Learn about the signs, symptoms and a new cutting-edge treatment for this devastating condition.
Cushing’s disease is a serious and life-threatening illness that affects an estimated 100,000 dogs annually in the United States. The disease can also predispose dogs to other health issues, including pancreatitis, diabetes and infections. Also known as hyperadrenocorticism, Cushing’s disease is a hormonal imbalance related to the function of a dog’s pituitary or adrenal glands. It’s usually associated with middle-aged or older dogs.
Out of sync
In healthy dogs, the pituitary and adrenal glands work in conjunction to produce a balance of hormones. The pituitary gland, which is located in the brain, produces adrenocorticotrophic hormone (ACTH). When released into the bloodstream, ACTH stimulates the adrenal glands (tiny, paired structures located in the abdomen above each kidney) to produce glucocorticoid (cortisol) hormones. Cortisol regulates how the body responds to stress. It also impacts a variety of bodily functions, including blood sugar levels, kidney function and immune response.
The output of cortisol from the adrenal glands is controlled by the pituitary gland through the production of ACTH. When the cortisol levels reach a certain point, the pituitary stops secreting ACTH. In contrast, when cortisol levels dip too low, the pituitary secretes additional ACTH.
When either the pituitary gland or the adrenal glands malfunction, a dog will develop abnormally high and sustained levels of hormones, which can lead to Cushing’s disease. Canine Cushing’s disease appears in three forms.
With pituitary-dependent Cushing’s, a tumor growing on the pituitary stimulates the gland to secrete excess ACTH. In response, the adrenal glands overproduce cortisol. Pituitary-dependent hyperadrenocorticism accounts for approximately 85 percent of Cushing’s disease in dogs.
“As a rule, pituitary tumors are benign, meaning they won’t spread outside the primary site,” says David Bruyette, D.V.M., Dipl. ACVIM, medical director of VCA West Los Angeles Hospital. “But because the brain is encased in bone, as the tumor continues to grow, it causes neurological side effects and can contribute to a dog’s mortality.”
The second cause of Cushing’s disease is adrenal based. It’s triggered by a tumor located on the adrenal gland and accounts for approximately 15 percent of cases. The tumor disrupts the communication between the adrenal glands and the pituitary gland causing overproduction of cortisol. “Half of adrenal tumors are malignant,” Bruyette says. “Even if we’re successful removing the tumor and initially getting control of the Cushing’s, there is a high chance that the disease will come back.” Even if owners don’t observe the return of Cushing’s signs in their dog, the cancer itself usually spreads.
Iatrogenic hyperadrenocorticism, the third type of Cushing’s syndrome, occurs when a dog receives long-term therapy with drugs that contain glucocorticoids for treatment of chronic conditions, such as allergies. Glucocorticoids reduce inflammation and suppress the immune system. Although the adrenal and the pituitary will attempt to respond by cutting ACTH and cortisol secretion, clinical signs of Cushing’s will occur if a dog continues to receive excess amounts of glucocorticoids.
“A lot of owners attribute the symptoms of Cushing’s disease to old age and will not bring them to the attention of their veterinarian,” Bruyette says. “But a dog that is slowing down, drinking more water, gaining weight and losing hair, is not normal.”
If Cushing’s is suspected, Bruyette recommends a complete physical and regular laboratory work to rule out any other concurrent diseases.
A series of blood tests will confirm whether a dog is Cushingoid. A baseline blood sample is typically drawn in the morning. The dog is then injected with a low dose of dexamethasone, which is a synthetic form of the glucocorticoid class of steroid drugs. Eight hours later, a second blood sample is taken. In a normal dog, the dexamethasone suppresses the cortisol levels. With Cushing’s, this effect does not occur. “Once Cushing’s is diagnosed, specific endocrine tests and ultrasounds can determine which form of the disease is present,” Bruyette says.
Several options exist for treating Cushing’s disease. Because of their location in the brain, pituitary-gland tumors are risky to remove. Traditionally, the disease is managed through medications that suppress cortisol production. Anipryl (selegilene), one of the more commonly used drugs, works in the brain by preventing the production of dopamine, which inhibits the overproduction of ACTH by the pituitary. This therapy relieves symptoms, but does not provide a cure. It also requires careful monitoring to ensure that cortisol levels don’t get too low.
For adrenal-based hyperadrenocorticism, the tumors can be surgically removed in some cases. “Chemotherapy and radiation are also options for treating adrenal tumors if a dog is not a surgical candidate,” Bruyette says. “Although these methods help prolong survival, they are not curative.”
Vetoryl (trilostane) and Lysodren (mitotane) are two medications that can be used to treat adrenal- and pituitary-based Cushing’s. “These drugs inhibit the adrenal glands from making steroids or they actually kill the adrenal so it can’t produce steroids,” Bruyette says.
In iatrogenic Cushing’s, the symptoms can be reversed if the causative drug is eliminated or tapered. To prevent this occurrence, veterinarians prescribe tapering doses or every-other-day doses of steroids.
An imaging device designed for human surgery is now being used to perform pituitary surgery in dogs. Bruyette and Tina Owen, D.V.M., Dipl. ACVS, a surgeon at VCA West Los Angeles Animal Hospital learned that Adam Mamelak, M.D., a neurosurgeon and co-director of the Pituitary Center at Cedars-Sinai Medical Center in Los Angeles, had developed a new surgical scope called a VITOM. The veterinarians expressed interest in adopting the device for canine neurosurgery.
Because of the length of a dog’s muzzle, surgeons have limited visibility when performing pituitary surgery, which requires cutting a small hole in the back of a dog’s mouth to allow entry into the skull at the base of the brain. The VITOM magnifies the operating field by up to 12 times and projects the image onto a high-definition video monitor. This increased magnification provides the surgeon with a sharper view of the tumor and surrounding brain structures, making removal safer and easier.
“Right now we’re focusing on animals that have large tumors because they have limited options for treatment,” Bruyette says. “Our goal is to eventually offer this surgery for all cases, regardless of the size of the tumor.”
In 2009, Howard Tarlow of Encino, Calif., noticed that Maggie, his 8-year-old Beagle, was drinking excessive amounts of water and urinating uncontrollably around the house. When Maggie tested positive for Cushing’s, Tarlow agreed to enroll her in a clinic trial using the VITOM.
“The recovery period for this surgery was rather extensive and Maggie required a lot of follow-up care,” Tarlow says. “But a few months after the procedure, she kept getting better and better. At some point, Maggie went back to being puppy-like. Two years later, she has more energy and more life.”
To date, 20 surgeries have been performed using the VITOM – 16 dogs and 4 cats. “There is a less than 5 percent intra-operative mortality rate [chance of the animal dying during surgery], and an 80 to 85 percent chance of remission,” Bruyette says. “We have dogs approaching two years since their initial surgeries. We routinely test them to determine if the tumor is growing back.”
Currently, VCA West Los Angeles Animal Hospital is the only facility in the United States performing this procedure. Bruyette estimates there will be five to 10 more locations throughout the country that will offer the treatment. The cost of the VITOM surgery and hospitalization, which usually lasts five to seven days, is estimated to be $8,000. “The cost is typically what a course of radiation therapy would be,” Bruyette says.
With each operation, tumor tissues, are collected and sent to Cedars-Sinai laboratories for testing. Using the tissue samples, researchers hope to develop drug therapies that will shrink the pituitary tumors. “We want to come up with novel drugs that get rid of both the tumor and the Cushing’s,” Bruyette says. “Although we don’t have data, we suspect the VITOM will greatly improve the life of a dog with Cushing’s because it will become symptom free.”
Signs of Cushing’s
Hyperadrenocorticism can manifest itself through a multitude of symptoms. Dogs might display just one or many of them, including:
- Increased water consumption
- Uncontrollable urination
- Increased appetite
- Panting and overheating
- Abdominal enlargement
- Calcified lumps in the skin
- Hair loss
- Thin, wrinkled or fragile skin
- Weight gain
- Weight loss