Cushing's disease, or hyperadrenocorticism, is a complex disease that results from chronic overproduction of hormones from the adrenal glands. The adrenal glands are two small glands that lay just ahead of your dog’s kidneys. In a normal dog, a complex system of interacting hormones control the production of other hormones. The regulatory gland is the pituitary gland. This gland produces a hormone called ACTH, which stimulates the adrenal glands to produce hormones, specifically cortisol, which is necessary for the function of many systems in the body. If something goes wrong in the pituitary gland or the adrenal glands and too much cortisol is produced, then Cushing's disease develops.
Cushing's disease is considered a disease of middle age and older dogs (6-7 years or older). Cats as well as dogs can develop Cushing's disease, however it is much more common in dogs. There is equal distribution between males and females. It is most commonly seen in poodles, dachshunds, terriers, German shepherds, and golden retrievers, however any breed is susceptible.
Increased appetite (polyphagia) leading to weight gain and obesity
Increased/excessive water consumption (polydipsia)
Increased/excessive urination (polyuria)
Urinary accidents in previously housetrained dogs
Excess panting, seeking cool surfaces to rest on
"Pot bellied" appearance caused by a weakening in abdominal muscle strength, redistribution of fat from body storage areas to the abdomen, and an enlarged liver
Bony, muscle wasted appearance of head
Hair loss (alopecia) especially noted on both sides of the body in the flank region, but can progress to all over hair loss
Hard calcified lumps in the skin (Calcinosis cutis)
Exercise intolerance, lethargy, general or hind-leg muscle weakness
Susceptibility to infections (especially in the skin and urine)
Cushing's Disease has Two Forms
There are two different distinct forms of Cushing's disease. There is pituitary dependent hyperadrenocorticism (PDH) and there is an adrenal-based hyperadrenocorticism (ADH).
Pituitary dependent hyperadrenocorticism involves the oversecretion of ACTH by the pituitary gland. ACTH is a hormone that stimulates the adrenal gland to produce glucocorticoids, specifically cortisol. In this form of the disease, the pituitary gland is most likely overproducing ACTH because of a pituitary tumor. PDH is responsible for around 80% of the cases of canine Cushing's disease. Pituitary-induced Cushing's can be treated with drug therapy, but it cannot be cured. In this form, both adrenal glands are enlarged on ultrasound examination.
Adrenal-based hyperadrenocorticism is usually a result of an adrenal tumor that causes an oversecretion of glucocorticoids, specifically cortisol. Adrenal tumors are responsible for around 20% of the cases of Cushing's disease. Adrenal gland tumors can often be surgically removed. Although there are two adrenal glands, these tumors generally develop in one gland and will lead to one abnormally large adrenal gland and one abnormally small gland on ultrasound examination.
There is also a third transient form of the disease called "iatrogenic" Cushing's disease that occurs as a result of an the animal being given high doses of steroids for an extended period of time. In this form of the disease, the symptoms of Cushing's disease will go away once the steroids are discontinued. The excess steroid in the body signals the adrenal glands to decrease their normal production of cortisol, leading to a decrease in the size of the adrenal glands on ultrasound examination.
Cushing's disease can present with a variety of symptoms and may also be involved with several different disease processes. Therefore, any dog suspected of having Cushing's disease should have a complete blood count (CBC), blood chemistry panel, and urinalysis performed as a routine part of the evaluation. There are several different tests that can be performed to get a definitive diagnosis of Cushing's disease. Many times more than one test must be performed to help confirm the diagnosis or to determine which form of the disease is present.
Urine Cortisol:Creatinine Ratio
In this test, the owner generally collects a urine sample at home (where the animal is not stressed). The sample is sent to a special laboratory for testing. Most dogs with Cushing's disease have an abnormal result, however, there are other diseases that can cause similar abnormal results. If this test result is abnormal, further diagnostic testing should be performed. If this test result is normal, Cushing's disease is very unlikely.
Low Dose Dexamethasone Suppression Test
The low dose dexamethasone suppression test is useful in diagnosing Cushing's disease in dogs. When given low doses of intravenous dexamethasone, normal dogs show a marked decrease in blood cortisol levels when tested 8 hours later. Most dogs (more than 90%) with Cushing's disease do not have a decrease in cortisol level after being given dexamethasone.
Abdominal ultrasound is helpful in three respects. First, it is a good test to evaluate all of the abdominal organs in the dog. Secondly, it is used to study the size and shape of the adrenal glands. The adrenal glands in pituitary dependent hyperadrenocorticism are usually normal in size or enlarged equally. If an adrenal tumor is present however, one adrenal gland is often abnormally large or uneven in shape. Finally, if an adrenal tumor is suspected, ultrasound can help identify any metastasis or spread to other organs.
Treatment consists of medical vs. surgical options. If an adrenal tumor is identified, then surgical removal is a viable option, however medical treatment can also be used. If a pituitary tumor is identified, no surgical options are readily available and medical management is necessary. There are currently several different medications available for the treatment of Cushing's disease. Below are descriptions of the two most common medical treatments.
Lysodren is an oral medication that is convenient to use, is relatively inexpensive and is probably the most widely used treatment. The downside of this drug is that it can have some serious side effects and regular blood-monitoring needs to be performed. Lysodren works by destroying the cells of the adrenal gland that produce the corticosteroid hormones. Careful regulation of the drug determines how much of the adrenal cortex is killed so that a normal amount of the hormone can be produced. The protocol requires periodic blood tests to make sure the dog has a normal amount of cortisol and does not develop a deficiency. Once the proper dosage has been determined, the dog's condition may be maintained by periodic treatment instead of daily doses.
Until recently, Lysodren was the only treatment available for pituitary dependent Cushing's disease. Trilostane is a newer treatment that is used to treat some dogs with Cushing's disease. It is more expensive, but may be used as an alternative treatment for dogs without some of the side effects caused by Lysodren. Trilostane interferes with production of cortisol in the adrenal glands without destroying the cells in the adrenal cortex. As with Lysodren, the dog must be re-examined repeatedly during the initial phase of treatment, and blood tests must be performed. In many cases, after several months of therapy the dose needs to be increased.
There are other drugs available to treat Cushing's disease, however their usefullness has not been determined.
The prognosis for this disease varies depending on the type of Cushing's disease present. Pets with Cushing's disease are predisposed to other diseases, such as diabetes mellitus, urinary tract infections, kidney disease, hypertension (high blood pressure), and pancreatitis. Pituitary Cushing's disease cannot be cured, but the treatments available can prolong your pet's quality of life and keep them around for years longer.
If your dog is exhibiting signs of Cushing's disease please call 516-621-4010 to schedule an appointment for an evaluation today.