Common symptoms of Cushing’s disease include:
• Excessive urination with possible incontinence
• Large water intake
• Ravenous appetite
• Excessive panting, even at rest
• Muscle wastage and weakness
• Frequent urinary tract infections (cystitis)
• Pot-bellied appearance • Lethargy
• Hair loss, thin skin and recurrent skin infections
To understand Cushing’s disease, or hyperadrenocorticism (HAC), we must first examine the normal function of two little glands called the adrenals. These tiny organs are located just in front of each kidney (ad/renal). They derive their blood supply from, and even resemble tiny kidneys. And when they malfunction, the first sign of a problem may also relate to kidney function.
The adrenals are endocrine glands. That is, they secrete hormones that affect other parts of the body. Those hormones include cortisol and adrenaline, among others. As long as they do their job well, these hormones are produced in small amounts, and help the body deal with stress, inflammation, pain, hydration and urine production, electrolyte balance, and numerous other functions. Problems come when these hormones are secreted in amounts either too low—as in Addison’s Disease—or too high, as in Cushing’s disease.
To further complicate the picture, there are two possible reasons why the adrenals might produce excess amounts of cortisol, and both look about the same at first glance. The obvious issue would be an abnormality in the gland itself, usually a tumor called adenosarcoma. Statistically, this is the case in about one in five cases of clinical Cushing’s disease, and in fact is harder to treat than the other, more common type.
At least four of five cases are what’s called pituitary-dependent hyperadrenocorticism, or PDH. The rest of this article will focus on PDH.
Most people may recall the pituitary gland from junior high school. It is a busy little gland that lives at the base of the brain. It makes all sorts of hormones, such as growth hormone, and others that stimulate various glands in the body such as the thyroid and gonads—and of course the adrenals— to produce their assigned hormones. It may help to think of it as a control panel. A normally-functioning pituitary gland constantly monitors levels of those secondary hormones in the blood stream, and sends out signals— stimulating hormones—when the levels get low. But sometimes this feedback loop malfunctions and something goes wrong. The result in the case of the adrenals is PDH.
So how do you know if your dog might have Cushing’s disease? A diagnosis requires specialized laboratory testing, but this is typically done only when the veterinarian has a reason to suspect it. The most common complaint people have in the early stages is that the dog is drinking a lot more water than usual, and urinating more. In fact, they may even have accidents in the house if they can’t get outside readily. Of course, there are not specific symptoms and could be related to a number of other conditions as well, but this symptom should always trigger a veterinary visit—bring a fresh, clean urine sample with you!
Longer-term signs include increased appetite, with initial weight gain but eventually muscle wasting and variable appetite; hair loss, especially on the tail and belly but ultimately affecting the entire body. Routine blood tests typically show an increase in the liver enzyme ALP (alkaline phosphatase), and decreased concentration (specific gravity) in the urine—neither of which is diagnostic, but together they may raise the veterinarian’s suspicion for Cushing’s Disease.
While Cushing’s isn’t fatal by itself, it does lower the body’s ability to fight infection, impairs normal healing, and can predispose to other conditions such as pancreatitis and diabetes, even heart failure. Clearly, these conditions can be fatal, even if treated. The suppressed immune system effects may also leave a dog vulnerable to severe dental disease, urinary-tract infections, liver damage and skin infections, any of which may lead to misery and complicate the diagnostic process.
So, what test is best? Unfortunately, that question has no easy answer. Numerous tests exist involving urine, blood, and “response” tests where a hormone that normal affects cortisol secretion is injected into a vein and samples taken before and after, for comparison of cortisol values. The problem is that no one test is perfectly accurate. In general, the easier and less expensive a test appears, the less reliable it is. While most experts agree that the single most accurate test is the “low-dose dexamethasone suppression” (LDDS), this takes 8 hours and requires three blood draws. At present, it’s the only routine lab test that differentiates between HAC and primary adrenal tumors.
… they may even have accidents in the house if they can’t get outside readily.
Because in most cases the symptoms of Cushings are not specific, and blood tests may not be conclusive, veterinarians will often reach for abdominal ultrasound as a more comprehensive way to look not just at the adrenal glands but also the liver, kidneys and other abdominal organs. This is more expensive, and requires advance scheduling and prep in most cases, but has the advantage of being able to look at all the organs at once.
Once a diagnosis of Cushing’s disease is made, what can be done about it? At present there are two FDA-approved treatments but only one of those, trilostane (Vetoryl®) has proven very effective. In addition, may vets still prefer the more traditional medication mitotane (Lysodren®).
Lysodren® works by destroying the adrenal gland tissue. This effect is dose-dependent, so the idea is to partially destroy both glands, thereby reducing the total amount of gland that is secreting cortisol. Because over suppression is actually more dangerous than Cushing’s itself, this has to be carefully monitored, with frequent testing in the initial stages of treatment and ongoing monitoring for the life of the pet. While the medication is quite expensive, eventually most pets are maintained on one dose every three to ten days, making it fairly convenient and reducing long-term costs.
10-year-old Boxer displaying typical signs of hyperadrenocorticism. PHOTOS © DR. S. GALAC / DECHRA VETERINARY PRODUCTS
Trilostane, which is marketed in the United States under the name Vetoryl®, was initially considered to be a very safe alternative to Lysodren®, and in fact has a lower rate of severe side effects. It is given twice daily, with food. But as we’ve gained more experience with this product, potential serious, even fatal, issues have been identified. As a result, current recommendations for long-term monitoring are fairly similar to those for Lysodren®, but the incidence of serious adverse reactions are considered much lower. Nevertheless, such treatment is a serious undertaking and needs to be closely supervised by your veterinarian.
11-year-old Dachshund displaying typical signs of hyperadrenocorticism.
The test of choice for monitoring response to treatment is the one-hour “ACTH stimulation” test. This involves collecting a blood sample initially, injecting a small quantity of ACTH (adrenal cortical stimulating hormone), and taking another blood sample an hour later. To save money, for monitoring purposes the initial blood sample is sometimes omitted. This is recommended weekly in the initial stages of Lysodren® administration, moving to every three months long term. With trilostane, this is rechecked after 30 days of treatment and if in the target range at that point, at day 30 and then every three months subsequently. This test should always be started two to four hours after the morning dose, which should be given with food. Additional tests will be recommended at varying intervals as well.
Signs of over regulation should be noted immediately. Unfortunately, these overlap with signs of under regulation and include lethargy, increased water consumption, vomiting, and dehydration. If your dog is being treated for Cushing’s, always be on the alert for changes in behavior.
Lillian Roberts, DVM, is the owner of Country Club Animal Clinic, which is located at 36869 Cook Street in Palm Desert. 760-776-7555 www.countryclubdvm.com.