Drovers Vet Hospital

What is Cushing's Disease?

Cushing's Disease is a disease in which the adrenal glands overproduce certain hormones. The correct 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 which is commonly and incorrectly known as ‘cortisone’. Either deficient production or excessive production of these substances may be life-threatening.

How does this disease occur?

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 cause, however, because the various forms are treated differently and have different prognoses.

Iatrogenic. Iatrogenic Cushing's Disease means that the excess of ‘cortisone’ has resulted from excessive administration of synthetic cortisones. This may occur from oral or injectable medications over a long period.. Although the injections or tablets were given for a legitimate medical reason, their excess is now detrimental. Occasionally use of ointment containing cortisone or its derivatives over a long period of time can result in excessive intake due to absorption through the skin or eyes or to the dog licking the product.

Adrenal gland tumour (15-20% of cases). Cushing's Disease may be the result of a benign or malignant tumour of the adrenal gland. Benign tumours occur in about 50% of cases. The biggest problem with these growths is either spread to other organs (in malignant cases) or expansion of the growth thus putting pressure on important blood vessels (both benign and malignant cases).

Pituitary gland tumour (80-85% of cases). The most common cause of Cushing's Disease is a tumour (growth) of the pituitary gland. The tumour may be either benign (in 90-95% of cases) or malignant (rare cases). The tumour causes the pituitary to overproduce a hormone which stimulates the adrenal glands. Excessive cortisol secretion results. The tumour may be either microscopic or quite large. Depending on the size of the tumour, the presence of signs other than Cushing's will be variable. Generally, if the activity of the adrenal gland can be controlled, the dog will live a relatively normal life. 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 (called monitoring).

What are the clinical signs?

The most common clinical signs associated with Cushing's Disease are a tremendous increase in appetite, water consumption, and urination. Lethargy, or lack of activity, and a poor hair coat are also common. Many of these dogs develop a bloated 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. The skin frequently appears paper thin. Panting is another common finding with this disease.

How is it diagnosed?

Diagnosis of Cushing’s Disease can be really tricky in some cases and often requires a number of tests to be performed to firstly make the diagnosis and then secondly find out wich type is present (i.e. Adrenal vs Pituitary). All these tests involve taking blood samples, sometimes at timed intervals. Although some of these tests are expensive, they are necessary for a definitive diagnosis. In most cases, general blood tests are done first and these may give some indication of the possibility of Cushing’s Disease. Once the possibility is established, more specific tests will need to be performed and this often requires 2-3 blood samples to be taken over a specific time in response to 1 or 2 injectable substances (called an ACTH Stimulation test or a Dexamethasone Suppression test). The majority of patients can be diagnosed with Cushing’s Disease based on the results of these tests and an ultrasound is then indicated to establish the exact type present. In some cases the above tests may be negative (even though Cushing’s may be present) or fall into a grey area, in which case the tests may need to be repeated or alternative tests performed.

What are the treatment options?

Iatrogenic Cushing's Disease: Treatment of this form requires a discontinuation of the ‘cortisone’ that is being given. This must be done in a very controlled manner so that other consequences do not occur. Unfortunately, it usually results in a recurrence of the disease that was being treated by the ‘cortisone’. Because there may have been adverse effects on the adrenal glands, treatment is also needed to correct that problem.

Adrenal or Pituitary Tumour. Treatment of the adrenal or pituitary-induced form of Cushing's Disease is the most complicated to treat. LysodrenÔ, (mitotane), which is not licensed for use in dogs in our country is a drug that can be used to destroy the abnormal adrenal tissue. Another, more recent drug, Trilostane is now more favourably used in most cases (however it is more expensive and needs to be administered every day versus twice a week with Lysodren). Unlike Lysodren, it does not destroy the adrenal tissue, but rather blocks the production of cortisol from the adrenal glands. Adrenal growths tend to either take higher doses to treat or in some cases even do not respond favourably at all. In a small number of cases, surgical removal of the affected adrenal gland can be done.

Instructions for the treatment of Cushing disease

Lysodren (Mitotane)

Treatment with Lysodren involves an initiating phase and a maintenance phase. The initiating phase (tablets given once/ twice daily) arrests the disease and restores the dog to a more normal state. Some of the clinical signs, especially increased food and water intake, should stop within the first 1-3 weeks. Other signs, such as a poor hair coat or a bloated abdomen, may take several weeks or months to correct. The maintenance phase (tablets given once/ twice weekly) represents the phase of long-term therapy. This phase lasts the rest of the dog's life.

The initiating phase is generally halted once the water intake decreases. The approach is to switch to maintenance phase as soon as this happens, if within the first 10 days. If this has not occurred by 10 days, an ACTH stimulation test will need to be performed to ascertain whether maintenance dosing is necessary. A possible side effect during treatment is that too much adrenal tissue is destroyed by the medication thus resulting in a crisis of too little cortisol in the body. This is a very serious problem requiring immediate intervention. Your veterinary surgeon will have given you precise instructions regarding the medication and when it will be necessary to examine your dog again. However if any of the following occur, please contact your veterinary surgeon without delay.

a) water intake appears to drop dramatically
b) appetite drops dramatically
c) your dog does not eat a regular meal
d) if any vomiting or diarrhoea occurs
e) if your dog becomes unusually listless

If any of the above occur it may be necessary to perform a monitoring blood test (ACTH stimulation test). This will require your dog to be hospitalised for the day or part of the day. If the test is abnormal, the initiating phase will continue. If the test is normal, the maintenance phase will begin.

Trilostane

Trilostane is a newer drug, now readily available for veterinary use, used to treat Cushing’s disease. It does not require an initiation and maintenance phase and is our preferred treatment option. Treatment is usually started at the lower dosage schedule and tablets given once or twice daily. It is very important to make sure that this drug is given with a meal as absorption is significantly increased this way. Giving tablets without a proper meal can thus cause a failure to respond.

Treatment is closely monitored using the ACTH stimulation test (usually done at 10 days, 2 months and then every 3 months after the beginning of treatment. These tests are commence around 4-6 ours after the medication has been given. A potential side effect of trilostane is adrenal necrosis (severe damage to the adrenal gland) and can cause life threatening hormonal deficiencies. It is thus imperative that close monitoring is adhered to at all times.

Other Drugs/ Treatment

As previously mentioned, surgical removal of the adrenal gland can be performed in some cases of adrenal tumours. Other drugs can also be used to treat Cushing’s Disease, should the response to either of the above 2 drugs be sub-optimal.

Monitoring whilst on treatment

In ALL cases – whether on Lysodren or Trilostane, monitoring is essential to obtain correct dosing regimes and prevent excessive destruction of adrenal tissue. This monitoring is usually done in the form of an ACTH stimulation test. Blood is taken (called the basal level) and then ACTH (which stimulates the adrenal glands) is injected. Another blood sample is then taken after 1 hour. Cortisol is measured in both samples and compared. Most cases will require this monitoring to be done at the following times: