Hyperadrenocorticism, also known as Cushing's syndrome, is an uncommon disease that develops when there is a chronic excess of the hormone, cortisol, circulating in the bloodstream.

What causes hyperadrenocorticism?

Long-term administration of corticosteroid drugs or naturally occurring disease can lead to an overproduction of cortisol. Cortisol is produced in the body by the adrenal glands; two small glands situated near the kidneys. Excess cortisol production by the adrenal glands can be caused by an adrenal tumour, or by a pituitary gland (a small gland at the base of the brain) tumour. Pituitary gland tumours produce another hormone, called adrenocorticotrophic hormone (ACTH), which stimulates the adrenal glands to produce excessive amounts of cortisol.

When Cushing's syndrome is caused by an adrenal tumour it is termed adrenal dependent Cushing's (or adrenal dependent hyperadrenocorticism), and similarly when it is caused by a pituitary gland tumour, it is termed pituitary dependent Cushing's (or pituitary dependent hyperadrenocorticism).

In approximately half of cases caused by adrenal gland tumours, the tumour is malignant (carcinoma), and in half of cases it is benign (adenoma). The majority of pituitary tumours causing the disease are benign very tiny tumours (usually 3-4 mm in diameter), but occasionally larger tumours and malignant tumours can occur.

How common is Cushing's syndrome in cats?

Cushing's syndrome is uncommon — by 2002 fewer than 100 cats with the syndrome had been reported in the veterinary literature. All the causes of Cushing's syndrome in cats are uncommon, much less common than the disease is in dogs. However, owners should always be advised of the signs to look out for if their cat is receiving chronic corticosteroid treatment. With the naturally occurring form of the disease, pituitary gland tumours are much more likely to be the cause than adrenal gland tumours.

Are particular breeds or ages of cats predisposed?

Cushing's syndrome occurs in middle-aged and older cats. A variety of breeds have been affected including Siamese, Persian, Abyssinian and domestic longhairs (longhaired moggies), but the majority of cats that have been affected are domestic shorthairs (shorthaired moggies).

What signs might my cat show?

Many different signs of Cushing's syndrome can occur, including excessive drinking and urination (polyuria/polydipsia), increased appetite, enlargement of the abdomen, lethargy, muscle wasting, poor coat condition/hair loss, curling of the ear tips and the development of very thin and fragile skin. The skin can be so fragile that it very easily bruises and also can very easily tear.

The majority of cats with Cushing's syndrome also have diabetes mellitus because cortisol interferes with the effects of insulin. Because of this interference, the diabetes is difficult to control even when insulin is administered by injection. One of the most common reasons for suspecting Cushing's syndrome in a cat is the development of diabetes that is very difficult to control, despite administering high doses of insulin. In this situation the most commonly seen signs are those associated with the diabetes (increased drinking and urination, increased appetite, weight loss).

How is the disease diagnosed?

Diagnosis of Cushing's syndrome is not always straightforward and usually requires multiple blood tests, urine tests and diagnostic imaging.

The first blood tests that would usually be performed are routine haematology and biochemistry. Doing these basic tests first rules out other more common diseases, for example, kidney disease and hyperthyroidism. Analysis of the urine may also be helpful in assessing kidney function, diabetes mellitus and also to look for bacterial infection in the bladder, as this is a common complication of both Cushing's syndrome and diabetes mellitus.

Diagnosis of Cushing's syndrome caused by long-term corticosteroid administration is usually based on the knowledge of this treatment being given and the development of typical clinical signs and blood abnormalities. However, the naturally occurring form of the disease is more difficult to diagnose and other urine tests and more specialised blood tests (ACTH stimulation, dexamethasone suppression tests) will be required. These blood tests require multiple blood samples to be taken throughout the day, so your cat would need to be hospitalised for a day or two in order for these tests to be performed.

Once Cushing's syndrome has been diagnosed, further blood tests and also imaging (X-rays, ultrasound and sometimes a CT or MRI scan) may be required to determine whether the disease is being caused by an adrenal tumour or pituitary tumour, before the best treatment option can be determined.

How is the disease treated?

If the disease has been caused by long-term administration of corticosteroids, then these drugs need to be stopped. Over time the cat will have become dependent on corticosteroid administration, so stopping treatment immediately can have severe consequences. The dose of the corticosteroids must be gradually reduced over a period of time. The time required for weaning off the treatment will depend to some extent on the dose and length of time the cat has been receiving the corticosteroids.

When the disease is caused by an adrenal tumour, the best treatment is for that adrenal gland to be removed (adrenalectomy). This surgery is fairly high risk because the high levels of circulating cortisol predispose the cats to infections and thromboembolism (blood clots) and reduce wound healing. In addition, the adrenal glands are situated very close to a large major blood vessel (caudal vena cava) so severe haemorrhage is another potential complication.

Treatment of pituitary tumours is even more problematic, as there is no one satisfactory treatment available. In humans the treatment of choice is surgical removal of the pituitary tumour (hypophysectomy). This is extremely difficult surgery and although it is being attempted in some parts of the world, it has only been performed in a very small number of cats to date.

Another potentially useful treatment for pituitary tumours is radiation therapy. However, this treatment is not widely available, and again not many cats have been treated in this way. It still remains to be seen how successful radiation therapy is, and what side effects may be encountered.

A wide variety of medical treatments have also been tried for both adrenal and pituitary dependent Cushing's syndrome, such as ketoconazole, metyrapone and aminoglutethimide. Unfortunately, there has been very variable success with these drugs, with some cats not responding to treatment at all. Mitotane used to be the treatment of choice for dogs with this disease, but this drug appears to have little effect on the disease in cats. Recently, a newer drug, trilostane, has been licensed for the treatment of Cushing's syndrome in dogs, and has become the treatment of choice in dogs. Trilostane has not yet been widely used in cats but may prove to be a useful treatment in the future.

What is the prognosis for cats with Cushing's syndrome?

Cushing's syndrome is a serious disease and carries with it a guarded to poor prognosis. Treatment options are very limited, treatment can be expensive, stressful for the cat and owner and, unfortunately, there is no guarantee of treatment being a success. Even with 'successful' treatment, less than 50 per cent of cats afflicted with the disease will survive beyond a year. Hopefully, in the future newer treatment modalities will become available improving the outlook of cats with Cushing's syndrome.

Updated November 2008