Cushing’s disease in dogs, also known as hyperadrenocorticism, is an endocrine abnormality that is characterized by the abnormal secretion of the hormone adrenocorticosteroid hormone leading to a commensurate increase in cortisol secretion from the adrenal glands. Cortisol is secreted by the adrenal glands in response to stimulation from the pituitary gland. Cortisol is responsible for a variety of physiologic processes in the dog’s body including gluconeogenesis for emergency glucose needs especially in times of stress, suppression of the immune system, and support in the metabolism of fats, carbohydrates, and proteins.
Normally, stimuli reaching the anterior pituitary gland stimulate this gland at the base of the brain to release the hormone adrenocorticotropic hormone or ACTH. This hormone then stimulates the adrenal cortex to synthesize and secrete the glucocorticoid hormone known as cortisol. This sends a feedback to the anterior pituitary gland to stop synthesizing and releasing ACTH so that the level of cortisol will not be unnecessarily increased.
Unfortunately, a problem exists along this axis in dogs with Cushing’s disease. Diagnosing it can be quite tricky as there are plenty of disease processes that mimic its clinical course. Of equal importance is the health history of your pooch so that your vet can determine the most appropriate treatment based on the most likely cause of its hyperadrenocorticism or hypercortisolism.
What Causes Canine Cushing’s Disease?
The main pathology in canine Cushing’s disease is the abnormally increased production or synthesis of the hormone ACTH and cortisol. There are two principal causes of Cushing’s disease in dogs and we are going to explore both in this article.
Benign tumors of the pituitary gland are the most common cause of Cushing’s disease in dogs. This is not to say that malignant tumors cannot produce the same disease. It just so happens that majority of the dogs that have this disorder have been observed to have non-malignant tumors in this part of their endocrine system. Tumors in the pituitary gland account for about 80 to 85 percent of all cases of hyperadrenocorticism in dogs. Pituitary tumors cause an increase in cortisol because the tumor itself secretes ACTH even without the necessary stimulus for it to synthesize and release the hormone. Since there is increased ACTH released by the tumor, there is a corresponding increase in the amount of cortisol released by the adrenal glands; again, even without the actual need for it.
There are also tumors that can occur in the adrenal gland itself, accounting for the remainder of cases of naturally-occurring canine Cushing’s disease. Do take note that, unlike pituitary tumors, there is an equal chance that the adrenal tumor can be either malignant or benign. Like pituitary tumors, adrenal tumors produce cortisol independent of stimulation from the pituitary gland’s ACTH.
While tumors in the pituitary and adrenal glands account for close to 100% of all hyperadrenocorticism cases in dogs, there are very rare instances when the cause is a tumor located outside the pituitary-adrenal gland axis. Small cell lung cancer has been known to produce ACTH, too, often via activation of the hypothalamic hormone, corticotropin releasing hormone or CRH. This also means that any tumor that can stimulate the release of CRH has the potential to stimulate the release of ACTH, hence the increase in cortisol.
The administration of certain medications has also been implicated in the development of canine Cushing’s disease. These typically include corticosteroids that are often indicated in the management of canine osteoarthritis, certain types of canine cancers, severe allergies, immune disorders, inflammation, or even as a means to suppress the immune system in an effort to prevent organ transplant rejection. In some instances, synthetic glucocorticoids are also given to dogs as replacement therapy especially when they have unusually low glucocorticoid levels. Since you are essentially giving your dog an active, albeit synthetic version of the hormone cortisol, Cushing’s disease is a very likely complication.
It should also be understood that certain breeds of dogs are more predisposed to the development of Cushing’s disease. For example, poodles, dachshunds, beagles, Boston terriers, and boxers are just some of the dog breeds that are known to have an increased propensity for the development of hyperadrenocorticism or hypercortisolism.
Whatever the cause the condition almost always affects dogs that are already in their middle-age years, typically 8 years and upwards. What this essentially means is that, even if your pooch is not genetically inclined to develop this disease, there is a slight chance that it will have such a condition once it reaches this particular age.
What are the Different Signs and Symptoms of Canine Cushing’s Disease?
Since the main problem in adrenohypercorticism is in the abnormally excessive levels of cortisol without any physiologic need for its increase, its clinical manifestations can be quite extensive. One has to understand that cortisol itself has many physiologic actions or effects. In a dog that has Cushing’s disease, you can, thus, expect these manifestations to be somewhat heightened.
The following is a list of the most common symptoms and signs that are attributed to increased cortisol levels. Do understand that not all of these clinical manifestations will be present in any given dog. Moreover, many of these manifestations are not exclusive to canine Cushing’s disease. It is for this very reason that you have to bring your pooch to the vet if you suspect your dog to have hyperadrenocorticism so your vet can perform a very thorough assessment, allowing for a more accurate diagnosis.
- Increased frequency and volume of urination (polyuria)
- Increased sensation of thirst (polydipsia)
- Increased sensation of hunger (polyphagia)
- Unexplained obesity or sudden weight gain
- Increased panting behavior
- Unusual fat pads located on the dog’s neck and shoulders
- Lethargy and / or lack of energy
- Muscle weakness
- Unusual shedding or loss of hair
- Recurrent infections of the ears, skin, and urinary tract, among others
- Inability to get pregnant
- Hyperpigmentation or darkening of the dog’s skin
- Presence of white, scaly, and hard patches or growths on the dog’s joints
- Inability to sleep
- Unusual thinning of the skin
- Unexplained bruising
- Unusual pot-bellied appearance
- Circling behavior and other behavioral changes
- Seizures and other neurologic abnormalities
Among these clinical manifestations, 17 out of 20 dogs with the disease often present with polyuria and polydipsia. Polyuria occurs because of the diabetogenic effects of cortisol which increases osmotic diuresis. The increased levels of glucose in the blood necessitate its removal in the urine. Unfortunately, this also causes excessive amounts of water to be drawn into the urine. The resulting increase in blood osmolality sends signals to the brain to increase its water intake as a means of compensating for the water losses in the urine. As such, whenever there is increased urination in your dog, you can almost always expect an increase in thirst, too. What this typically implies is that, even if your dog has been properly housebroken there will be many instances of urinary ‘accidents’ because of the unusual speed at which urine is produced and the consequent filling of the urinary bladder.
Another manifestation that is crucial to the diagnosis of Cushing’s disease in dogs is polyphagia. Again, this is often attributed to the diabetogenic effects of cortisol. Since there is not enough glucose moving into the cells, these cells starve. They send messages to the brain telling it that the cells are hungry and that they need glucose. This stimulates the hunger drive in dogs. You may often see your pooch stealing food from your table or even scavenging for food scraps from the garbage can. You might even notice it as begging continuously to be fed. In some instances, they may even get overly protective of their food. You might interpret these as signs of god appetite, but, what you don’t know is that your dog is already showing one of the classic signs of Cushing’s disease.
Abdominal enlargement also occurs in 4 out of 5 dogs affected with the condition. This is often brought about by the redistribution of fat towards the visceral cavity of the abdomen coupled with significant weakening and wasting of the muscles found in the dog’s abdominal region.
At least one out of 2 dogs will present with excessive shedding. Hair loss as a result of Cushing’s disease typically starts in areas over bony prominences such as the elbows. From here the loss of hair progresses towards the dog’s sides and abdomen. What you will typically have is a dog that has hairy head and extremities but none on its body. The skin gets relatively thin, too, making it more susceptible to damage. And because of the diabetogenic effects of cortisol, any injury to the skin is bound to take a long time to heal.
These clinical manifestations are typically taken together in the light of other assessment parameters such as those coming from your dog’s health history, medication history, and laboratory and diagnostic tests. It is, thus crucial for your vet to take a closer look at these signs and symptoms.
What are the Different Types of Cushing’s Disease in Dogs?
Based on what we have already discussed about the most likely causes of Cushing’s disease in dogs, we can classify the veterinary condition into three distinct types, although only two can be considered of medical importance.
- Pituitary dependent
This type of Cushing’s disease in dogs is the most common. As we have already noted above, it affects between 80 and 85 percent of all dogs that have the condition. In some instances, it can even reach up to 9 out of 10 dogs. The most common cause is a benign adenoma that develops in the anterior pituitary gland. It is this adenoma that secretes adrenocorticotropic hormone, stimulating the increased synthesis and secretion of cortisol from the adrenal cortex.
- Adrenal dependent
As the name implies, this Cushing’s disease type is caused by a tumor in the adrenal cortex. It accounts for almost 20 percent of all hyperadrenocorticism cases and is most often due to adrenal gland tumors. Do take note that adrenal tumors are not the only cause of such a dysfunction in the secretion of cortisol.
Other anatomical and histological abnormalities of the adrenal gland can contribute to the disease. For example, hyperplastic adrenal glands have also been implicated in the development of the canine disease. Hyperplastic conditions are not yet neoplastic or cancerous cell formations. Rather, it can be viewed as the beginning stage of adrenocortical carcinoma. In this condition, there is an increased reproduction of adrenocortical cells such that the increase in number of these cells naturally increases the synthesis and secretion of cortisol.
Another condition of the adrenal gland which can contribute to Cushing’s disease in dogs is the development of nodules in the adrenal gland often in combination with hyperplasia. These nodes are not, in any way, cancerous, yet they provide the necessary impetus for the increased secretion of cortisol.
Cushing’s disease as a result of the prolonged administration of synthetic corticosteroids or the administration of unusually high concentrations or doses of glucocorticoids is classified as iatrogenic Cushing’s disease. The good news with this kind of Cushing’s disease is that it can be easily managed. The synthetic glucocorticoid is gradually withdrawn to help prevent any rebound effects. Once it has been completely eliminated, the symptoms should begin subsiding.
How Canine Cushing’s Disease is Diagnosed
While there are clinical manifestations that can almost instantly point to the diagnosis of Cushing’s disease, veterinarians will typically employ a variety of assessment methods to confirm the diagnosis. This is important since the definitive treatment will depend on the accuracy and validity of the clinical diagnosis. Cushing’s disease in dogs is typically diagnosed using the following methods.
- Urine analysis
Analyzing the specific gravity of urine is often an important first step in the correct identification and determination of Cushing’s disease. This is related to the symptom of polyuria leading to a heavily-diluted urine and consequently a urine with a low to very low specific gravity. If this is observed, the dog is then subjected to further tests to make sure that the dilution of the urine is brought about by Cushing’s disease and not because of diabetes mellitus or other disease processes.
- Blood tests
Some of the more common possible indicators of Cushing’s disease in dogs include elevations in the levels of the liver enzymes ALT and AST as well as cholesterol. There may also be a reduction in blood urea nitrogen (BUN) as a result of increased urination.
- Cortisol-to-creatinine ratio
This is not really a diagnostic test since it only screens for the presence of cortisol in the absence of stress. Remember what we said about cortisol being released because of stimulation by ACTH from the pituitary gland? One of the stimuli for ACTH secretion is stress. Normally, if there is stress, the normal response is to release ACTH to stimulate cortisol secretion. As such, when cortisol is found in an otherwise relaxed, un-stressed dog, then there is a good chance that Cushing’s disease may be present. For this to be tested, a urine sample is obtained from your dog in the home preferably during its most relaxed, calm state. The urine sample is sent to the veterinary clinic for laboratory urinalysis testing, specifically looking for the ratio between cortisol and creatinine. If it is sufficiently high, then your vet may call for definitive diagnostic tests.
- ACTH stimulation test
In this test, synthetic ACTH is introduced into the dog’s body in the hope of eliciting a response from its adrenal glands. If synthetic ACTH is not available, tetracosactide or alsactide can be used. While this test does not differentiate between pituitary and adrenal Cushing’s disease, it is often beneficial in the diagnosis of more difficult cases.
- Low dose dexamethasone suppression test
This has become the screening test of choice when it comes to determining the presence of Cushing’s disease in dogs. Low dose dexamethasone is administered into the dog’s system with the aim of eliciting a response which is to lower the levels of blood cortisol within 8 hours. Dexamethasone is a synthetic corticosteroid which, when introduced into the body, can help provide the necessary feedback mechanism to the pituitary gland that there is sufficient glucocorticoids in the blood. This lowers ACTH secretion, lowering cortisol secretion. If cortisol levels are not reduced 8 hours after the administration of low dose dexamethasone, this is usually interpreted as a good indicator of Cushing’s disease.
- High dose dexamethasone suppression test
If your vet would like to distinguish between the two types of hyperadrenocorticism, a high dose dexamethasone suppression test may be advised. However, this screening test is rarely indicated as the LDDST is often enough to differentiate between the two.
- Abdominal ultrasound
There are three fundamental reasons why an abdominal ultrasound is often indicated in dogs suspected of having Cushing’s disease. Ultrasound imaging can help establish the anatomical integrity of the various organs within the dog’s abdomen. More specifically, it helps provide a clearer picture of the shape and size of the adrenal glands. This can help differentiate between pituitary and adrenal hyperadrenocorticism. If the adrenal glands are normal in size and shape, then it is possible that the dog has the pituitary type of disease. However, if the adrenal glands are larger or have an uneven shape, then an adrenal type of Cushing’s disease may be present. Lastly, ultrasonic imaging can help determine whether the adrenal gland tumor has already spread to other organs or not yet.
- Other tests
Other diagnostic tests may include fecal examination and complete blood cell count, the latter of which may help uncover potential abnormalities in white blood cells.
What are the Treatment Options for Dogs with Cushing’s Disease?
Treating Cushing’s disease in dogs lies in the underlying cause. Since tumors account for majority of the cases of Cushing’s disease, then it is highly expected that the surgical removal of these tumors is necessary. This is often indicated in adrenal dependent Cushing’s disease as it is a lot easier to excise the tumor growth from the adrenal glands than in the pituitary gland.
For pituitary dependent Cushing’s disease, surgery is not usually the first choice since accessing the pituitary gland can be quite tricky. Also, because of advances in pharmacotherapy, the use of non-surgical methods in treating this type of Cushing’s disease is made a lot easier. Here are some of the more common medications currently used in the treatment of Cushing’s disease.
- Lysodren: This is the medication of choice for pituitary type of Cushing’s disease. It destroys adrenal gland cells that produce glucocorticoids. The net effect is that even in the presence of high levels of ACTH from the pituitary gland, its physiologic effects will be very minimal since there will be fewer adrenal cells producing cortisol. The problem, unfortunately, is when there is a great number of adrenal cells that are destroyed, in which case synthetic glucocorticoids will have to be administered, albeit in the long term. Lysodren is inexpensive and quite effective. Sadly, its serious side effects often pose great concern.
- Trilostane: This drug is more expensive than Lysodren and is considered to be more effective in the management of Cushing’s disease brought about by adrenal gland tumors. Constant monitoring and repeated examinations are required to evaluate the effects of the therapy.
- Ketoconazole: This is an antifungal medication that has been extensively used in the management of hyperadrenocorticism since the middle of the 1980s. It works by harnessing one of the side effects of ketoconazole which is the limitation of the production of steroid hormones. Today, ketoconazole is rarely used, although a few vets still recommend it.
- Selegiline: Also known as L-deprenyl, this monoamine oxidase inhibitor, has also been used in the management of Cushing’s disease in dogs. However, there is controversy regarding its effectiveness since it is believed to offer only symptomatic relief and not the actual management of the root cause of the disease.
Cushing’s disease in dogs is a serious endocrine abnormality brought about by tumors to the pituitary gland or the adrenal glands or even by the indiscriminate use of synthetic corticosteroids in dogs. Since there are a lot of manifestations that can mimic other diseases, it is imperative that a veterinary consult be obtained to ensure a more comprehensive assessment and confirmation of the disease. This way, more appropriate treatment can be planned and implemented.