Cushing’s Disease in Dogs: Symptoms and Treatments

By: Laura McLain Madsen, DVM

Cushing’s disease in dogs, or canine hyperadrenocorticism, is a common endocrine disorder of middle-aged or senior dogs. The word “hyperadrenocorticism” refers to: hyper = overactive, adreno = adrenal gland, and cort = cortex, the outer layer of the adrenal gland.

What is Cushing’s disease?

Dogs (and people) have two adrenal glands, located just above the kidneys. The adrenals are involved in the “fight or flight” response, producing adrenaline. They also produce cortisol (similar to cortisone) which is a hormone that is involved in many basic body functions. The adrenal glands are under the control of the pituitary, a gland in the brain. So with Cushing’s disease in dogs, there is an overproduction of cortisol and other hormones.

What are the symptoms?

Cushing's Disease in Dogs - Excessive ThristSymptoms of Cushing’s disease in dogs include excessive thirst (polydipsia), excessive urination (polyuria), excessive appetite (polyphagia), hair loss, a “pot belly” appearance (because of weakness of the abdominal muscles), generalized muscle weakness, “blackheads” on the skin, skin infections, and urinary tract infections. Not every dog will show every symptom.

How much is too much?

Dogs vary quite a bit in how much water they drink. In general, drinking any amount up to 15 ounces per ten pounds of body weight in a 24-hour period is considered normal.

Increased urination includes both an increased volume (a larger puddle with each urination) and an increased frequency (urinating more often). Dogs might have accidents in the house because they can’t get outside in time.

Excessive thirst and excessive urination could also be caused by other disorders, particularly diabetes mellitus and kidney disease. Your vet will start with basic lab testing to rule out other problems.

What causes Cushing’s disease in dogs?

There are two types of Cushing’s disease in dogs. The first type is called pituitary-dependent hyperadrenocorticism (PDH). In PDH, there is a tumor of the pituitary gland in the brain which overproduces the hormone ACTH, which in turn “tells” the adrenal glands to overproduce cortisol. PDH is more common in small breed dogs (poodles, Boston terriers, Schnauzers).

The second type is an adrenal tumor (AT). In AT, there is a tumor of the adrenal gland which overproduces cortisol. AT is more common in large breed dogs. The tumor may be either benign or malignant. Malignant (cancerous) tumors can cause other problems due to invasion into other body structures.

How is Cushing’s disease diagnosed?

Typically, your veterinarian will run initial lab tests including a complete blood count (CBC, to look at the red and white blood cells), a serum chemistry panel (to assess liver and kidney function, blood sugar, electrolytes), and a urinalysis (to look for evidence of kidney disease or urinary tract infection). The initial testing won’t definitively diagnose Cushing’s disease in dogs but there are values which, if abnormal, are suggestive of hyperadrenocorticism. One liver enzyme called alkaline phosphatase (ALKP or ALP) is frequently quite elevated while other liver enzymes are only mildly elevated. The cholesterol and blood sugar may also be elevated. The urine is usually very dilute (watery) and bacteria might be seen.

Other initial tests that might be run include a blood pressure (many dogs with Cushing’s have hypertension) and a urine culture (to check for urinary tract infection).

If the initial lab work and symptoms are consistent with Cushing’s there are a variety of further diagnostic tests your veterinarian may recommend. Unfortunately, none of the tests is perfect, and results may sometimes be inconclusive, necessitating additional testing. Some of the tests are for diagnosing Cushing’s while others are for differentiating PDH from AT.

Specific tests include:

• Urine cortisol-to-creatinine ratio: This test measures the amount of cortisol in the urine. If the result is normal it rules out Cushing’s (meaning the dog definitely does not have the disease). However, an elevated result doesn’t necessarily mean the dog has Cushing’s; further tests are required.

• ACTH stimulation test: This test involves drawing a blood sample, administering an injection of a medication that stimulates the adrenal glands, and then drawing another sample one or two hours later. The levels of cortisol in the “before” and “after” samples are compared. Dogs with hyperadrenocorticism will have an overactive response.

• Low dose dexamethasone suppression test (LDDST): This test involves drawing a blood sample, administering an injection of a medication that suppresses (inhibits) the adrenal glands, and then drawing additional samples four to eight hours later. The levels of cortisol in the “before” and “after” samples are compared. Dogs with hyperadrenocorticism will have a poor response.

• High dose dexamethasone suppression test (HDDST): This is the same as the LDDST but uses a higher dose of medication. It can distinguish between AT and PDH.

• Endogenous ACTH: This blood test measures the level of ACTH being produced by the pituitary, which will be elevated in PDH and decreased in AT.

• Ultrasound: An ultrasound of the abdomen to look at the adrenals will usually distinguish PDH from AT. In PDH both adrenals will appear enlarged, while in AT generally the tumor will be visible on one adrenal gland while the other gland will be shrunken.

What is the treatment for Cushing's disease?

The treatment of Cushing’s disease in dogs depends on type, PDH or AT. Medications are used for PDH while either medications or surgery are used to treat AT. If symptoms of Cushing’s are only mild, many veterinarians actually recommend not treating because of potential side effects of the treatment. When—and if—the symptoms become more severe then treatment can be started. Once treatment is started it will generally need to be continued life-long.

Medications that are used to treat Cushing’s disease are:

Trilostane (Vetoryl®) is newly licensed in the United States for treatment of Cushing’s in dogs. The medication inhibits cortisol production by the adrenals and can be used for either PDH or AT. It is generally a safe medication but there are some side effects, usually mild (lethargy, decreased appetite, vomiting or diarrhea). In addition, there have been a few reports of sudden death associated with the drug. Dogs on trilostane will need to have periodic monitoring with the ACTH stimulation test.

Mitotane (Lysodren®, o,p’-DDD) is an older drug but is still used by many veterinarians. The drug is a relative of the pesticide DDT, and acts by killing off some of the adrenal gland to decrease cortisol production. Treatment consists of an induction phase (a high dose of drug given daily until symptoms diminish, usually 3-8 days) and then a maintenance phase (a low dose of drug given twice per week to prevent reoccurrence of symptoms). The dog needs to be monitored very carefully during the induction phase to prevent overdose. In a dog who previously had a voracious appetite, the induction phase ends on the first day the dog doesn’t wolf his food down. Dogs on mitotane will need to have periodic monitoring with the ACTH stimulation test.

Ketoconazole (Nizoral®) is actually an antifungal drug usually used to treat fungus infections, but as a side-effect it blocks production of cortisol. Ketoconazole is generally inexpensive and safe, so it is an option if the other medications can’t be used.

Selegiline (Anipryl®, L-deprenyl) affects dopamine, a neurotransmitter in the brain. It is licensed for treatment of canine cognitive dysfunction (“doggy senility”) and Cushing’s disease in dogs. Because it acts in the brain rather than the adrenal, it is only effective against PDH, not AT, and is only helpful in certain cases of PDH.

Surgery is frequently recommended as a treatment for an adrenal tumor. By removing the tumor, the symptoms related to overproduction of hormones by the tumor will abate. There are potential risks associated with surgery and anesthesia. Advanced imaging with ultrasound, MRI or CT is generally performed before surgery to assess whether the tumor has invaded other structures.

What is the long term prognosis?

The prognosis for dogs with Cushing’s is generally good. With treatment they can live a normal lifespan and continue their normal activities. The water intake, urination and appetite should return to normal. Dogs will need to be monitored periodically by a veterinarian.

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