All About Canine Cushing's Disease

What is Cushing's disease?

Cushing’s disease, also known as hyperadrenocorticism or HAC, is a hormonal disorder that occurs when the adrenal glands (two small glands located in front of the kidneys) continuously produce excessive amounts of cortisol. Cortisol is a natural steroid that has many important functions, including regulating stress, fighting infections, and maintaining body weight. However, too much cortisol can negatively affect a dog’s body and create a variety of symptoms.

​What causes Cushing's disease?

There are a few different causes and types of Cushing’s disease. The most common type is pituitary-dependent Cushing’s (pituitary-dependent hyperadrenocorticism or PDH). PDH is caused by a tumor on the pituitary gland, found at the base of the brain. This type of tumor produces excessive amounts of adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce more cortisol than the body needs. Pituitary tumors are typically small and benign but capable of growing larger.

Around 15% of dogs with Cushing’s have the adrenal-dependent form (adrenal-dependent hyperadrenocorticism or ADH). ADH is caused by a cortisol-secreting tumor on one or both of the adrenal glands. In 50% of dogs with adrenal tumors, the tumor is benign. In the other 50%, the tumor is malignant.

Another type is iatrogenic Cushing’s disease. This can be caused by the long-term or excessive use of steroid medications, such as prednisone.  In these cases, slowly discontinuing the steroids will usually improve the dog’s symptoms. Medication changes should always be done under a veterinarian's supervision.

Rarer forms of Cushing’s disease are food-induced Cushing’s and atypical Cushing’s. For more details about these conditions, please see the Atypical Cushing's Disease and Food-Induced Cushing's Disease articles.

What signs of Cushing’s might a dog owner notice?

The most noticeable signs of Cushing’s disease include:

Increased thirst

You might notice that your dog seems to be thirsty all the time and needs to have his or her water bowl filled more often. 

Urinary issues

These can include increased urination, urinary incontinence, and/or frequent urinary tract infections. Your dog might start leaking urine or having accidents in the house.

Increased appetite

​A ravenous appetite is a common symptom. Your dog might constantly beg for food or steal from the trash.

Hair loss or slow-growing hair

Dogs that have hair loss from Cushing’s disease will usually lose it along the back, abdomen, and tail, while hair on the head and legs stays intact. Some dogs may have more subtle hair changes, such as a dull coat. 

Skin issues

Your dog’s skin may be thin and wrinkled. Some dogs also develop calcinosis cutis, a condition where calcium is deposited in the skin and causes raised, hard areas. 

Muscle weakness

You might notice weakness in your dog’s hind legs or difficulty standing, climbing, or jumping. This is because cortisol is a catabolic hormone, meaning it breaks down muscles.

Excessive panting

Your dog may pant excessively, even when resting. Cushing’s impairs the body’s ability to regulate temperature.

Pot-bellied appearance

Many dogs with Cushing’s have an abdomen that appears bloated. This is usually the result of weakened abdominal muscles and an enlarged liver, both of which are characteristic of excess cortisol.

What signs of Cushing’s can be seen in bloodwork or urine tests?

The following changes are commonly seen on blood and urine tests of dogs with Cushing’s disease:

Dilute urine

Urine is often very diluted, with a specific gravity less than 1.020.

Recurrent UTIs

About 50% of dogs have a urinary tract infection at the time they’re diagnosed with Cushing’s disease. However, because cortisol is anti-inflammatory and dilutes urine, the infection may not show up on urinalysis. A urine culture is often needed to confirm UTIs in dogs with Cushing’s disease.

Proteinuria​

Normally, urine contains very small amounts of protein. Protein loss into the urine can be a sign of Cushing’s disease and may persist even after treatment. 

Elevated cholesterol

Cholesterol and triglyceride levels may be higher than normal. 

Elevated alkaline phosphatase (ALP)

ALP is a liver enzyme that increases in response to cortisol. It’s not unusual for this value to be over 1,000 U/L in dogs with Cushing’s disease, but some dogs will only have a mild or moderate increase.

What tests are used to diagnose Cushing’s disease?

There are several tests that can help a veterinarian to diagnose Cushing’s disease, including:

Low Dose Dexamethasone Suppression Test (LDDST) 

This is considered the most accurate test to diagnose Cushing’s disease. The only cases where this test isn’t recommended are (1) when a dog has a significant non-adrenal illness, such as diabetes mellitus, or (2) when medical history suggests iatrogenic (steroid-induced) Cushing’s disease. In those cases, the ACTH stimulation test is a better option.

For the LDDST, dogs normally need to be at the veterinary clinic for a full 8 hours. On the day of the test, they’re given an injection of a synthetic cortisol called dexamethasone, and three blood samples are collected. The first blood sample is taken prior to the dexamethasone injection. The second and third samples are taken 4 and 8 hours following the injection. Once the test is complete, the amount of cortisol in the samples is measured.

In dogs without Cushing’s, dexamethasone will suppress cortisol levels for the entire 8 hours. In dogs with Cushing's, however, cortisol levels will be above the laboratory cutoff at 8 hours. This cutoff is typically around 1.5 ug/dL, though some labs use different reference ranges. For more insight into interpreting LDDST results, see this chart by IDEXX Laboratories.

NOTE: The LDDST is prone to false positives in dogs that are stressed, sick, and/or have non-adrenal illnesses, such as diabetes or hypothyroidism. If possible, other illnesses should be resolved or controlled before testing for Cushing's disease.

ACTH Stimulation Test (ACTH stim)

When screening for Cushing's, the ACTH stim is considered less accurate than the LDDST because of its high rate of false negatives. However, it does have a lower rate of false positives than the LDDST, which makes it beneficial in some cases. ACTH stim is particularly helpful in screening diabetic dogs for Cushing’s. This test is also used when iatrogenic Cushing’s disease is suspected.

For this test, a blood sample is drawn, and then the dog is given a dose of synthetic ACTH. ACTH is the hormone that stimulates cortisol release. An hour after the ACTH injection, another blood sample is drawn. When the test is completed, the cortisol levels in the blood samples are measured. Generally, a post-ACTH cortisol level above 22 µg/dL is consistent with untreated Cushing’s disease (unless a dog has iatrogenic Cushing’s, in which case the cortisol value will be low).

​NOTE: The ACTH stim test is also used to monitor dogs that are being treated with Vetoryl (trilostane) or Lysodren (mitotane). For more details, please see the All About Vetoryl and All About Lysodren articles.

Urine Cortisol/Creatinine Ratio (UCCR)

The UCCR is a simple test involving a urine sample. Ideally, this sample should be collected at home first thing in the morning, when urine is most concentrated. Your vet will evaluate the ratio of cortisol and creatinine in the urine. A normal ratio almost always rules out Cushing’s disease. On the other hand, because the UCCR test has a high false positive rate, an elevated ratio doesn’t necessarily confirm Cushing’s and should be followed up with another screening test.

How can I know whether my dog has adrenal and pituitary Cushing’s disease?

There are a variety of tests that can point to whether a dog has adrenal or pituitary-dependent Cushing’s disease. As this chart shows, a certain pattern of results on the low-dose dexamethasone suppression test can both diagnose Cushing’s disease and identify it as being pituitary dependent.

When results of the low-dose test are consistent with Cushing’s but ambiguous as to the type, further testing is needed. Next steps might include the High Dose Dexamethasone Suppression Test, Endogenous ACTH, or abdominal ultrasound. The way the adrenal glands look on an ultrasound can provide strong clues about the type of Cushing’s disease. In dogs with an adrenal tumor, it’s common for one adrenal gland to be enlarged, while the other gland is smaller than normal. In dogs with pituitary Cushing’s, both adrenal glands will be the same size and shape and most likely enlarged.

Further information on this topic can be found in our article, Determining Type: Adrenal or Pituitary Cushing’s.

How is Cushing’s disease treated?

Most dogs with Cushing’s disease are treated with a medication called Vetoryl (trilostane). Information about Vetoryl can be found in our All About Vetoryl article.

Can Cushing’s be cured?

​In most cases, Cushing’s disease is a lifelong condition. The only “cure” is removing the tumor that causes it. Pituitary tumors have been successfully removed through surgery or reduced in size by radiation, but these procedures are not widely available. If the disease is adrenal-dependent, surgically removing the adrenal tumor is usually possible. Unfortunately, however, adrenal surgery is a major operation that carries significant risks. It’s one of the most difficult procedures in veterinary medicine and should only be performed by a highly trained and experienced surgeon.

Can young dogs get Cushing's disease?

​Yes, contrary to popular belief, younger dogs can get it. Although Cushing's is more common in seniors, it is not a senior only condition. 

What are the potential complications of Cushing's disease?

​Cushing's disease can cause serious complications and illness, including diabetes mellitus, high blood pressure, kidney damage, and pancreatitis. Dogs with Cushing's also face increased risk of developing blood clots. The risk of all of these complications is higher when Cushing's disease isn't well controlled. With good care and monitoring, however, it's entirely possible for a dog with this condition to live a long, normal life.

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