Cushing's Syndrome in Dogs

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Cushing's syndrome or disease is a condition in dogs in which the adrenal glands become overactive, producing too much cortisol.

What Is Canine Cushing's Disease?

Also called hyperadrenocorticism, Cushing's syndrome occurs in dogs when the adrenal glands, which are responsible for producing cortisol, become overactive.

The adrenal glands are located near the kidneys, and their job is to produce several hormones including cortisol and regulate a number of body functions.

When the adrenal glands overwork, they produce too much cortisol. Normally, the adrenal glands release cortisol in response to stress, and the cortisol causes the body to be ready to fight or flee. Cortisol causes a dog's body to begin to burn fat and sugar and retain water. When too much cortisol is continually released, it has negative effects on body functions.

Signs of Cushing's Syndrome in Dogs

The signs of hyperadrenocorticism in dogs include:

• Increased water consumption
• Increased urination
• Pot-bellied appearance
• Increased appetite
• Weakness
• Hair loss, usually symmetrical bilaterally on the dog's trunk
• Thin skin
• Poor wound healing
• Recurrent skin infections
• Increased panting
• Calcinosis cutis, or firm bumps in the skin caused by calcium deposits

Signs of Cushing's syndrome in dogs usually come on slowly and aren't always obvious. Many times, they are written off as normal aging, since Cushing's is more common in older dogs.

Types of Cushing's Disease in Dogs

There are three ways that Cushing's syndrome can develop in dogs, and they have different treatments. They are:

• Pituitary-dependent Cushing's. Most dogs with Cushing's disease have this type. The pituitary gland in the brain develops a tumor which overproduces ACTH, the hormone that tells the adrenal glands to produce cortisol.
• Adrenal-dependent Cushing's. In this type of Cushing's, the dog's adrenal gland develops a tumor directly on it, which overproduces cortisol on its own. The pituitary gland drastically reduces or stops producing ACTH, and the opposite adrenal gland may stop working.
• Iatrogenic Cushing's. This occurs when a dog is given corticosteroid medications for a long period of time or at high doses. These medications are used for skin problems, arthritis, and many other conditions. When they are used at high doses and/or for long periods of time, they can cause the dog's pituitary gland to reduce or stop producing ACTH and the adrenal glands to stop producing cortisol. Stopping the medication suddenly can cause a life-threatening drop in cortisol, so medication is usually tapered off slowly to allow the dog's pituitary gland to begin to produce ACTH again.

Diagnosing Cushing's Syndrome in Dogs

Diagnosis of Cushing's disease in dogs can be complicated. Your veterinarian may find certain "flags" in baseline bloodwork that, together with physical exam and history findings, indicate that more specific testing should be done on adrenal gland function. These flags include:

• High cholesterol
• High alkaline phosphatase (alk phos) level
• Stress leukogram results on CBC
• Dilute urine

It's possible that the doctor will next recommend a urine cortisol/creatinine ratio (UCCR) test for your dog. This is another screening test and does not confirm Cushing's disease. However, if the test is negative, it does rule Cushing's disease out, so further, more expensive testing need not be performed. The test looks for high amounts of cortisol being removed from the body in the urine.

Specific tests for Cushing's disease include:

• Low dose dexamethasone suppression test (LDDST). Dexamethasone is a steroid that mimics the effects of cortisol in the body. When it is injected into a dog, the dog's pituitary gland should recognize it and stop producing ACTH for a short time. Therefore, during the LDDST test, a tiny amount of dexamethasone is given to the dog after a blood sample is taken to measure the baseline cortisol level. Cortisol levels are then checked at 4 and 8 hours after the dexamethasone injection. If the 8-hour cortisol sample is low, it indicates that the pituitary gland did its job. If there is no suppression of the cortisol levels, it means that the pituitary gland is overactive and the dog has Cushing's disease. This is the gold standard test for Cushing's disease in dogs.
• ACTH stimulation test (ACTH Stim). For this test, a dog's baseline cortisol level is measured and then he is given an injection of synthetic ACTH, and cortisol levels are measured two hours later. If the dog's cortisol level increases more than expected, Cushing's disease is probable. This test is more accurate for testing response to treatment for a dog with Cushing's syndrome than it is for diagnosing the condition.

Once Cushing's disease is diagnosed, an abdominal ultrasound may be done to attempt to differentiate a pituitary-dependent cause from an adrenal-dependent cause. If an ultrasound shows both adrenal glands are roughly the same size, smooth, and both enlarged, pituitary-dependent Cushing's is most likely. If one adrenal gland is significantly larger than the other and isn't smooth, adrenal-dependent Cushing's is most likely.

Treatment of Cushing's Disease in Dogs

The treatment for Cushing's disease in dogs usually depends on whether it is pituitary-dependent or adrenal-dependent.

Adrenal-dependent Cushing's disease may be treated by surgically removing the tumor. Further treatment may be necessary if the tumor is malignant.

Pituitary-dependent Cushing's disease is treated with medications. Lysodren and trilostane are the most common medications used.

• Lysodren works by destroying adrenal gland tissue. The pituitary tumor still secretes too much ACTH, but the adrenal gland can't overproduce cortisol anymore. However, too much adrenal gland may be destroyed, resulting in a dog with Addison's disease that will need lifelong treatment. During treatment with lysodren, the dog must be monitored closely for signs of low cortisol, which can be life-threatening. It's important to follow your veterinarian's instructions closely and be sure you know what signs to look for that indicate the cortisol has gotten too low and what to do.
• Trilostane works by interfering with an enzyme that is necessary for cortisol production. Though it does not work by destroying adrenal gland tissue, there have been cases where a dog's adrenal gland tissue did die, resulting in Addison's disease. It's not understood why this sometimes happens, but it is a possible concern, similar to when Lysodren is used.

Other medications for Cushing's disease are sometimes used when Lysodren or trilostane are deemed too risky or expensive. However, none are as reliable at treating Cushing's.

Dogs with iatrogenic Cushing's disease are treated by slowly withdrawing the external steroid that has caused the problem. These dogs must be watched closely, as well, to ensure that their cortisol doesn't get too low, which can result in collapse and death.

Some dogs with Cushing's disease are not treated. If they have a good quality of life and their illness does not produce signs that are particularly bothersome for the dog or owner, treatment may not be pursued due to the potentially life-threatening side effects of driving the cortisol too low.

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