What is Cushing’s Disease in Dogs and How Canine Cushing’s Disease Can Benefit from Genetics Research

Introduction to the Endocrine System

In a healthy dog, the endocrine system is a finely tuned “machine”, composed of different “parts” (the organs) that communicate with each other via chemical signals called hormones in order to keep each other in check. One of the main organs of the endocrine system, the pituitary gland, is located in the brain and, among other hormones, secretes adrenocorticotrophic hormone (also known as ACTH). As the name implies, this hormone’s action is directed towards the adrenal glands, located far from the pituitary gland, in the area of the kidneys.

As a result of the presence of ACTH in the blood, the adrenal glands secrete glucocorticoids, or cortisone-like chemicals; specifically, they secrete cortisol. Cortisol is involved in many important processes in a healthy body, like the regulation of fat metabolism, immune responses, blood sugar levels and kidney functions. The fine-tuned endocrine system makes sure that just the right amount of cortisol is in the blood; indeed, high levels of cortisol in the blood are a signal for the pituitary to stop secreting ACTH. No more ACTH, no more cortisol. If cortisol levels are low, the pituitary steps up its secretion of ACTH. Therefore, both the adrenal glands and the pituitary glands are constantly communicating with each other to ensure a “dynamic equilibrium” of cortisol in the blood.

Cushing’s Disease in Dogs

In canine Cushing’s disease, this balance is essentially upset. Indeed, another name that very accurately describes Cushing’s disease is hyperadrenocorticism; essentially, Cushing’s disease (also known as Cushing’s Syndrome) involves a disruption in the balance between the pituitary and the adrenal glands and an over-production of cortisol. The excessive administration of corticosteroids given to treat inflammatory diseases could cause this over-production; this is known as iatrogenic Cushing’s disease and is easily treated by simply discontinuing the medication.

Cushing’s disease in dogs can also occur naturally and has one of two causes, both involving tumors.

• The most common cause of canine Cushing’s disease is the presence of a tumor in the pituitary gland, similar to what occurs in humans. The presence of this tumor causes the excessive secretion of ACTH, no matter what the blood levels of cortisol; as more and more ACTH enters the blood, the adrenal glands respond with the non-stop production of cortisol. About 80-85% of Cushing’s disease in dogs is caused by a pituitary tumor.

• The second type of tumor to cause hyperadrenocorticism is located in the adrenal glands themselves. This tumor leads to the increased production of adrenal hormones, including cortisol, regardless of the presence or absence of ACTH. Essentially, the adrenal glands stop listening to the pituitary and continue to secrete cortisol non-stop. Between 15-20% of canine Cushing’s disease is caused by a tumor in the adrenal gland.

Treating Cushing’s Disease in Dogs

If cortisol is such a necessary part of bodily processes, is it bad to have too much of it? The answer is a resounding yes. Excessively high levels of cortisol lead to high blood pressure, increased susceptibility to diabetes and skin infections, nervous system diseases and weakening of muscles, including the heart. Some symptoms of the disease to look out for in your dog include increased drinking and urination, symmetric hair loss on both sides of the body and increased appetite. Once a dog presents with any of these symptoms, a veterinarian can perform a number of screening tests to more accurately diagnose Cushing’s disease. The most common tests are the low dose dexamethasone suppression test and the urine cortisol:creatinine ratio.

Treating Cushing’s disease in dogs often depends on what the cause of the disease is determined to be. As mentioned previously, iatrogenic Cushing’s disease is treated by simply discontinuing the offending medication. Naturally occurring Cushing’s disease caused by an adrenal tumor is often treated by removing the tumor.

When the cause of canine Cushing’s disease is found to be a pituitary tumor, removal of the tumor is not usually an option. For these dogs, treatment is usually “symptomatic”, i.e. the symptoms are treated, but the disease is never cured. A drug called Lysodren is often used, though research is being done to find other treatment options. Lysodren works by actually killing off part of the adrenal gland, thereby decreasing its ability to secrete cortisol. Needless to say, a dog on Lysodren must be very closely monitored to make sure the amount of the drug administered is not causing more harm than good.

Genetics of Canine Cushing’s Disease

Because many cancers have a genetic component to them, or at least proneness to cancer often has a genetic component, genetics researchers have started to try to unravel the genetics of Cushing’s disease in dogs. Also, it has been found that some breeds are more prone to developing Cushing’s disease, such as Poodles, Cavalier King Charles Spaniels, Boxers and Dachshunds; this lends further weight to the idea that Cushing’s may be a genetic disease, at least in dogs. Research into the genetics of canine Cushing’s disease is aimed at not only finding a cure for the disease, but also at finding a relatively effective “screening test” for the disease. If a dog is found to have a gene or genes for Cushing’s, he or she can be prevented from breeding and perpetuating the disease in the canine population. In this way, even if a cure cannot be found, at least the incidence of the disease among dogs can be driven to near zero.

References

https://www.vetinfo.com/dcushing.html

https://www.peteducation.com/article.cfm?c=2+2097&aid=416

https://www.dogbiz.com/dogbiz-genetic-disease-guide.html#71

Giacomini et al. “Differential Gene Expression in Models of Pituitary Prolactin-Producing Tumoral Cells.” Hormone Research. 2009.

De Marco V et al. “Mutation Analysis of TPIT in Poodle Dogs with Cushing’s Disease.” Pesquisa Veterinária Brasileira. 2009.