His name was Lucky. And lucky he was. Although the gelding was diagnosed with equine Cushing’s disease in his teenage years, he had an owner who truly loved him and did everything possible to manage his disease until he was pushing 30. He continued to compete for several years after his diagnosis, was actively ridden into his 20s, and was happy until the end.
In recent years, there’s been a lot of interest in Cushing’s disease, which can’t be cured. We’re learning more every day about how to diagnose and manage this hormonal disorder that’s one of the most common diseases found in horses over 15. If you haven’t encountered it yet, it’s likely that you will. An estimated 10 percent of horses over 15 have Cushing’s, and with all the improvements in horse health care, horses are living longer and longer. That means there’s a good chance you’ll experience this disease sometime in your horse life.
Just 20 years ago, your Cushing’s horse would’ve been retired in the pasture, but no longer. I’m going to show you how you and your horse can live comfortably with Cushing’s disease, just like Lucky did.
The Early Years
Lucky was a successful show horse, and spent his early days on the road, traveling from show to show—working hard and eating well. When he turned 12, his owner noticed that he was slow to shed his winter coat. He seemed to lack energy, and he was getting fat. She started worrying about Cushing’s disease.
Although Lucky was young, relatively speaking, his owner was right: He was showing some early signs of the disease. And she was smart to start asking questions before he developed any more serious symptoms, such as laminitis. The most common signs are a long hair coat that’s slow to shed, lethargy, and weight loss or weight redistribution. The average onset of Cushing’s disease is 19 years of age.
Cushing’s disease originates within the brain. In the normal horse brain, the hypothalamus portion releases a neurotransmitter called dopamine that helps to regulate release of a variety of hormones from the pituitary gland that sits at the base of the brain. One of these hormones, ACTH (adrenocorticotropic hormone), stimulates release of cortisol (the body’s stress hormone) from the adrenal glands.
Equine Cushing’s disease (more correctly called pituitary pars intermedia dysfunction, or PPID) is due to hyperplasia (enlargement due to an increased number of cells) of the “intermedia” portion of the pituitary gland. The pituitary gland in a horse with PPID can be enlarged up to five times normal size. Historically it was believed that when the pituitary gland is enlarged, it puts pressure on the hypothalamus and causes a reduction in the amount of dopamine released.
Current thought is that the condition is primarily a problem of the hypothalamus. Damage to the hypothalamus results in a reduction of dopamine secretion, which then causes enlargement of the pituitary gland. In either case, dopamine no longer inhibits ACTH release like it should—meaning ACTH levels increase, resulting in increased cortisol in the blood. The signs of Cushing’s disease are attributed to increased cortisol levels.
Testing for Cushing's
Lucky’s vet suggested that he be tested for Cushing’s disease. The first test (ACTH) came back negative, but Lucky’s blood insulin levels were high, suggesting that he was insulin-resistant. Although insulin resistance (IR) doesn’t always correlate with Cushing’s disease (see the sidebar on page 50 for more on this topic), it is considered a risk factor—horses with IR are more likely to develop Cushing’s as they age.
A number of different tests are available to diagnose Cushing’s disease, but none are very sensitive when the disease is just developing. Nevertheless, researchers now believe that early detection and initiation of treatment may be important for slowing progression of the disease-possibly avoiding a devastating laminitis episode. If your horse begins to show symptoms but early tests are negative, consider retesting annually, at least until more sensitive tests become available. If you discover that your horse has insulin resistance, his risk for developing Cushing’s down the road is even higher, so you’ll want to pay even more attention.
The most popular test for Cushing’s currently is resting ACTH. This test requires a single blood sample that can be drawn at any time of day. Blood samples must be handled carefully, as the hormone isn’t very stable in whole blood, but most veterinarians are familiar with the handling requirements and can easily perform the test at your farm.
Testing for Cushing’s in the fall months (August through October) is generally discouraged, because normal hormonal fluctuations during this time of year can make it difficult to interpret results. However, one advantage of the ACTH test is that it often can still be interpreted even during this challenging time of year.
The gold standard for Cushing’s diagnosis is the low-dose dexamethasone suppression (LDD) test. This an overnight test that requires testing a baseline blood sample for cortisol, administering a dose of dexamethasone, and testing an additional blood sample 18 to 20 hours later. In a normal horse, cortisol levels will decrease following the dexamethasone; if your horse has Cushing’s, cortisol levels will remain the same. Because there’s some risk of laminitis after dexamethasone administration, this test should not be used on a horse that has laminitis issues. It also shouldn’t be used in the fall.
Finally, because insulin resistance is common in Cushing’s horses, testing blood insulin/glucose levels is often recommended in conjunction with the Cushing’s test. Insulin is a sensitive hormone, and can elevate significantly with stress, disease, or a high carbohydrate meal. For best results, blood should be drawn first thing in the morning before anything but hay is fed. It shouldn’t be performed if your horse is sick or suffering from a laminitis episode.
No treatment was recommended for Lucky after this first test came back negative, but his vet and owner came up with a plan to manage his insulin resistance. He was put on a low-carbohydrate diet, and to keep weight under control, his work schedule was adjusted to include focused conditioning work in addition to his training for the show ring. They also decided to repeat Cushing’s testing at six-month intervals.
Years went by, and Lucky continued to compete successfully. His insulin levels stabilized with careful management of his diet and exercise, but his hair coat seemed to get a little longer every winter. He started to sweat more than normal during work, and he needed frequent body clipping. In the spring of his 17th year, his ACTH level came back high—confirming a diagnosis of Cushing’s disease. His vet recommended he be started on the Cushing’s treatment pergolide mesylate.
Pergolide mesylate is a dopamine agonist. It works by taking over regulation of the pituitary gland, helping to decrease ACTH release and lower blood cortisol levels. Although Cushing’s can’t be cured, administration of this medication can help control symptoms, and possibly slow the progression of the disease. If your horse is showing a lot of clinical signs of Cushing’s disease, your vet may even recommend initiating treatment before the ACTH or LDD tests come back positive.
Because pergolide can have side effects, including a loss of appetite, lethargy, diarrhea, and colic, it’s best to treat with the lowest dose possible. To determine the lowest effective dose, your Cushing’s horse will be started on a standard low dose based on his weight. Thirty to 60 days following initiation of treatment, your vet may suggest rechecking his ACTH levels, and adjust the dose if needed. For the long term, your vet will recommend monitoring your horse’s ACTH levels as well as his clinical signs. It’s likely his pergolide dose will gradually increase with time. (Note: Pergolide isn’t a legal drug for all disciplines, so it’s important to pay attention to the pertinent drug rules if your competition horse is being treated with this medication.)
Beyond medication, a number of management steps can help to control your horse’s symptoms and prevent other complications of the disease. Because increased cortisol levels make your horse more susceptible to infection, regular dental care is extremely important to avoid gum disease and possible tooth loss. Regular trimming and shoeing is also critical to help reduce your horse’s risk of laminitis—probably the most devastating potential consequence of Cushing’s disease. Finally, attention to grooming and regular body clipping will help maintain health of your horse’s skin and coat—a challenge with the long hair and excessive sweating that accompanies the disease.
Lucky continued to compete on pergolide. At 20, he was slowed down a bit and moved from the non-pro division to a job teaching beginning riders just starting their careers. His ACTH and insulin levels were tested every year, and his pergolide dose gradually increased based on these results—along with his vet’s evaluation of his physical condition.
The End Game
When Lucky turned 24, it became difficult to control his ACTH levels, even with a very high dose of pergolide. He no longer shed at all during summer months, and he experienced his first laminitis episode. He had to be retired from riding. Because he was at the maximum recommended dose of pergolide, his vet suggested adding the medication called cyproheptadine to his treatment plan.
Cyproheptadine also may be suggested for treating your horse’s Cushing’s disease. This antihistamine may help decrease ACTH secretion, although it hasn’t proven to be as effective as pergolide for controlling the disease. It may be recommended in combination with pergolide in advanced cases when the dose of pergolide needed to control the disease is very high.
When complications such as laminitis appear, treatments such as corrective shoeing and non-steroidal anti-inflammatory medications begin to play a role in managing your Cushing’s horse. Your vet and farrier will need to work together to keep your horse comfortable for as long as possible. Eventually, if not stricken by other mortalities, most horses with Cushing’s fall victim to severe laminitis and have their lives ended by euthanasia.
At age 26, Lucky had a severe founder episode with rotation of both fore coffin bones. Even after aggressive treatment for the acute episode, he remained uncomfortable, and his ACTH levels continued to elevate. His owner opted for humane euthanasia for Lucky, after almost 15 years of successfully living with his disease.
The Politics of Peroglide
Pergolide was first introduced as an effective Cushing’s treatment in the early 1990s. At that time, the drug was readily available and could be purchased in a generic version used for the treatment of Parkinson’s disease in humans. But in 2007, it was pulled from the market because of adverse effects in human patients—leaving us without a source of medication.
Compounding pharmacies stepped up to the plate and began marketing powders, syrups, and even tasty “cookies” containing pergolide. Although these products weren’t FDA-approved, they were widely used and were of great benefit to horses diagnosed with Cushing’s disease.
In 2011, an FDA-approved form of pergolide for horses finally became available. With FDA approval comes quality control, and most experts agree that this medication, called Prascend, is a safer and more reliable way to treat your Cushing’s horse than with the compounded drug. Stability of pergolide is a particularly important concern; the FDA-approved version comes in a blister-package that helps to keep it stable. It’s also more expensive, at a cost of approximately $2/day for a starting dose of Prascend, compared with $1/day or even less for a starting dose of compounded pergolide. If you can afford the extra cost and your horse recently has been been diagnosed with Cushing’s, most veterinarians will advise you to consider Prascend over compounded pergolide.
The more difficult question is what to do if you have a horse that’s been successfully managed on compounded pergolide, and currently requires a higher dose. If you decide to make the switch, the company that manufactures Prascend recommends dropping the dose to the recommended starting dose used to treat a horse that’s just been diagnosed, and increasing the dose as needed. However, this approach can result in severe consequences if cortisol levels spiral out of control. If your horse has advanced Cushing’s disease and is doing well, it might be best to follow the “if it ain’t broke, don’t fix it” rule of management.
What About Insulin Resistance?
Once called “pre-Cushing’s syndrome,” insulin resistance is now believed to be a completely separate problem from Cushing’s disease. However, they’re often seen together.
A horse with insulin resistance has abnormal glucose metabolism. Insulin is the hormone secreted from the pancreas in response to an increase in blood sugar (glucose). This hormone helps move glucose out of the blood and into the cells where it belongs. When a horse is insulin-resistant, his tissues fail to respond to insulin appropriately. Blood glucose stays elevated, and insulin levels skyrocket.
The typical insulin-resistant horse is the “easy keeper,” with fat deposits on his neck, tail head, and other areas of his body. He’s also likely to founder. Unlike with Cushing’s disease, there’s no “pill” to help manage this condition. Instead, careful feeding of a low-carbohydrate diet and an active exercise program are the keys to staying healthy.
Confusion remains about the relationship between insulin resistance and Cushing’s disease. Although they’re two separate conditions that can occur independent of one another, if your horse has insulin resistance he may be at higher risk for developing Cushing’s disease than his non-insulin-resistant friends. And if your Cushing’s horse does have insulin resistance, he’s more likely to experience laminitis with his disease. Because of this relationship and the potential consequences, most veterinarians advise testing for insulin resistance at the same time you test for Cushing’s disease.