Cushing’s Disease is rather daunting. It is not common, although I do see it.
It involves a gland that affects the production of one of the most essential hormones in a pet’s body. That hormone is commonly known as cortisone. Below, I have outlined how it can affect various body parts. A tumor of the adrenal gland can cause it or result in a tumor in another gland, which affects the adrenal gland.
Cushing’s disease, also called Cushing’s syndrome or hyperadrenocorticism, results from an overproduction of the hormone cortisol. Cortisol is produced by the adrenal glands, located next to the kidneys, and adrenal glands are stimulated to produce cortisol by the pituitary gland at the brain's base. There are two types of Cushing’s disease. In adrenal-dependent Cushing’s disease, an adrenal gland overproduces cortisol because of an adrenal tumor. In pituitary-dependent Cushing’s disease, the adrenal glands overproduce cortisol because a pituitary tumor overstimulates them.
There are many clinical signs associated with Cushing’s syndrome in dogs. These signs usually come on gradually and, because of this slow onset, these changes are often written off as part of the normal aging process. The following list of common symptoms that an owner might observe in their pet at home is: Drinking excessively, Urinating excessively and Incontinence.
Owners often notice that lately, the water bowl must be filled more frequently than in the past. Some dogs are unable to hold their bladder all night and begin crying to go outside during the night when previously this was unnecessary. Also, urinary tract infections may be detected and true urine leaking may be observed. Each day a dog should drink about one cup of water for each ten pounds of body weight, though this can vary somewhat with environmental temperature and activity level.
Dogs with excessive water consumption will consume vastly more than this regularly.
Increased or even Ravenous Appetite: This symptom often leads dogs to beg incessantly or steal food from the garbage. It is important for an owner not to be fooled by the pet’s apparent good appetite: eating well is not necessarily a sign of normal health.
Pot-bellied Appearance: This symptom, present in over 90% of Cushing’s syndrome dogs, results from hormonal redistribution of body fat plus a breakdown of abdominal musculature. Further contributing to the pot belly is an enlarged liver which may bulge a bit especially with weakened abdominal muscles.
Muscle Weakness: Muscle protein is broken down in Cushing’s syndrome. The result may be seen as exercise intolerance, lethargy, reluctance to jump up on furniture or climb stairs.
Skin Disease: The classical signs of endocrine (hormonal) skin diseases are: Hair loss on the main body sparing the head and legs. Thin, wrinkled skin with poor wound healing. Hair that does not grow back after clipping. Blackheads and darkening of the skin, especially on the abdomen. Persistent or recurring skin infections (especially if the dog is not itchy during times when the skin infection is cleared). Another condition of the skin that may be observed is called calcinosis cutis, in which calcium deposits occur within the skin. These are raised, hard, almost rock-like areas that can occur almost anywhere on the body.
Some other notable findings might include: excessive panting and shortness of breath, urinary protein loss, infertility, extreme muscle stiffness (called pseudomyotonia -- a very, very rare symptom in Cushing’s disease), and high blood pressure.
Aside from the symptoms described above, advanced untreated Cushing’s disease puts a dog at risk for the following serious problems: calcium oxalate bladder stones, diabetes mellitus, and pulmonary thromboembolism.
Once a pet has been confirmed as having Cushing’s syndrome, the next step is to determine which form of Cushing’s syndrome the pet has since treatment and prognosis are different for each form. As described, there are two forms, commonly abbreviated PDH stands for pituitary dependent hyperadrenocorticism and accounts for 85 percent of canine and feline Cushing’s patients. In PDH, there is a pituitary tumor, often extremely small, causing overstimulation of the adrenal glands.
"AT" simply stands for adrenal tumor. Adrenal tumors can be benign or malignant. Testing to determine the type or form of Cushing’s disease is called discriminatory testing. This type of testing is done AFTER the diagnosis of Cushing’s disease has already been made. Here are some issues and concerns where the type of Cushing’s disease the pet has becomes an important matter.
If there is an adrenal tumor, there is a 50 percent chance that it is malignant. It is helpful to know if the pet has a condition with this kind of malignancy rate, especially if surgery is being considered. If the patient is known to have an adrenal tumor, this knowledge will direct the doctor on how and where to look for tumor spread to determine if the patient has cancer or not. On the other hand, if the patient is known to have a pituitary tumor, it becomes more relevant to image the brain to look for evidence of pressure on the brain.
Medication protocols may be very different for adrenal tumors versus pituitary tumors. Surgery protocols are completely different for adrenal tumors versus pituitary tumors.
What tests will tell us what type of Cushing’s Syndrome the dog has?
There are several.
The Low Dose Dexamathasone Suppression Test
If you are lucky, the same test used to determine if a pet has Cushing’s disease can also classify Cushing’s disease so that no further tests are needed. To get the information needed, a 4-hour sample is drawn in addition to the pre-dexamethasone sample and the 8-hour sample. If the cortisol level suppresses to a level below 50% of baseline at 4 hours, only to escape to a level high enough to indicate a positive result, only a pituitary tumor is possible. While pituitary tumors do not always show this kind of classic suppression at four hours, adrenal tumors never do. If suppression is seen in the 4-hour sample, further testing is not needed, though this is the only pattern that is distinctive enough to obviate further testing. Approximately 60 percent of patients with pituitary tumors can be identified with the low-dose dexamethasone suppression test.
The High Dose Dexamethasone Suppression Test
This test is similar to the low-dose dexamethasone suppression test except that a higher dose of dexamethasone is used, and the patient has already been diagnosed with Cushing’s. The idea behind is that a patient with a pituitary tumor will show suppression in circulating cortisol when exposed to the high dose of dexamethasone; suppression does not occur with the low dose. If there is an adrenal tumor, suppression does not occur. Unfortunately, the theory does not hold well enough to make this a reliable test; a full 20 to 30 percent of pituitary tumors will fail to suppress even with the high dose of dexamethasone. Furthermore, this test cannot identify patients with adrenal tumors; it can confirm about 70 to 80 percent of patients with pituitary disease. The rest will need further testing.
Endogenous ACTH Level
Many veterinarians feel this is the most accurate method of classifying Cushing’s syndrome, but the problem is that the test is technically challenging to run. Serum from the patient must be frozen when transported to the laboratory and must not thaw. The hormone ACTH is fragile and may not survive the trip to the lab. The idea with this test is that a patient with a pituitary tumor will have high ACTH levels, as this is what the tumor is secreting. A patient with low or no measurable ACTH levels has an adrenal tumor as the pituitary is trying its best not to stimulate the over-active adrenal tumor.
Imaging
Fundamental to discerning pituitary dependent from adrenal tumor is the size and shape of the adrenal glands. With pituitary-dependent disease, both adrenal glands are being overstimulated, so they should both be symmetrical in size and shape and most likely enlarged. With an adrenal tumor, one gland will be severely atrophied and possibly undetectable, while the other is enlarged and possibly misshapen. This difference makes imaging of the adrenal glands an accurate way to distinguish types of Cushing’s syndrome. Ultrasound, MRI, or CT scan can be used; however, ultrasound is the most readily available and least costly. In one study, ultrasound was able to correctly identify adrenal tumors in 86 percent of cases. Sedation is generally not needed for abdominal ultrasound, whereas CT and MRI require general anesthesia and usually needs referral to a specialty clinic.
An added benefit of imaging includes looking for evidence of malignancy should an adrenal tumor be identified. Malignant tumors tend to invade the vena cava, the largest vein in the body. Ultrasound has been found to be extremely accurate in evaluating for this complication. Imaging also allows for taking measurements of the adrenal glands. Glands that measure greater than four cm in length are highly suspicious of being malignant.
It is important to note that ultrasound can never be used to make the initial diagnosis of Cushing’s syndrome as there is too much variability in the size of normal adrenal glands. When it comes to gaining information, imaging is best used on patients already known to have Cushing’s syndrome for whom classification is needed.
Medication protocols may be very different for adrenal tumors versus pituitary tumors. Surgery protocols are completely different for adrenal tumors versus pituitary tumors.
Dr. Lamb is the Veterinarian at the Manchester Animal Hospital.
