’s activity levels and a decrease in excessive water consumption. This is also a daily, lifelong therapy, and is relatively expensive

Macroadenomas

Large pituitary tumors causing signs such as blindness, behavior change, and other neurologic signs are best treated with radiation therapy in order to shrink the tumor

Adrenal tumors

Surgery is the recommended treatment for adrenal tumors. Removal of a benign tumor, or even a small malignant tumor, often results in a cure.

Medical therapy for adrenal tumors can also be used in animals that are not good surgical candidates. Increased dosages and length of treatment are often necessary to control an adrenal tumor with Lysodren, and not all tumors will respond. There is also an increased risk of overdose and side effects with high-dose Lysodren therapy. Ketoconazole has been used with some success to manage these tumors. Again, you must consider the cost, as this would be a lifelong treatment for your dog as well, and requires your vet to perform tests frequently to insure proper dosages.

Once treated, what is the prognosis of a dog with Cushings? Dogs usually respond very well to therapy and are able to lead normal lives. Relapses are quite common with pituitary-dependent Cushing’s syndrome, and occur in about half of dogs with Cushings. This generally requires a change in the maintenance dose or re-induction therapy. Good owner observation and communication with the veterinarian are the most important factors that influence the success of treatment. Surgery will cure many benign adrenal tumors and small carcinomas. If there are no post-operative complications, there can be prolonged survival even with invasive tumors or with metastatic disease. Metastatic disease can be treated with medical therapy, often for greater than a year.

*This information is not meant to take the place of a Veterinarians advice. This is for educational and informational purposes only and is not meant as means for diagnosis.