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Cushing's disease

Cushing's disease can trouble older dogs

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Animal bodies are a marvel of interactions between organs and systems kept in balance by the production of enzymes that aid in metabolic processes and hormones that regulate body functions. When the balance is disturbed by illness, injury, or advancing age, the body goes awry: appetite and water consumption may change, organs may malfunction, or medication to treat one illness may cause another.

Such is the case with Cushing's disease, also known as hyperadrenocorticism, the production of excess hormones from the adrenal glands. Cushing's disease usually strikes older dogs with a bucket-full of symptoms that can mimic other diseases. Increased appetite, increased drinking and urination, panting, high blood pressure, bulging abdomen, skin lumps and discoloring, hair loss, muscle weakness, and nervous system disorders can occur with the disease.

Located above the kidneys, the adrenals produce cortin, a complex of steroid hormones - including cortisone and cortisol - that help regulate body weight, mineral balance, the structure of connective tissue, some white blood cell production, and skin health. Adrenocorticotropic hormone (ACTH) from the pituitary gland stimulates the adrenal glands to produce cortin. Presence of a tumor on either the adrenal glands or pituitary can cause the adrenals to run amok and trigger Cushing's by producing an excess of cortin.

Diagnosis

The symptoms may creep up on the pet and pet owner. Pets do not appear to be critically ill because the danger signs of vomiting, diarrhea, pain, seizures, and bleeding do not occur. To the contrary, the symptoms often appear to be connected to normal aging. Muscle weakness also causes lethargy and a reduced tolerance for exercise, both of which are typical in aging dogs and cause no alarm in owners. Often owners do not seek veterinary advice until the signs become unmistakable or intolerable - when the dog breaks his housetraining or begs to go outside during the night for example.

The typical Cushing's dog has a bulging, sagging belly caused by a decrease in muscle strength and redistribution of fat from body storage areas to the abdomen. As the disease progresses, hair loss may also become a major concern and the skin thins and may lose its resistance to infection.

Once suspected, Cushing's disease can be diagnosed by blood tests. Once it is diagnosed, tests can also differentiate between disease caused by pituitary gland tumor and disease caused by adrenal gland tumor.

About 85 percent of the cases are caused by pituitary tumors. Pituitary-induced Cushing's can be treated by drug therapy, but it cannot be cured. Adrenal gland tumors can often be surgically removed.

Treatment

There are several drug therapies available, including mitotane (Lysodren®), ketoconazole (Nizoral®), trilostane (Vetoryl®) and L-Deprenyl hydrochloride (Anipryl®, Eldepryl®, Carbex®, or selegiline). Each has potential side effects.

Lysodren is relatively inexpensive and convenient to use, but it carries the potential for serious side effects. Lysodren works by killing the outer layer of the adrenal gland that manufactures the corticosteroids. Careful regulation of the drug determines how much of the cortex is killed so that a normal amount of the hormone can be produced. This protocol requires periodic blood tests to make sure the dog has a normal amount of cortisol and does not develop Addison's disease or experience an Addison's crisis.* Once the proper amount of adrenal erosion has been achieved and the glands are producing the normal amount of cortin, the dog's condition may be maintained with doses once or twice a week..

Lysodren is given with food so it can be properly absorbed into the dog's body, so it is important that the dog have a good appetite.

Ketoconazole was originally developed to fight fungal infections in humans, but researchers discovered that it could be useful in fighting Cushing's by suppressing cortisol secretion in the adrenal glands. This drug cannot cause Addison's disease, but it requires indefinite daily dosing and is expensive. Some dogs cannot absorb it, rendering it useless in 20-25 percent of cases. It is useful for dogs that cannot tolerate Lysodren, has a low incidence of toxicity, and is completely reversible if necessary.

Anipryl® (L-Deprenyl) was approved for use in canine Cushing's disease in 1997. Originally studied as a treatment for Parkinson's disease in humans, L-Deprenyl helps restore the balance of natural brain chemicals, which in turn alleviate the symptoms of the disease. In clinical trials, about 70 percent of dogs responded favorably with a lessening of symptoms and a reduction in cortisol production.

Like ketoconazole, L-Deprenyl does not cause Addison's disease, and it has few side effects. However, it is more expensive than Lysodren and not as reliable or as quick to show results.

Trilostane (Vetoryl®) is the latest drug available to treat Cushing's disease. Approved for use in the US in 2009, it works by inhibiting an enzyme that is involved in the production of cortisol. Addison's disease is a possibility, so dogs taking this medication must be monitored with blood tests. Lethargy and appetite reduction are common side effects, especially early on.

Left untreated, Cushing's disease will progress and can lead to life-threatening disorders such as diabetes, congestive heart failure, and liver and kidney failure, and to chronic maladies such as hypothyroidism and infections of the skin, ears, gums, eyes, or bladder. If your pet exhibits any of the early signs of Cushing's and is six years old or older, make an appointment with your vet right away. Pituitary Cushing's disease cannot be cured, but the treatments available can prolong your pet's quality of life and keep him around for years longer. If an adrenal tumor is causing the disease, surgery may be indicated. Either way, it's better to get started on treatment.

For more information, go to "6 Treatment: Pituitary Cushing's Syndrome" by Wendy C. Brooks DVM, DABVP at http://www.veterinarypartner.com/Content.plx?P=A&S=0&C=0&A=637 .

*Addison's disease is the opposite of Cushing's. Addison's results from too little cortisone, a situation that can occur if treatment causes erosion of too much adrenal tissue. The condition can be temporary or permanent and could be fatal if untreated. Signs of Addison's include vomiting, diarrhea, listlessness, and loss of appetite.

(Updated April 2011)

Norma Bennett Woolf

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