Canine Cushing's Disease

 General Information

Hyperadrenalism is a slowly progressing disease and the early signs are often not noticed. These include increased appetite, increased drinking and urination, reduced activity and enlargement of the abdomen. As the disease progresses, these signs intensify, and the pet may become fat, pant heavily, and lose hair evenly over each side of the body. In some cases, hair loss may be the only apparent change. These clinical signs are the same as the side effects seen in dogs on steroids such as prednisone of dexamethasone.

Cushing’s Disease is a disorder of the adrenal glands in which excessive adrenal hormones are produced, mainly cortisol. The cause of hyperadrenocorticism (HAC) may be abnormal pituitary gland function (a glan in the brain), a tumor of the adrenal gland, “cortisone” (steroid) therapy, or other unexplained over-activity of the adrenal gland. Pituitary dependant HAC accounts for about 80% of all cases.

Extensive laboratory tests (both blood and urine) and radiographs or ultrasound may be needed to diagnose the condition, find its cause and plan treatment. Unfortunately the tests available today often come back as inconclusive making diagnosis very difficult. Several different tests or repeats of test may be necessary to come to an accurate diagnosis. Treatment of pituitary dependant HAC is more aimed at controlling clinical signs and making your pet more comfortable than actual treatment of the tumor. Adrenal gland tumors can sometimes be cured with surgery (some are to invasive to attempt to remove), but will also respond to medical management. Since treatment is aimed at controlling clinical signs and not at curing the problem, the disease will progress, but your pet will be much more comfortable than without treatment.

Induction of Treatment for Cushing’s Disease with mitotane.

Control, rather than cure, is the aim of treatment in most cases of HAC. Treatment with Mitotane must be carefully monitored, since the drug used in therapy may cause underproduction of adrenal hormones and a shock-like state known as an Addisonian crisis.

Treatment is inducted with a drug called Mitotane (Lysodren) You will be giving the medication twice a day for 7 to 10 days. Then an ACTH Stimulation test is run to determine the response to treatment. The kidneys and electrolytes may be checked at this time also. Dogs with adrenal HAC may not respond as well to medical treatment alone as dogs with pitutitary dependant HAC.

If your dog develops any of the following signs contact your veterinarian immediately:

• Drinking less than 2oz/kg of water a day- in dogs that were drinking excessive amounts (>3oz/kg/day) before treatment
• Vomiting or diarrhea
• Taking 15-30 minutes longer to eat than before start of mitotane therapy
• Listlessness, depression or weakness
• Skin condition worsens

If adequate control is not reached after the first ACTH Stimulation test then therapy will continue until a satisfactory ACTH Stimulation test is obtained. The test is run about every 7-10 days

The most-common side-effects of mitotane include lethargy, stomach upset, loss of appetite, vomiting and diarrhea. Although less common, hypoadrenalcorticism and an addisonian crisis also are potential side-effects. In rare instances, dogs may experience central nervous system (CNS) signs, ataxia, weakness and seizures.

Maintenance Therapy for Cushing’s Disease with mitotane.

1. Once adequate control is reached then your dog will need Mitotane twice a day once a week.
2. An ACTH Stimulation test will be run in 1 to 3 months after start of maintenance therapy and then every 3 to 6 months after that. It is common for clinical signs to recur during maintenance therapy due to the dose becoming inadequate. If you notice signs returning see your veterinarian so the dose can be adjusted accordingly.

Treatment with Trilostane (Vetoryl).

Trilostane (brand name Vetoryl) was approved for treatment of Cushing's disease in dogs in 2008. It works by blocking the excessive production of cortisol from the adrenal gland.

Treatment is started at a dose calculated based on your pet's weight. You will need to have your pet examined and have bloodwork performed in 2, 4 and 12 weeks to assess effectiveness of treatment and to adjust medication dosing. Then if your dog is stable he/she will need to be seen every 3 months unless something changes. Immediate signs that the treatment is effective include increased activity level, decreased appetite (no longer ravenous), decrease in thirst/drinking, and decreased urination.

Possible side effects include poor/reduced appetite, vomiting, lethargy/dullness, diarrhea, and weakness. Occasionally, more serious reactions, including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis or adrenal necrosis/rupture may occur, and may result in death.

Treatment with Anipryl (selegiline HCl).

There is an alternative to Mitotane called Selegiline HCl (Anipryl). The benefits of this treatment are no worry of an Addisonian crisis as it does not destroy part of the adrenal gland. The drawbacks are it is expensive, especially for larger dogs, and has a variable success rate. Treatment with Anipryl consists of a pill once a day for life and includes regular monitoring of the disease through bloodwork.

Prognosis and disease progression.

The average life expectancy for dogs with adrenal dependant HAC is 36 months. The average life expectancy for dogs with pituitary dependant HAC is approximately 30 months with younger dogs living longer (i.e. 4 years or more).

Many dogs ultimately die or are euthanized due to complications related to Cushing’s disease such as pituitary macrotumor syndrome, systemic hypertension, pulmonary thromboembolism, diabetes mellitus, infection, etc.

• Pituitary macrotumor syndrome is a result of the tumor on the pituitary gland expanding into other parts of the brain. The dog will begin showing neurologic signs such as aimless wandering, pacing, circling, and behavior alterations. These signs usually develop 6 months or more after diagnosis.
• Pulmonary thromboembolism is most commonly seen shortly after treatment. The presenting sign is sudden respiratory distress or difficulty breathing. Once this occurs the prognosis for recovery is grave. It usually requires 7 to 10 days on oxygen therapy if the animal survives.
• Development of diabetes mellitus is also another potential problem with Cushing’s disease. The high levels of steroids in the blood stream can cause insulin resistance. The signs of diabetes are very similar to the signs of Cushing’s disease so it is important to notify your doctor if you notice them returning. Many dogs can have their diabetes controlled for a time with regular insulin therapy.
• Infections are common in animals with Cushing’s disease due to the overproduction of steroids. Steroids suppress the immune system and therefore prevent the animal from fighting off infection. One of the goals of treatment is to lower the animal’s blood levels of steroids to prevent this from happening. Urinary tract infections and skin infections are most commonly seen. The more severe and life threatening ones include sepsis and pyelonephritis (kidney infection).