Canine Cushing’s Disease

Of the handful of hormonal imbalances dogs develop, Cushing’s Disease is one of the most common. Also called hyperadrenocorticism, dogs with this disease have an overproduction (hyper) of cortisol (corticism) by their adrenal glands (adreno).

Cushing’s Disease occurs primarily in middle-aged and older dogs, and, while it can develop in any size or breed, smaller dogs are more commonly affected.

Normal cortisol production

The pituitary gland is a small pea-sized structure situated within the base of the brain. When the hypothalamus- also within the brain- sends the appropriate trigger, the pituitary gland releases a hormone called ACTH (adrenocorticotrophic hormone) into the bloodstream.

The role of ACTH is to tell the adrenal glands to manufacture and then release cortisol (aka, cortisone) into the bloodstream. Just as is true for us, dogs come equipped with two adrenal glands. They are small bean-shaped and bean-sized organs situated adjacent to each kidney.

Cortisol plays a role in a number of body functions. It’s responsible for normal appetite and an overall sense of well being. Additionally, the release of extra cortisol is vital during times of stress.

Three types of Cushing’s Disease

When Cushing’s Disease is suspected or has already been diagnosed, it is important that the veterinarian involved differentiates which form of Cushing’s Disease is at play. There are three possibilities:

Pituitary-dependent: This is the most common form of Cushing’s Disease, diagnosed in 85-90% of cases. The underlying cause is typically a small, benign growth within the dog’s pituitary gland. It is considered to be a “functional tumor” in that it produces an overabundance of ACTH. In response to this excess ACTH, both adrenal glands enlarge as they gear up to pump out excess cortisol.

Adrenal-dependent: This form of Cushing’s Disease is less common and occurs when a “functional tumor” develops in one of the adrenal glands. Without any influence from ACTH, this “rogue adrenal gland” produces excessive cortisol. The adrenal gland containing the tumor is enlarged. The other adrenal gland shrinks in size. For all practical purposes, it “takes a nap” because there is no longer need for it to manufacture cortisol. So fascinating how body parts work!

Iatrogenic: The term iatrogenic is an adjective meaning, “of or relating to illness caused by medical examination or treatment.” This form of Cushing’s Disease can occur in dogs receiving cortisone-containing medications.

Cortisone (often in the form of prednisone, prednisolone, or dexamethasone) is used to treat a variety of inflammatory, autoimmune, and cancerous conditions. It may be administered orally, via injection, or applied topically (skin medication, ear or eye drops). It’s not uncommon for dogs to develop Cushingoid symptoms in response to such therapy, particularly if it is administered long-term.

Symptoms

Cushing’s Disease can cause a huge long list of symptoms. Cushingoid dogs are extremely individualized in terms of which symptoms they manifest Some develop classic symptoms and look like the dog in the accompanying photo. Others are far more subtle in their presentation.

All of the symptoms below can occur in response to an elevated concentration of cortisol in the bloodstream.

  • Increased thirst
  • Increased urine output: Affected dogs may need to go outside to urinate multiple times during the night. The dog that has always been well-house trained is now having accidents in the house. Urinary incontinence (involuntary urine leakage) may result from over distention of the bladder.
  • Increased appetite: Some dogs become ravenous, begging for food or getting into the garbage for the very first time.
  • Pica: Eating strange things such as dirt, carpeting, etc.
  • Increased panting: The hallmark here is that the dog pants at inappropriate times with no apparent relationship to external temperature.
  • Hair coat changes: Thinning, baldness, change in texture
  • Recurrent skin infections
  • Recurrent ear infections
  • Recurrent bladder infections
  • Calcium deposits within the skin (calcinosis cutis)
  • Muscle wasting and weakness: This is most apparent in the hind legs and may result in less stamina on walks and difficulty jumping up or into the car or onto the couch. You’ve no doubt heard of anabolic steroids that increase muscle mass. Cortisol is a catabolic steroid- it causes muscle wasting.
  • Abdominal distention: Note that this is not caused by weight gain. Rather it is a result of weakness of the abdominal muscles

Less obvious abnormalities caused by Cushing’s Disease

In addition to the symptoms listed above, there are a few Cushing’s Disease-related abnormalities that are not readily apparent simply by observing the dog. Nonetheless, they are significant in terms of health consequences, and should be investigated and treated. In many cases, treatment of the Cushing’s Disease makes the following abnormalities go away:

  • Hypertension- high blood pressure
  • Proteinuria- excess protein in the urine
  • Poor diabetic regulation- Not uncommonly, diabetes and Cushing’s Disease develop hand-in-hand. Cushing’s Disease is suspected in diabetic dogs whose blood sugar levels have proven difficult to regulate with insulin. Cortisol is “gluconeogenic,” meaning that it ramps up sugar production in the body. So, it’s no wonder that Cushing’s Disease wreaks havoc on management of blood sugar levels in diabetic patients!

Diagnosis

Cushing’s Disease is initially suspected based on symptoms and/or characteristic abnormalities seen on routine screening blood tests. Measurement of the amount of cortisol within a urine sample increases suspicion.

A clear cut diagnosis of Cushing’s Disease is made via specific blood testing that measures the amount of cortisol in the dog’s blood stream. The results can help differentiate between the pituitary and adrenal forms of the disease (see above).  Dexamethasone suppression and ACTH response tests are the names of the blood tests most commonly performed to establish a diagnosis.

Once the diagnosis has been established, abdominal ultrasound is commonly recommended to further confirm which form of Cushing’s Disease is at play. In the case of pituitary-dependent Cushing’s Disease, both adrenal glands appear enlarged. With adrenal-dependent disease, the adrenal gland containing the tumor is enlarged, and the opposite adrenal gland is typically smaller than normal in size.

In cases of adrenal tumors, a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the abdomen may be recommended, particularly if surgical removal of the tumor is being considered. The scan identifies how aggressive (invasive) the tumor appears and helps predict the surgeon’s ability to safely remove it. The scan also screens for evidence of spread (metastasis) to other spots within the abdomen.

The iatrogenic form of Cushing’s disease is suspected based on symptoms and a history of cortisone therapy. The diagnosis is confirmed when withdrawal of the drug results in resolution of the symptoms.

Treatment

The goal of treatment of Cushing’s Disease is reduction of cortisol production back down to a normal range. This is tricky business as doing too much too quickly can result in a crisis caused by too little cortisol, a condition referred to as Addison’s Disease.

The best treatment for a dog with Cushing’s Disease depends most significantly on the following factors:

  1. The form of Cushing’s Disease that has been diagnosed
  2. Severity of the symptoms: If symptoms are mild and well tolerated (by the dog as well as the humans involved) and there are no significant abnormalities caused by the Cushing’s Disease (high blood pressure, protein in the urine, poorly controlled diabetes, etc.), taking a “wait and watch” approach is completely reasonable. In such cases, twice yearly recheck examinations are recommended to reevaluate the need for treatment.

Treatment of pituitary-dependent disease: Oral medication is the mainstay treatment for this form of Cushing’s Disease. There are a few medications to choose from- trilostane (Vetoryl) and mitotane (Lysodren) are the two drugs most commonly used. Both cause the adrenal glands to decrease cortisol production. It is imperative to perform blood testing- initially quite frequently- to evaluate the effect of the medication. Treatment is typically life-long.

Every dog is different in terms of how quickly their cortisol production decreases in response to the medication The key is to reduce cortisol production ever so gradually until just the right level is achieved. If treatment overshoots the mark, the result can be a whole host of symptoms (Addisonian crisis) brought about by too little cortisol in the blood stream.

Treatment of adrenal-dependent disease: Surgical removal of the adrenal tumor is the ideal therapy. This may not be possible because of the dog’s overall condition or the invasiveness or spread of the adrenal tumor. If surgery is not an option, medical treatment (trilostane or mitotane) is usually recommended.

Treatment of iatrogenic disease: The ideal treatment is gradual withdrawal of the cortisone-containing product the dog has been receiving. Abrupt withdrawal can result in an Addisonian crisis caused by too little cortisone in the bloodstream.

Prognosis

Many dogs with Cushing’s Disease are successfully treated and go on to achieve a normal lifespan. The prognosis is somewhat dependent on the type of Cushing’s Disease diagnosed. Most importantly, the prognosis depends on the finesse with which treatment is managed. Treatment can be tricky business- the more experience the veterinarian has with this disease, the greater the likelihood of a successful outcome. For this reason, it is wise to consider getting help from a veterinarian who specializes in internal medicine. Such a specialist will have likely managed dozens if not hundreds of dogs with Cushing’s Disease.

Questions for your veterinarian

  1. How do we know that my dog has Cushing’s Disease?
  2. What form of Cushing’s Disease has been diagnosed?
  3. Does my dog have high blood pressure?
  4. Does my dog have excess protein in the urine?
  5. What are the treatment options?
  6. Is treatment necessary at this time?
  7. How many patients with Cushing’s Disease do you typically treat during the course of a year?
  8. Can you recommend veterinary internist who can be involved my dog’s care?

Best wishes,

Nancy Kay, DVM

Diplomate, American College of Veterinary Internal Medicine
Author of Speaking for Spot: Be the Advocate Your Dog Needs to Live a Happy, Healthy, Longer Life
Author of Your Dog’s Best Health: A Dozen Reasonable Things to Expect From Your Vet
Recipient, Leo K. Bustad Companion Animal Veterinarian of the Year Award
Recipient, American Animal Hospital Association Animal Welfare and Humane Ethics Award
Recipient, Dog Writers Association of America Award for Best Blog
Recipient, Eukanuba Canine Health Award
Recipient, AKC Club Publication Excellence Award
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Please visit http://www.speakingforspot.com to read excerpts from Speaking for Spot and Your Dog’s Best Health.   There you will also find “Advocacy Aids”- helpful health forms you can download and use for your own dog, and a collection of published articles on advocating for your pet’s health. Speaking for Spot and Your Dog’s Best Health are available at www.speakingforspot.com, Amazon.com, local bookstores, and your favorite online book seller.

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5 Comments on “Canine Cushing’s Disease

  1. I was under the impression that dogs with Cushing’s can develop aggression. Is this true, and if so, how often do you see this symptom?

  2. I had an older (12 years old) Sheltie who died of this disease back when Trilostane was not yet available here in the US. I believe that the treatment we had then, Lysodren, caused the kidney damage of which she ultimately died. I sincerely hope never to have to deal with this disease again. It was a heart-breaker.

  3. Hi Judy,

    Thanks for your comments and questions. I happen to disagree with your veterinarian- I don’t believe that a dog with diabetes insipidus is at increased risk for developing Cushing’s Disease. While they both involve the pituitary gland, one is caused by a tumor that manufactures excess hormone and the other is caused by a depletion of hormone producing cells. Treatment of the pituitary version of Cushing’s Disease with radiation therapy or surgery could result in diabetes insipidus. Such treatments are not typically performed on dogs. Hope this helps.

    Warm best wishes,

    Dr. Nancy

  4. My 13.5-y.o. Lab has diabetes insipidus, and responds well to Desmopressin. My vet told me that the same hormonal abnormality that causes the DI puts him at elevated risk for Cushing’s, so I greatly appreciate your explanation of the different forms of the disease. Is it predictable which form of Cushing’s he would be most at risk for?

  5. We just lost our 14 yo Doxie to Cushings in March. He died within two years of diagnosis. He was on Trisolane compounded at a specific strength determined by ACTH testing. The Vet raised it a couple times and we thought the dose was right. However, Sammy just seemed to go downhill quickly. He became very weak. Then in the last couple weeks he seemed to be in considerable pain so we made the decision. I am not sure the Trisolane was the right decision for Sammy. I am not sure it improved his quality of life or even extended it. We could not afford heroic care and at 14 we did not feel we should. If I had it to do over, I would forgo the Trisolane at least as long as possible. All the peeing and drinking did not bother us at all. Also there are many ways to deal with incontinence like diapers, special beds and more. I appreciate you pointing out that wait and see is not a bad thing. If I deal with this again, I will be much slower to medicate if at all especially in a older dog. Sometimes we cannot extend their life no matter how much we want to. Thanks for this information.