What is Cushing’s disease?
Cushing’s disease, more accurately known as Hyperadrenocorticism (or HAC), occurs as a result of an increase in the level of cortisol (produced by the adrenal glands) circulating in the blood, coupled with a failure of the mechanism that normally controls the level within the limits determined by physiological needs.
It is a complex disease that is not easy to diagnose and that can readily be confused with other conditions presenting similar symptoms.
What is the Incidence of Cushing’s disease?
Cushing’s disease is the most common endocrinapathy (disease involving hormones) that occurs in dogs.
People within the breed have expressed concern about the apparent increase in the incidence of Cushing’s but it is not clear whether this is the result of a real increase in the incidence of the disease or whether the apparent increase is due to a greater awareness of the condition coupled with better diagnosis.
The disease seems to be age related. Although it has been reported in dogs from 4 years of age onwards, it is considerably more prevalent in dogs from 8 years old of age, i.e. in middle aged to old dogs. It affects both sexes but there appears to be a slightly greater incidence in bitches.
Although all breeds of dogs may be affected, some breeds seem to be more prone than others and it is thought that there may be a genetic pre-
What causes Cushing’s Syndrome – the Feedback Principle?
In order to appreciate the basic cause of the condition it is necessary to know something about the mechanism by which the level of blood cortisol is maintained within normal physiological limits.
The hypothalamus (part of the brain) secretes a releasing factor that, in turn, causes the anterior pituitary gland to secrete ACTH (a hormone) into the blood. This ACTH is conveyed in the blood to its target organs, the adrenal glands, where it causes the cells in the adrenal cortex to secrete cortisol, (another hormone) into the bloodstream.
The circulating cortisol is utilised within the body to maintain a whole range of physiological functions.
Receptor cells in the hypothalamus monitor the level of circulating cortisol. If the level exceeds the current physiological needs then the secretion of the releasing factor is shut off thereby curtailing the secretion of ACTH by the anterior pituitary gland. This, in turn, results in a restriction of the amount of cortisol secreted by the adrenal cortex.
Conversely, if the blood cortisol level is too low then the amount of releasing factor secreted by the hypothalamus will increase, resulting in an increased secretion of ACTH and a subsequent increase in the amount of cortisol secreted by the adrenal cortex.
This is an example of a negative feedback system and enables the fine tuning of circulating blood cortisol levels to within the narrow limits that permit normal functioning of the body.
Cushing’s disease occurs when something disrupts this feedback mechanism and there is a build-
The Causes of Cushing’s Syndrome.
The most common cause of naturally occurring (spontaneous) Cushing’s, accounting for about 85% of cases, is the development of a small tumour in the pituitary gland. This type of tumour is typically, but not always, benign. The presence of the tumour results in over-
About 15% of cases of Cushing’s are caused by the development of an adrenal tumour. Usually, only one adrenal gland is affected but cases where both adrenal glands are affected have been reported. About 50% of adrenal tumours are benign and the other 50% are malignant. The presence of the tumour results in that adrenal gland producing an excessive amount of cortisol that, in turn, causes the anterior pituitary to secrete less ACTH. This results in atrophy of the adrenal gland that is not affected by a tumour but the tumour-
Iatrogenic hypercorticism, a non-
What are the Symptoms of Cushing’s syndrome?
Many of the symptoms of Cushing’s syndrome are non-
Generally, the symptoms develop slowly and may be easily missed because the dog does not appear to be ill. Moreover, since Cushing’s is normally a condition that occurs in older dogs, early signs are often assumed to be the result of the normal “aging process” and the dog may have been displaying early signs for some time before the condition is suspected.
Typical symptoms include:-
Additionally, there are often noticeable behavioural changes. The dog may become very lethargic, there may be changes in the wake/sleep pattern and dogs that were previously meticulous in their toilet habits may become increasingly incontinent.
There also appears to be an increasing susceptibility to other infections, particularly those associated with the kidneys and the skin. Heart and lung problems may also occur.
How is Cushing’s Syndrome diagnosed?
Diagnosis of Cushing’s disease is not easy and is often complicated by the need to consider the likelihood of other conditions that present similar symptoms.
There is a twofold aim with diagnostic procedures, namely, to identify and eliminate other possible conditions and to determine whether or not Cushing’s is present and then, ideally, to establish if the Cushing’s is pituitary or adrenal dependent.
If, after a clinical examination and a careful consideration of the case history, Cushing’s is suspected, the veterinary surgeon will explain the testing procedures and arrange for the appropriate tests to be carried out. A screening test is included in order to assess the adrenal gland function.
There is no single screening test that will give a “complete picture” of the situation. The tests vary in their “sensitivity” (ability to accurately detect Cushing’s) and their “specificity” (their ability to detect only Cushing’s). Hence, all are capable of giving false positive and false negative results, and for this reason two (or more) test procedures may sometimes be used in tandem.
Moreover, it may be necessary to repeat the testing procedure in order to obtain a clearer understanding of the situation.
The two most commonly used screening tests are the ACTH Stimulation test and the Low Dose Dexamethasone test. Neither of these tests will differentiate between the pituitary and adrenal forms of Cushing’s and, if this is considered necessary, the veterinary surgeon will arrange for a High Dose Dexamethasone test to be included. Blood samples are taken in accordance with the appropriate test protocol and submitted to a veterinary laboratory for testing.
The results of the tests and an interpretation of these results will be sent to the veterinary surgeon, who will then discuss the laboratory report with the owner and advise on any subsequent action, e.g. need for further tests, treatment, etc.
How is Cushing’s Syndrome treated?
Except in a limited number of situations Cushing’s syndrome cannot be cured. However, the earlier the condition is recognised and treatment is initiated, the better will be the overall outcome. Although life may be extended for a considerable time if treatment is started early enough the primary aim of any treatment is to improve the overall quality of life for the dog.
Several pharmaceutical products have been used for the treatment of Cushing’s syndrome and until recently drugs such as Lysodren (Mitotane) were commonly used. However, Vetoryl (active ingredient: trilostane), the only product that is currently licensed in the UK for this purpose, is now the drug of choice. It acts by inhibiting an enzyme that is essential for steroid synthesis in the adrenal glands, thereby effectively suppressing cortisol synthesis.
The initial dose of Vetoryl for Bedlington terriers is 1 to 2 30mg tablets per day, administered in food each morning. However, in some dogs the effect of the medication appears to be “short-
The treatment protocol published by the manufacturers of Vetoryl recommends that the situation be assessed after 10 days, 1 month and 3 months, then periodically thereafter. A full assessment should also be carried out following any readjustment of the level of medication.
Monitoring is based on a clinical examination of the dog and an assessment of the results of an ACTH Stimulation test taken 4-
It would seem that there is usually a noticeable response within a very short time following the initiation of the treatment regime -
However, it must be remembered that any improvement does not signify a cure and that the dog will usually require daily treatment, and regular monitoring, for life.
Bedlington before treatment The same Bedlington after treatment
(Photographs used with the permission of Roger Bannister, MRCVS)
It is generally recognised that no pharmaceutical product should be regarded as ‘100% safe’. Despite rigorous testing and the development of detailed protocols for their use, there is always the possibility, albeit rare, that an adverse reaction may occur as a result of the use of a product. In such situations the veterinary surgeon must be contacted immediately.
Various alternative types of product, e.g. homeopathic formulations, herbal mixtures, are available for the treatment/control of Cushing’s syndrome. Their use may be warranted in situations where the dog has reacted adversely to conventional pharmaceutical products. However, it is important that this is discussed with your veterinary surgeon, who will be able to give advice on all the options available.
From the Bedlington Terrier Health Group.
A number of Bedlington breeders/owners have expressed the view that there may be a genetic pre-