Anna Tebb MA VetMB MVM CertSAM MRCVS
Dr Ian Ramsey, BVSc PhD DSAM Dip ECVIM MRCVS, University of Glasgow
Canine Cushing´s disease (hyperadrenocorticism (HAC)) is caused by an over production of steroids. This arises due to either increased production of a steroid stimulating hormone (adreoncorticotrophic hormone (ACTH)) by a tumour in the pituitary gland (which is found at the base of the brain), or overproduction of steroids by an adrenal tumour (found just above the kidney). These two forms are called pituitary and adrenal dependent respectively. Although both diseases are caused by tumours, only the adrenal tumours usually spread to other organs. The pituitary tumour usually is very small and does not affect the dogs brain.
Cushing´s disease is one of the most commonly diagnosed hormonal diseases in the dog with an incidence estimated to be around 0.1%. It usually occurs in older animals and breeds such as poodles and terriers have a predisposition to the problem.
Most dog owners don’t notice the onset of Cushing´s disease (hyperadrenocorticism) in their pet as the signs develop gradually (see Table 1). Increases in appetite and weight are frequently mistaken for signs of health. Only when coat changes develop or the increased thirst becomes severe do owners realise that something is amiss and make an appointment to see their vet.
Table 1: Clinical signs of Cushing´s disease § Increased thirst (polydipsia) § Increased urination (polyuria) § Increased appetite (polyphagia) § Pot belly / obesity § Muscle wasting/weakness § Lethargy and laziness § Skin changes such as hair loss § Persistent anoestrus or testicular atrophy § A few patients may become blind, staggery, stiff or wobbly
There are a number of tests that can be performed to investigate if your dog has Cushing’s disease. These normally include blood samples urine samples and X rays. Although non-specific, these tests may help to identify other diseases that may affect which treatment is the most appropriate for your dog.
In addition, specific tests will be needed to confirm Cushing’s Disease. The ACTH stimulation test is simple to perform and will identify approximately 85% of dogs with the pituitary form and 50% of those with the adrenal form. Alternatively, the low dose dexamethasone suppression test (LDDST) will identify 95% of dogs with Cushing's disease. However this test is more time consuming, and incidence of false positives is also higher.
Establishing the cause
It’s important, but not essential, for both prognosis and treatment to know whether Cushing’s disease is the result of pituitary tumours or adrenal tumours. In general, pituitary abnormalities account for 80% of cases.
In many veterinary practices, the easiest method is measurement of endogenous ACTH concentration. Adrenal ultrasonography, if available, is a quicker alternative but does require specialist experience and training. In some cases the patient may have to be referred for this procedure.
For those rare dogs that have mild neurological signs and suspected Cushing´s Disease, a brain scan (MRI or CT) can be used to check if the pituitary tumour has become very big.
Treating Cushing´s disease
It is important to remember that no particular treatment is right for all patients, all of the time. In the case of pituitary tumours, drugs such as trilostane can be used to control the size and activity of the adrenal glands. Although adrenal tumours can be treated with the same drugs, the response, and the doses required to achieve that response are more variable. Surgical removal of the adrenal tumour is an alternative but requires specialist surgery and intensive post-operative care.
Trilostane is a steroid enzyme synthesis inhibitor. It is short acting and needs to be given once, or sometimes twice, daily. It appears to be effective in many, but not all, dogs with Cushing’s disease. It is safer to handle than mitotane and is also less likely to result in an addisonian crisis.
ACTH stimulation tests will need to be carried out to monitor the patient’s progress. These tests should be performed 4 to 6 hours after trilostane has been administered. Over-dosage with trilostane can cause lethargy, vomiting and diarrhoea and more severe signs on occasions. If these signs occur then the treatment should be stopped until they go away and your vet should be contacted immediately. It is likely that if the drug is restarted then it will be at a lower dose.
Medical management of Cushing´s disease using o,p'-DDD (Mitotane, Lysodren) was the main treatment for many years for both pituitary and adrenal tumours. However it is a drug that it is more difficult to use than trilostane and if too much is given then it may lead to serious and permanent side effects.
An induction dose is administered once daily with food. Water intake and feeding behaviour must then be closely monitored. Treatment is stopped once the water consumption or appetite starts to decrease. An ACTH test should be performed once these end-points are reached, or before if the dog becomes unwell. Most dogs need 5 to 10 days of induction therapy.
Maintenance therapy is given once weekly and is checked by ACTH stimulation tests initially every month then every 3 months. Over-dosage with mitotane is quite common and manifests as lethargy (+/- vomiting /diarrhoea). If these signs are seen then the mitotane should be stopped temporarily and maintenance doses of steroids (prednisolone) administered.
Although there is no published data on the prognosis of untreated dogs they are likely to suffer from complications of Cushing´s such as recurrent infections, hypertension, cardiac failure, blood clots and infections.
Average survival for mitotane treated dogs is over 2 years but survival periods of 10 years have been reported. Similar data are not yet available for trilostane but several dogs have been successfully managed with this drug for more than 3 years.
Dogs with adrenal tumours live on average about 16 months but side effects of high mitotane doses are frequent. Too few dogs have been treated with trilostane to provide meaningful comparisons.
Further information on Cushing´s disease including recommendations on treatment, drug dosages, and monitoring should be obtained from your veterinary surgeon. They may wish to call a specialist in canine medicine. Please do not contact the authors directly as they are unable to discuss specific cases without the permission of your own veterinary surgeon.
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