Cushing's Disease in Dogs

Cushing’s Disease is characterized by an overproduction of the hormone cortisol. This hormone, normally present in low levels and elevated during stress, helps to suppress inflammatory signaling and raise blood sugar, and is identical to the active ingredient in hydrocortisone anti-itch cream.

Cortisol production behaves like a thermostat, turning on and off in response to circulating levels of the hormone. It starts with the hypothalamus, a gland in the brain which releases the hormone CRH either in response to stress or to maintain the normal level of cortisol. CRH stimulates the pituitary gland to release ACTH, which is carried by the blood to the adrenal glands, located above the kidneys. The cortex (outer layer) of the adrenal glands secretes cortisol into the bloodstream. When a sufficient amount of cortisol has been released, the hypothalamus stops releasing CRH, which signals the pituitary gland to stop releasing ACTH, the lack of which causes the adrenal glands to cease the production of cortisol.

Cushing’s disease is a defect in this process leading to the production of excessive cortisol, which usually occurs either with the pituitary or adrenal glands. Excessive cortisol is harmful to health and can cause enlargement of the liver, hair loss, skin irritation (including bruising, acne and thinning of the skin), obesity and recurrent urinary infections due to a suppressed immune system. These symptoms present very gradually, but can shorten your pet’s lifespan and reduce their quality of life. See the veterinarian if your dog seems to be gaining weight without eating more, has any abdominal enlargement (potbelly), or is experiencing any hair loss. Since Cushing’s disease occurs more often in older dogs, it can be mistaken for simple aging. Only a veterinarian can tell you if your dog’s symptoms are age-related or indicative of a disease. Successful diagnosis and treatment can give you years longer with your pet.

• Excessive thirst and/or hunger
• Frequent urination
• Inability to cope with hot weather
• Lethargy or abnormal behavior
• Muscle weakness
• Redistribution of weight to abdomen (bony head and legs, fat body)
• Enlargement of the abdominal region
• Excessive panting when not hot or exercising
• Recurring urinary tract infections
• Hair loss
• Thinning or sensitization of the skin
• Acne or pustules
• Reddened, irritated or flaky skin

• Pituitary tumor or damage
• Adrenal tumor or damage
• Excessive treatment with corticosteroids.

Types

• Pituitary-dependent
• Adrenal-dependent
• Latrogenic (excessive steroid treatment)

Diagnosing Cushing’s disease can be difficult, as there is no single definitive lab test and many conditions may present along with the disease, complicating the diagnosis. A successful identification of Cushing’s will depend on the owner’s vigilance and description of changes in the dog’s habits and body, along with an analysis of all the symptoms by a veterinarian.

After a physical examination of your dog, checking for an enlarged liver and examining any skin complaints, the veterinarian will likely send urine and blood to the lab for testing. Abnormalities in the blood that may indicate Cushing’s include increased SAP (serum alkaline phosphatase), increased ALT, high cholesterol, high blood sugar, and lower BUN (blood urea nitrogen). Diabetes often co-presents with Cushing’s.

If your dog is otherwise healthy, a urine test measuring the ratio of cortisol to creatinine can easily indicate Cushing’s disease, but this test may also return positive results if your dog has additional, different conditions. This urine sample must be obtained by the owner at home when the dog is relaxed- the stress of a car journey or fear of the veterinarian's office can cause stress-released cortisol to artificially inflate the cortisol to creatinine ratio.

Once Cushing’s disease is suspected, there are a number of tests that can be performed to confirm the diagnosis and shed light on the source of the condition (i.e. pituitary vs adrenal problem). An ACTH stimulation test is conducted by administering artificial ACTH and measuring the response of the adrenal glands. Elevated response from the adrenal glands disproportionate to the amount of ACTH administered can indicate Cushing’s disease, and implicates the adrenal glands (or over-treatment with steroids) as the cause. An LDDS is less sensitive (often giving false positives if the dog has a different illness) but rarely gives false negatives. LDDS involves administering a pituitary-suppressing compound and measuring how long it takes the pituitary to “escape” the suppression and continue producing ACTH. A 3-4 hour window where ACTH production is low, followed by resumption of production at around 8 hours strongly suggests pituitary-dependent Cushing’s.

Once Cushing’s has been tentatively diagnosed, the next step is medical imaging to determine whether a tumor or unusual damage may be causing the problem. To examine the pituitary gland, MRI is the machine of choice. For the adrenal glands, ultrasound is preferred, and likely can be used in your veterinarian's office upon suspecting Cushing’s, as it is easily portable and noninvasive.

The treatments for Cushing’s disease usually fall under three categories: medication, surgery or radiation.For Pituitary-dependent Cushing’s, administration of mitotane helps to suppress production of ACTH. This treatment is usually administered for 7-10 days at a low dose to see how the animal responds. An additional ACTH response test should be conducted to check the dosage. The treatment is continued for life. It may be necessary to increase the dosage every so often, so an ACTH test and physical exam should be conducted every 3-4 months. For pituitary cancers or tumors, radiation therapy is often successful, but will require some temporary administration of mitotane to bring the ACTH levels under control initially. Additionally, trilostane can be used to reduce the adrenal gland’s ability to secrete cortisol, and is a reasonable alternative to mitotane in dogs who experience adverse reactions.

For Adrenal-dependent Cushing’s, surgical removal of adrenal tumors can bring the disease under control, but surgical staff must watch for a severe drop in cortisol due to the reduction in cortisol-producing tissue and the body’s acclimation to the higher levels. Corticosteroids may need to be administered to replace cortisone and gradually tapered off. Mitotane is not recommended for Adrenal-Dependant Cushing’s, as the necessary dose is 4 times as high, and carries much more serious side effects.

Finally, if Iatrogenic (treatment-initiated) Cushing’s is suspected, an examination of the steroids being used and the treatment is needed. Steroids are often administered to treat joint pain, arthritis, and autoimmune diseases, but are essentially just different types of cortisol, and can cause the same damage as a body’s natural overproduction of cortisol. Switching to a shorter acting, pill-form steroid like prednisone or prednisolone in addition to slow reduction of the dose can correct the disease.

The outlook for dog’s with Cushing’s will depend on the root cause of the disease, but is often positive. Pituitary tumors respond well to radiation therapy, and medication can bring the disease under control. Adrenal tumors are more serious and carry a more mixed outlook, with the overall cure rate after surgery being around 50%.

Mitotane treatment carries the risk of gastrointestinal irritation, weakness, and difficulty walking. This can be managed by dividing the treatment into two doses given with food morning and evening. Trilostane must be administered more often, and carries a slight risk of necrosis to the adrenal glands, so periodic ultrasounds should be conducted.

In the case of Iatrogenic Cushing’s, managing a dog’s arthritis or other inflammatory disorder with reduced steroids can be challenging, and settling for shorter walks and gentler play may be the tradeoff in treating Cushing’s. However, with a carefully planned dosage schedule and a faster-acting steroid, a successful balance can be struck to keep your pet healthy and mobile.