Cushing's Disease (Hyperadrenocorticism)

Written by Dana Brooks, DVM, Diplomate ACVIM

Cushing's disease is a condition in which the adrenal glands overproduce certain hormones. The medical term for this disease is hyperadrenocorticism.

The adrenal glands produce several vital substances which regulate a variety of body functions and are necessary to sustain life. The most widely known of these substances is cortisol, commonly known as cortisone. Decreased or excessive production of these substances, especially cortisol, may be life-threatening.

There are three mechanisms by which this disease can occur. Regardless of the cause, the clinical signs are essentially the same. It is important to identify the type of Cushing’s disease because the various forms are treated differently and each has a different prognosis. Cushing’s disease in older dogs is relatively common.  In cats it is rare, but extremely debilitating and difficult to treat.

Pituitary gland tumor. The most common cause of Cushing's disease (85% of all cases) is a tumor of the pituitary gland in the brain. The tumor may be either benign or malignant, but most are benign. The tumor causes the pituitary to overproduce the hormone ACTH that stimulates the adrenal glands to produce cortisol. The tumor may be microscopic or large. Depending on the size of the tumor, clinical signs other than Cushing's disease may be present, such as neurologic disorders. Generally, if the activity of the adrenal gland can be controlled, many dogs with this form of Cushing's disease can live normal lives for many years, as long as they take their medication and stay under close medical supervision. Growth of the pituitary tumor would give the patient a less favorable prognosis.

Adrenal gland tumor. Cushing's disease may be the result of a benign or malignant tumor of the adrenal gland.  If benign, surgical removal cures the disease. If malignant, surgery may help for a while, but the prognosis is less favorable than for a benign tumor because many have metastasized (spread to other organs) by the time they are found.

Iatrogenic. Iatrogenic Cushing's disease means that the excess of cortisol has resulted from excessive administration of a steroid medication. This may occur from oral, injectable, or rarely topical  medications.   Although the injections or tablets were usually given for a legitimate medical reason, their excess is now detrimental rather than beneficial.  Examples of these drugs include prednisone, prednisolone, dexamethasone, and triamcinolone.

The most common clinical signs associated with Cushing's disease are an increase in appetite, water consumption, and urination. Lethargy, or lack of activity, and a poor hair coat or hair loss are also common as are recurrent infections of the skin or urine.   If the animal is diabetic, Cushing’s disease can make the diabetes harder to control because it causes insulin resistance.  Many of these dogs develop a bloated or “pot-bellied” appearance to their abdomen due to an increase of fat within the abdominal organs and a stretching of the abdominal wall as the organs get heavier.  The pot-bellied appearance also develops because the muscles of the abdominal wall become weaker.   Panting and obesity - especially of the trunk are other signs. Cushing’s disease in cats is usually associated with uncontrolled diabetes mellitus or thin, easily torn skin.  The prognosis in cats is much more guarded than in dogs.

A number of tests may necessary to diagnose and confirm Cushing's disease. The two most common tests to detect Cushing’s disease are the ACTH Stimulation Test and the Low-Dose Dexamethasone Suppression (LDDS) test.  Abdominal ultrasound is useful to determine if there is an adrenal tumor or symmetrical enlargement of the adrenals which would be expected with pituitary dependent disease.  It may also help to identify concurrent problems such as bladder stones, changes in appearance of the liver or metastasis from an adrenal tumor.  A Urine cortisol: creatinine ratio is sometimes used as a screening test, and if negative, the chances of the dog having Cushing’s are low.  However, a positive result does not mean the dog has Cushing’s and other tests still need to be done.  Dogs with Cushing’s generally have dilute urine and elevated liver enzymes which may prompt your veterinarian to begin more specific testing to rule out an adrenal problem.

Treatment Options

Iatrogenic Disease

Treatment of this form requires a discontinuation of the steroid that is being given. This must be done in a controlled manner so that other complications do not occur. Unfortunately, it usually results in a recurrence of the disease that was being treated by the steroid and other drug therapy may be needed.

Adrenal Tumor

Treatment of an adrenal tumor requires surgical removal of the tumor.   Because of the proximity of the adrenal glands to major abdominal vessels  - the aorta and vena cava – this surgery is complicated and should only be performed by an experienced surgeon.  If successful, and the tumor is not malignant, there is a good chance that the dog will regain normal health.  If surgery is not an option, some of these patients can be adequately managed with medication, as discussed below.

Pituitary Tumor

Treatment of the pituitary-induced form of Cushing's disease requires long term medical therapy.  There are two drugs commonly used: Lysodren and trilostane.  Lysodren has been used to treat Cushing’s disease for many years, and it works by destroying the adrenal gland tissue. For this reason it is listed as a chemotherapy drug.  Lysodren is also known as mitotane or the chemical name o,p'-DDD.   If too little of the drug is used, the abnormal adrenal tissue persists and the disease continues.  If too much is used, most or all of the adrenal cortex will be destroyed, which can be life-threatening and result in reduced hormone production by the adrenal glands. This condition is known as Addison’s disease or hypoadrenocorticism, and can be treated with supplementation of the affected hormones. Careful monitoring of the patient is necessary in order to achieve good results. Because the pituitary is not being affected by the treatment, it continues to stimulate the adrenal gland. This means that lifelong treatment is necessary, and usually involves giving medication a few times per week.  Lysodren is usually not effective for treatment of Cushing’s disease in cats.

Trilostane is not currently approved for use in the United States, but it can be compounded, or obtained with special permission from Europe where it has been used for many years.  Trilostane works by inhibiting an enzyme which is responsible for conversion of an inactive version of several steroids into their active forms.   As soon as the medication is discontinued, the enzyme system begins working again and the dog’s clinical signs return.    Therefore, consistent administration of medication on a daily basis is necessary for good control.  Trilostane may be helpful for treatment of Cushing’s disease in cats if surgical removal of the glands is not an option.

Although a cure is not achieved with either treatment, control is possible for many years in most dogs. If the tumor is large, local effects of the tumor invading surrounding tissues in the brain can be the limiting factor in survival.  Cats have a poorer long term survival with Cushing’s disease than dogs.

Published on November 22, 2011.