Dog Cushing's Disease

Introduction

Cushing's disease in dogs is synonymous with hyperadrenocorticism and is the most common endocrine disorder in aging domestic dogs. It gets its familiar name from Dr. Harvey Cushing, who first described the disease in humans with pituitary gland tumors. There are several forms of the syndrome commonly referred to as canine Cushing's disease: pituitary-based, adrenal-based and iatrogenic. All forms are chronic and slowly progressive. They cause the same clinical signs, and each requires treatment. The syndrome results from long-term exposure to abnormally high levels of steroid hormones.

Causes & Prevention

Causes of Cushing's Disease in Dogs
Cushing's disease is caused by an excess of freely circulating corticosteroid hormones, which are produced by the adrenal glands. The adrenal glands are tiny, paired structures located in the abdomen above each kidney. The outer layer of these glands, called the adrenal cortex, produces corticosteroid hormones, which in turn are responsible for regulating electrolyte concentration, managing inflammatory reactions and suppressing the immune system, among other things. Production and release of steroid hormones are regulated by the pituitary gland, which is located in the brain. The pituitary gland produces adrenocorticotropic hormone (ACTH), which when released stimulates production of steroids by the adrenal glands.

The accurate term for Cushing's disease is hyperadrenocorticism. It is most commonly caused by excess production and secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland, due to either functional pituitary tumors or excess release of corticotrophin-releasing factor (CRF) by the hypothalamus. Cushing's can also be caused by functional tumors of the adrenal gland, which promote excessive secretion of corticosteroids even without stimulation by pituitary ACTH. Finally, Cushing's can be caused by excessive or prolonged use of steroid medications that stimulate or simulate excessive adrenal hormone production. This is called iatrogenic Cushing's.

Prevention of Canine Cushing's Disease
Unfortunately, other than managing the medical use of corticosteroids, there is no way to prevent hyperadrenocorticism in dogs. Functional tumors of the pituitary and/or adrenal glands occur for unknown reasons, and until the cause of those tumors is discovered, prevention of Cushing's disease is not realistic.

Special Notes
Hyperadrenocorticism is a chronically progressive disease that can cause severe and eventually debilitating signs in domestic dogs. Fortunately, several medical protocols are available to help manage this disease.

Symptoms & Signs

Introduction
Because hyperadrenocorticism most often afflicts middle-aged to older dogs, the symptoms of the disease can fool owners who think that they are simply seeing the natural effects of aging in their canine companions. Cushing's disease is caused by an excess of circulating cortisol hormone, which can result from functional tumors of the adrenal and/or pituitary glands. The disorder can also be caused by drugs administered for other ailments that stimulate excessive adrenal hormone production; this type of Cushing's is called "iatrogenic." However, if diagnosed properly and promptly, Cushing's usually can be managed in a way that either eliminates it or mitigates its severity and greatly improves the dog's quality of life. Since Cushing's is largely treatable, and possibly curable, recognizing the clinical signs is critical to a pet's prognosis.

Symptoms of Cushing's Disease
Cushing's occurs most commonly in older animals and can mimic the so-called "normal" signs of aging. Owners of affected dogs may observe one or more of the following signs of the disease:

Increased thirst and water intake (polydispsia)
Increased urine output (polyuria)
Inappropriate elimination (urinating in the house or other unusual places)
Increased appetite and food intake (polyphasia; often ravenous)
Weight gain; obesity
Panting
Abdominal enlargement (pendulous, distended abdomen; pot-bellied appearance)
Skin bruising
Patchy, symmetrical hair loss (alopecia)
Dry, dull hair coat
Thin or fragile skin that tears easily
Exercise intolerance
Weakness
Lethargy
Muscle atrophy
Enlarged (hypertrophied) or atrophied external genitalia
Infertility
Lack of coordination (ataxia)
Circling
Aimless wandering
Pacing
Poor wound healing
Cortisol increases appetite and thirst, so owners may notice that they are filling their dog's food and water bowls much more often than usual, and in fact may report that their pet's appetite is ravenous. Likewise, they often report abnormal hair loss that is symmetrical on both sides of their dog's body, along with loss of muscle mass especially in the legs. Muscle atrophy and corresponding redistribution of weight often give dogs with this disease a "pot-bellied" look. They also commonly have poor wound healing. Dogs with hyperadrenocorticism are predisposed to developing other problems, including heart failure, diabetes mellitus, infections and high blood pressure. Typically, several of these signs appear at or around the same time. As the disease progresses, affected dogs' signs typically worsen and increase in number. However, because Cushing's is largely treatable, possibly curable and usually manageable, it is important for dog owners to become familiar with the signs of this disease.

Dogs at Increased Risk
Cushing's disease appears most frequently in small dogs weighing less than 45 pounds. It is commonly seen in dogs over 6 years of age, with only a slight predisposition for female dogs, although dogs as young as 1 year have been diagnosed. Beagles, Boxers, Dachshunds, German Shepherds, Labrador Retrievers, Poodles and some breeds of Terriers (especially Boston Terriers) seem to be overrepresented.

Diagnosis & Tests

Introduction
Because the symptoms of Cushing's disease in dogs often mimic those of other diseases, an accurate diagnosis involves quite a bit of detective work on the part of the veterinary team. Routine blood and urine tests will help to increase or decrease the index of suspicion of Cushing's, but other tests are necessary to make a conclusive diagnosis. Fortunately, the diagnosis of hyperadrenocorticism is not particularly difficult for a veterinarian to make.

How Cushing's Disease is Diagnosed
Any dog suspected of having hyperadrenocorticism will likely undergo a thorough physical examination and history, together with an initial database including a complete blood count (CBC), a serum biochemistry profile and a urinalysis, with or without a bacterial culture. Other fairly routine diagnostic tests include abdominal radiographs and/or ultrasound, and blood pressure assessment.

There are a number of more advanced laboratory tests available to help a veterinarian confirm a diagnosis of Cushing's disease. These include a urine cortisol:creatinine ratio analysis, a low-dose dexamethasone suppression blood test, a high-dose dexamethasone suppression blood test, an ACTH stimulation blood test, and/or an assessment of endogenous blood ACTH concentrations. Magnetic resonance imaging (MRI) and computed tomography scans (CT or CAT scans) are also available to aid in the diagnostic process, as they may help visualize tumors of the pituitary or adrenal glands.

One of the simplest of these tests is the urine cortisol:creatinine ratio test. Normally, the owner is asked to catch the first morning's urine at home and bring it to their veterinarian for measurement of cortisol and creatinine levels. Normal test results essentially rule out the diagnosis of Cushing's. However, abnormal test results (called "false positives") are common in up to 75% of dogs that do not have Cushing's disease, making further diagnostic tests necessary.

The high- and low-dose dexamethasone suppression tests and the ACTH stimulation test, done together or separately, can lead to a conclusive diagnosis of Cushing's disease. These tests involve first taking an initial blood sample, giving the dog an injection of either dexamethasone or ACTH, and then taking subsequent blood samples at appropriate intervals. All of the blood samples are sent to a laboratory for careful analysis. The dog's veterinarian is in the best position to decide which tests to perform in any given case.

Special Notes
While Cushing's can be frustrating for owners, it is usually possible to manage.

Treatment Options

Introduction
Hyperadrenocorticism, commonly called Cushing's disease or Cushing's syndrome, is a chronic and slowly progressive disease that can eventually become severely debilitating for affected domestic dogs. Most cases of canine Cushing's cannot be cured. However, there are several readily available medical treatments for dogs with Cushing's disease to temper the symptoms of the disease. The goal of treating Cushing's is to reduce or eliminate the symptoms of the condition and thereby provide the dog with the best possible quality of life for his or her remaining time.

Treatment Options
Most authorities agree that Cushing's should not be treated unless the dog is displaying clinical signs of disease. Once that happens, the treatment protocol will depend upon which of the three forms of the disease is present. Iatrogenic Cushing's disease is caused by excessive or prolonged administration of corticosteroid drugs. This form of Cushing's can be treated, and usually cured, by tapering and slowly weaning the animal off of these medications, if possible.

Naturally occurring Cushing's disease, which is caused by functional tumors on either the adrenal or pituitary glands, can only be treated through surgery or with life-long medication. Adrenal tumors normally require surgical removal, which is highly effective unless the tumors have metastasized. Unfortunately, few of the naturally occurring Cushing's cases are caused by adrenal tumors. The majority of dogs with Cushing's have tumors on their pituitary gland. At the present time, pituitary tumors are not normally removable surgically.

Medical treatments for Cushing's disease are available, although the protocols are complex. Certain drugs, including Mitotane (Lysodren), Ketoconazole, L-Deprenyl (Anipryl) and Trilostane (Vetoryl), have been used to treat Cushing's with varied success, by suppressing production of corticosteroids. Each of these drugs can carry serious adverse side effects, and most can be administered only under a veterinarian's strict supervision. Blood tests should be run periodically to ensure that any chemotherapy is not causing or contributing to other medical problems. Despite the risk of side effects, supervised medical treatment options can improve and prolong the quality of life for dogs affected by Cushing's disease. Radiation may also be an option in some cases.

Prognosis
The prognosis for dogs with Cushing's disease is variable. If an adrenal tumor is the underlying cause of the condition and can be successfully removed, the prognosis is quite good. However, if a pituitary tumor is involved and the only treatment is chemotherapy, the prognosis is guarded.