Cushing’s disease (hyperadrenocorticism)

Cushing’s disease (also called ‘hyperadrenocorticism’ by veterinarians) is rare in cats. Although it is a severe disease it causes subtle changes in the early stages and many owners do not recognize the signs. Instead, the changes caused by the disease may be confused with aging.

Cushing’s disease is caused by prolonged exposure of the body’s tissues to high levels of the hormone, cortisol. It is called Cushing’s disease because it was named after a famous neurosurgeon, Harvey Cushing who first recognized it. It is also sometimes called “hyperadrenocorticism” or “hypercortisolemia“.

Cushing’s disease is caused by an excess of the steroid hormone, cortisol. In a normal animal, cortisol is produced by the adrenal glands, (which are located just in front of the kidneys). Scientists think that cortisol has hundreds of possible effects on the body. Among its other vital tasks, cortisol helps to:

• Maintain blood pressure.
• Slow the immune system’s inflammatory response.
• Balance the effects of insulin in breaking down sugar for energy.
• Regulate the use of proteins, carbohydrates and fats in the body.

Cortisol production is regulated by other hormones that are produced in the brain (from the pituitary gland). The hormones produced in the brain stimulate the adrenal glands to produce more cortisol. Because cortisol is so vital to health, the amount of cortisol produced by the adrenal glands is precisely balanced. In the normal animal cortisol is produced mainly at times of stress – in Cushing’s disease the levels of cortisol in the blood are always too high.

Cushing’s disease can occur following long-term treatment with corticosteroid drugs (so called iatrogenic Cushing’s) or as a naturally occurring disease. The majority of naturally occurring cases of Cushing’s disease are caused by a tumor in the pituitary gland. Although this is, strictly speaking, a brain tumor, the tumor is usually tiny and benign and causes no effects related to pressure in the brain. A smaller proportion of naturally occurring Cushing’s disease cases are caused by a tumor in the adrenal gland.

Therefore, the two forms of natural Cushing’s disease are:

• Pituitary-dependent Cushing’s disease (approximately 85% of cases): a tumor in the pituitary gland produces too much adrenocorticotropic hormone (ACTH) resulting in enlargement of both adrenal glands.
• Adrenal-dependent Cushing’s disease (approximately 15% of cases): a tumor of the adrenal gland makes one gland grow bigger and this gland produces more cortisol.

The signs of Cushing’s disease are extremely variable and can be subtle in the early stages. Cushing’s disease usually affects older pets (average age is 10 years but cats as young as 4 have been diagnosed with this condition). Because the changes come on slowly it is sometimes easier to spot them if you do not see an animal every day. Often it will be your veterinarian who examines your pet during its annual or semi-annual examination and points out that changes have occurred since your last visit. Many owners do not recognize the signs of Cushing’s disease in their pet, instead confusing the changes caused by the disease with signs of aging.

Steroid hormones affect almost every tissue in the body and the signs of Cushing’s disease can be diverse. One of the most common problems associated with Cushing’s disease in the cat is diabetes mellitus. In fact, most cases of Cushing’s in the cat are recognized because they are being treated for diabetes. The most obvious signs of diabetes are increased thirst and weight loss despite a good (or even increased) appetite. If your cat is drinking more or losing weight you should always take them to your veterinarian for a check-up. Typically, the diabetes seen in cats with Cushing’s is very resistant to insulin so high doses are needed to control the disease. Affected cats are also often reported to be lethargic and lacking energy. A small proportion of cats with Cushing’s are not diabetic although they may still show signs of increased thirst and increased urination.

Enlargement of the abdomen (a pot-bellied appearance) is common and Cushing’s disease can cause changes to the skin and haircoat. The skin may become fragile and thin, lose hair, bruise easily and heal poorly. Minor trauma (grooming or handling) may result in skin tearing and wounds. Often affected cats have a poor haircoat. The tips of the ears may start to curl over.

High levels of steroid hormone in the blood suppress the immune system and healing process; so, animals with Cushing’s disease may have repeated infections or wounds that do not heal as quickly as expected.

Iatrogenic Cushing’s is usually straightforward to diagnose as there is usually a history of long-term corticosteroid administration. However, cases of naturally occurring Cushing’s disease can be very difficult to confirm. Your veterinarian may suspect the disease based on simple blood tests, but specific blood tests are needed to confirm the diagnosis. These special tests measure the level of cortisol in the blood. However, because the levels of this hormone vary from hour to hour in a normal animal, the disease cannot be diagnosed on the basis of one blood test. Your veterinarian will need to take a number of blood samples before and after injection of hormones that affect the amount of cortisol produced by your cat. Some of these blood samples have to be handled very carefully and will need to be sent away to veterinary laboratories for analysis.

Adrenal gland size can be measured using ultrasound – this is a specialized technique that requires advanced equipment and technical skill so your cat may need to be referred to a specialist center for this procedure. If a tumor is present in the adrenal gland this should be visible on ultrasound (and one adrenal gland will appear larger than the other). If the disease is caused by a tumor in the brain, then both adrenal glands will be larger than normal.

X-rays may also be needed to show other potential problems caused by the disease. Examination of a urine sample can be useful in a cat with Cushing’s disease – high levels of cortisol in the blood can cause diabetes mellitus and your veterinarian will want to check for sugar in the urine to rule this out.

Treatment of iatrogenic Cushing’s is relatively straightforward with gradual reduction in corticosteroid administration required. Corticosteroids are potent drugs, and it is essential that they are not stopped suddenly. In some cases, successful treatment of iatrogenic Cushing’s can take several months. Treatment of naturally occurring Cushing’s disease in the cat is difficult and not without risk. Surgical removal of the abnormal adrenal gland (adrenalectomy) is the treatment of choice for adrenal Cushing’s disease. This is high risk surgery as affected cats are prone to infections and poor wound healing; there are high risks of bleeding at surgery as the adrenals are close to major blood vessels and cats with Cushing’s are more vulnerable to forming blood clots (thrombi) which can have serious consequences.

Pituitary cases are even harder to treat as there is no single perfect treatment. Medical treatment can be problematic in these cats most of the treatments that have been tried have had poor success, side-effects can be seen, and the drugs used are often not licensed veterinary treatments. Radiation therapy has been tried by some clinicians but is not widely available. Surgical removal of the pituitary, the treatment of choice in people with pituitary tumors, is a very high-risk surgery that is not often performed in cats. For these reasons, surgical removal of both of the adrenal glands may be recommended to prevent further cortisol production. This surgery is difficult and should be performed by a specialist in veterinary surgery, but in some cases medical treatment is given before surgery to stabilize the cat. In addition to the risks of surgery itself, it is very important that animals are closely monitored immediately after surgery, and they may need to spend time in an intensive care facility.

Most animals with Cushing’s disease are middle-aged or elderly and owners sometimes ask if it is worth treating them. The outcome for cats with Cushing’s disease with treatment is not good. Even with successful treatment fewer than half of all cats will live for more than a year after diagnosis. Unfortunately, if a cat had diabetes before treatment for Cushing’s disease, there is only a 50% chance that the diabetes will resolve with treatment. Some cats will need to be given insulin to control diabetes for the rest of their lives. Without treatment complications can be significant and will seriously affect the quality of your pet’s life.