Cushing’s disease (hyperadrenocorticism)

Although Cushing’s disease is a severe disease the changes it causes can be quite subtle in the early stages. Many owners do not recognize the signs of Cushing’s disease in their pet, instead confusing the changes caused by the disease with ageing. It is important to get an early diagnosis for this disease because, with treatment, affected dogs can lead a normal and full life.

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 dog 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.
• Respond to stress.

Because cortisol is so vital to health, the amount of cortisol produced by the adrenal glands is precisely balanced. Cortisol production is regulated by hormones produced in the brain (from the pituitary gland). The hormones produced by this gland stimulate the adrenal glands. When the adrenal glands receive the signal from the pituitary, they respond by producing cortisol. 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.

Nearly all 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 few cases of Cushing’s disease are caused by a tumor in the adrenal gland.

The two forms of natural Cushing’s disease are:

• Pituitary-dependent Cushing’s disease: a tumor in the pituitary causes excess production of the hormone, adrenocorticotropic hormone (ACTH) resulting in enlargement of both adrenal glands.
• Adrenal-dependent Cushing’s disease: a tumor of the adrenal gland makes one gland grow bigger and it is therefore able to produce more cortisol.

Sometimes signs of Cushing’s disease are caused by steroids given by the veterinarian to treat another disease, eg allergic skin disease. This will often resolve when the steroid treatment is stopped, but it is important to speak to your veterinarian about weaning your dog off steroids. Stopping steroid treatment suddenly can cause further problems with the adrenal gland.

The signs of Cushing’s disease are extremely variable and can be subtle in the early stages. It is usually not possible to decide which form of the disease is present by the clinical signs. Cushing’s disease affects older pets (over 7 years of age). 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 bi-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 ageing.

Steroid hormones affect almost every tissue in the body and the signs of Cushing’s disease can be diverse. The most obvious sign of Cushing’s disease is increased thirst. If your dog is drinking more (or suddenly needs to get up in the night to urinate) you should always take them to the veterinarian for a check-up. However, not all dogs with Cushing’s disease have increased thirst.

An increased appetite (and weight gain) is also very common in Cushing’s disease, but owners may not recognize this as a sign of illness.

Cushing’s disease causes changes to the skin and haircoat. The hair is lost in patches (particularly over the flanks) but there is no scratching. Other symptoms appear in the skin, which becomes fragile and thin. It bruises easily and heals poorly. Purplish pink stretch marks may appear on the abdomen. Female dogs may stop coming into season.

Steroid hormones cause muscle wasting. Weak muscles may make it difficult for your dog to exercise. You may notice that your dog is panting a lot, or they may develop joint problems. In Cushing’s disease, fat is deposited in the liver making it swell and this may be visible causing the abdomen to hang down with a pot-bellied appearance.

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.

In most cases of pituitary-dependent disease the tumor in the brain is tiny and causes no neurological effects. However, in a few animals the brain tumor is sufficiently large such that it can cause neurological signs eg depression, blindness or seizures.

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 dog. Some of these blood samples have to be handled very carefully and will need to be sent away to veterinary laboratories for analysis.

Ultrasound examination of the abdomen allows your veterinarian to measure the size of each adrenal gland. 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.

There are a number of reasons why examination of a urine sample can be useful in a dog with Cushing’s disease:

Three medications may be used to treat the pituitary form of the disease:

• Trilostane (Vetoryl): this drug is the most common drug used to treat Cushing’s disease in dogs (UK and US). Trilostane inhibits the adrenal glands’ ability to produce cortisol. Unlike mitotane it does not destroy adrenal tissue. It is important to realize that this drug does not do anything to treat the tumor (pituitary or adrenal) causing the disease, but it can be used to control the signs of cortisol excess in dogs with both pituitary and adrenal dependent Cushing’s syndrome. The drug is given as a tablet once (or sometimes twice) daily and it must be given regularly, or hormone levels will rapidly rise again. As is the case with mitotane, routine blood tests are taken three or four times a year to ensure that the treatment does not need to be altered.
• Mitotane (Lysoderen): mitotane is toxic to the part of the adrenal gland that produces cortisol. It destroys the adrenal gland so that is unable to produce so much hormone. Mitotane can also kill cells in adrenal tumors. Remember that most cases of Cushing’s disease are caused by a small tumor in the brain and so mitotane does not usually address the underlying cause of the disease. When treatment is started the drug is given once daily for around 7-10 days. This causes rapid destruction of the adrenal gland. Once levels of hormone have dropped, mitotane is given as a weekly maintenance dose, just enough to kill off any new cells that have grown that week. Routine blood tests are taken three or four times a year to ensure that treatment does not need to be altered.
• Selegilene (Anipryl): approved by the FDA in the USA for the treatment of pituitary dependent Cushing’s disease in dogs. It has not been licensed for the treatment of hyperadrenocorticism in the UK. Unlike mitotane, the drug works at the level of the pituitary to decrease ACTH levels and does not have a direct effect on the adrenal gland. Anipryl is given once a day, has very few side-effects, requires no additional blood tests to monitor treatment and works in about 50% of cases. It cannot be used in dogs with an adrenal tumor.

In a few cases, surgical removal of an adrenal tumor is possible. This surgery is difficult and should be performed by a specialist in veterinary surgery. 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. Your veterinarian may want to start medical treatment before surgery to help decrease the side-effects of high cortisol levels during anesthesia and surgery.

If your dog has signs associated with a mass in the brain, they will need additional treatment; as the drugs available will not affect the size of this tumor. Radiotherapy is available at some specialist hospitals, and this can help shrink the tumor and eventually decrease the levels of ACTH and cortisol in the blood. Unfortunately, because of its location, surgical removal of the tumor in the brain is usually not possible in Cushing’s disease.

Very few side-effects are reported with the use of selegiline. There are few reported side-effects from trilostane provided that careful monitoring is performed. Mitotane is a more potent drug and can have significant side-effects if not used correctly. An overdose of mitotane can completely destroy the adrenal gland and result in a deficiency of the stress hormones. If your dog suddenly shows signs of collapse, trembling, abdominal pain, or any other signs that causes you concern, contact your veterinarian. Close monitoring of dogs receiving treatment with mitotane or trilostane is very important, particularly in the early stages.

Most dogs with Cushing’s disease are middle-aged or elderly and owners sometimes ask if it is worth treating them. Once an animal with Cushing’s disease is stabilized on treatment, they will usually live a normal life (simply taking their tablets on a regular basis). The outcome for dogs with pituitary-dependent Cushing’s disease with treatment is very good. Some signs will disappear quickly and others more gradually. Appetite and water consumption usually return to normal in a few weeks, whereas full return of the fur may take several months. Many dogs go on to live a normal lifespan. Without treatment complications can be significant and will seriously affect the quality of your pet’s life.

What can I do to help my dog when they have been diagnosed with Cushing’s disease?

If your dog is diagnosed with Cushing’s disease, it is important that you can manage their condition in a stress-free way. Cushing’s disease is a condition that will need management for the rest of their life and therefore it is important your pet tolerates their treatment, and you are able to fit the treatment into your daily routine without disruption.

Their medication is important and finding a treat to hide their medication in will be the easiest way to medicate your dog daily. Be aware that some dogs may smell or detect the medication hidden in the treat and begin to refuse the treat because they associate it with something unpleasant tasting or smelling. It is worth giving them a plain treat first, followed by the treat with their medication and then a plain treat again. You can also use the selected treat during training or other opportunities so they do not become suspicious. Change the selected treat, on a regular basis.

Your pet’s medication will need to be given at the same time everyday and their blood tests may be timed around this. Your vet will be able to advise on the best time for their medication and blood tests around this.

Blood tests are taken from your pet’s jugular (neck) or cephalic (front leg) vein. Getting your dog used to sitting whilst you hold their head up and sitting with one front leg extended can reduce their stress levels when visiting the veterinary practice. Stress increases the cortisol hormone, the lower their stress levels at veterinary appointments, the better for the management of Cushing’s disease.

When a dog has Cushing’s disease they will drink more and therefore will want to go to urinate more frequently. It is important they have unrestricted access to water at all times and therefore you may want to add an additional water bowl to your house. They will also require more opportunities to go to the toilet. If you leave your pet home alone, limit this to shorter periods to prevent accidents. These symptoms will improve as their medication works and your routine will be able to return to normal after some time.

Cushing’s disease also causes weakness of muscles and weight gain. It is therefore important to maintain your dog’s exercise routine. Taking your pet for regular walks, ensures your dog continues to use their muscles and they burn calories. The amount of exercise will be dependent on your pet’s health and what they are used to, but if they are able do regular short walks, this can improve your dog’s quality of life.