The two main endocrinologic concerns in horses are equine Cushing’s disease and equine metabolic syndrome. These disorders are increasing in prevalence as our equine population is better cared for and living longer. These disorders can have two main similarities: 1) insulin resistance 2) the potentially devastating possibility of laminitis. While it is an area of much research, there are still numerous theories as to why these horses are predisposed to laminitis, and it is beyond the scope of this article to discuss them all. However the development of laminitis may be related to the insulin resistance, which is a reduced ability of the body to respond appropriately to insulin released by the pancreas after eating a meal. It is important to understand the signs of insulin resistance and be able to effectively manage these horses to decrease the risk of laminitis.
Equine Cushing’s Disease
The cause of equine Cushing’s disease is a benign tumor, likely caused by oxidative stress, in a part of the horse’s brain called the pituitary gland. It is not a typical neoplastic tumor, rather a lack of regulation of hormone secretion due to alterations in local factors in that region of the brain. This alteration (namely a decrease in local dopamine production) leads to unregulated hormone secretion by the pituitary gland, enlarging this area such that it can be thought of like a tumor. This tumor secretes a variety of hormones, including one called adrenocorticotropic hormone (ACTH) that causes the adrenal gland (in the abdomen) to release increased amounts of steroid (cortisol). The increased levels of circulating hormones cause the typical clinical signs of a long, wavy hair coat that does not completely shed out, abnormal fat distribution (such as the cresty neck) with other areas of weight loss and muscle loss, recurrent laminitis, lethargy or exercise intolerance, increased sweating, increased water intake and urination, and immune system suppression or recurrent infections. Many horses with Cushing’s disease have chronic insulin resistance. By far the most common clinical sign is the abnormal long hair coat (called “hirsuitism”), but not all horses with Cushing’s Disease have hirsuitism.
Equine Cushing’s disease is more common in older horses (in their 20s), but can be seen in horses as young as 7 years old. There is no breed or sex predilection, though ponies do seem to be predisposed to the condition.
Diagnosis of equine Cushing’s disease can be challenging in a horse with mild clinical signs. In an older horse with a long hair coat and laminitis, or other typical clinical signs, diagnostic tests often will not be done because those clinical signs are extremely suggestive of equine Cushing’s disease. However in those horses that do not have the “typical” appearance of equine Cushing’s disease there are several tests available. The dexamethasone suppression test is considered one of the most accurate test. This test generally requires two veterinary visits: at the first visit, blood is drawn to measure the cortisol level and a dose of dexamethasone is given. At the second visit, about a day later, blood is drawn to again measure the cortisol level. The test relies on a normal endocrine negative feedback loop. In a normal horse, a dose of dexamethasone (steroid) suppresses the pituitary gland, telling the gland that it is unnecessary to make more cortisol (steroid made by the body) because some has just been given. Therefore the second blood level of cortisol is very low in a normal horse. In a horse with equine Cushing’s disease, the tumor in the pituitary gland produces cortisol no matter what levels of steroid are in the body, so it does not respond to the dexamethasone the veterinarian administers; therefore the second level of cortisol is not significantly different from the pre-dexamethasone level.
This test is considered to be fairly reliable, but it can have false positive or false negative results. There are also two potential drawbacks: first, it necessitates two visits from your veterinarian, which increases cost. Second, it involves the administration of steroid to a horse that is already possibly predisposed to laminitis. Therefore there is an extremely low risk of precipitating a bout of laminitis. Most practitioners feel, however, that the benefits of knowing the test results often outweigh the risks.
The other frequently used test is measurement of the resting levels of ACTH, one of the hormones that is overproduced by the tumor in the pituitary. This test only requires one blood sample, but your vet needs to know ahead of time to bring a special test tube. This test is fairly accurate, but still can have false positives and false negatives.
It has been shown that no test for equine Cushing’s disease is as accurate in the fall months, therefore most veterinarians will recommend not testing at that time. A variety of other tests exist, and there is ongoing research to develop more sensitive and specific ways to diagnose equine Cushing’s disease in those horses in which the diagnosis is difficult. The astute reader may be asking why we do not just measure Example of a cresty neck cortisol levels, since the overproduction of that hormone is a hallmark of the disease. Unfortunately the daily variations in cortisol levels render this measurement virtually useless.
Treatment is advocated because of the possibly devastating effects of laminitis and immune suppression. Fortunately, there is an effective specific treatment for equine Cushing’s disease called “pergolide.” Peroglide acts like dopamine and works on the pituitary gland to prevent the release of excess hormones from the tumor. It is given as a flavored tablet or liquid by mouth once daily for the rest of the horse’s life. Most of the time a beneficial response is seen in 4-6 weeks, but sometimes the dose needs to be increased or decreased. Pergolide has virtually no known side effects in horses. Sometimes bloodwork will be repeated to help monitor response to treatment.
Several other drugs (such as cyproheptadine and trilostane) have been used to treat equine Cushing’s disease, but none have been shown to have the efficacy of pergolide. Many nutritional or herbal supplements are also available, and may have variable efficacy, however none have been proven to be safe and effective. In addition to daily medication, some feed and management changes should be considered. These horses need regular farrier care, good dental care (immune suppression and older age make them prone to dental problems and secondary sinus infections), routine preventive veterinary care, and good quality feed. Some horses may need to be clipped to help prevent hyperthermia. Generally high starch/sugar feeds should be avoided to help minimize fluctuations in glucose levels because these horses are often insulin resistant. More about nutrition is written in the following section on metabolic syndrome.
Equine Metabolic Syndrome
Metabolic syndrome is defined as horses with chronic insulin resistance, obesity or abnormal fat distribution (the cresty neck), and increased risk of laminitis. These horses do not have equine Cushing’s disease. This is a relatively newly recognized condition, and there is a lot of ongoing research about this disorder and our understanding of it continues to grow.
Example of horse with metabolic syndrome. Note the cresty neck and excess fat by the tailhead.
Horses with this condition tend to be younger than horses with Cushing’s disease. These horses often have increased circulating fat levels.
The cause of metabolic syndrome is not fully understood, but several theories are being closely considered. First, obesity leads to insulin resistance (much like people with Type II diabetes). Second, insulin resistance develops secondary to abnormal nutritional usage in genetically predisposed animals. Lastly, fat cells can be metabolically and hormonally active and alter insulin usage in a peripheral Cushinoid-type syndrome. It is logical to think that horses with metabolic syndrome will perhaps transition into having equine Cushing’s disease as they age; however this has not been proven.
There are several ways to test for insulin resistance associated with metabolic syndrome. The most basic test, often used first, is to measure resting glucose and insulin concentrations. Basically, a normal horse should have low insulin levels when glucose levels are normal. A horse with insulin resistance has increased levels of insulin (to try to make up for tissue resistance to it) in the face of normal or low glucose levels. A second, more involved, test is the combined glucose-insulin test (CGIT), which is used when equine metabolic syndrome is suspected but resting insulin and glucose levels are normal. The CGIT involves placing an intravenous catheter, administering glucose and insulin, and measuring the body’s response to this at multiple time points.
The management of metabolic syndrome and insulin resistance is focused on the goals of reducing weight, dietary management, and increasing exercise. The most important goal of dietary management is to restrict the amount of soluble carbohydrates (previously called “nonstructural carbohydrates”) in the feed, because they alter the insulin levels the most. Hay can be analyzed (your vet can direct you to a company that will do this) for it’s soluble carbohydrate content; it is worth doing this only if you purchase large amounts of hay at a time. Grass hay has fairly low soluble carbohydrates, and should be fed at 1.5 to 2% of body weight, as directed by your veterinarian. Oat hay should not be fed. If the horse’s hay intake is tapered down to 1% of it’s body weight and it is still having difficulty losing weight, soaking the hay is a way to further decrease the soluble carbohydrates. It should be soaked in warm water for 20 minutes, or cold water for 60 minutes, immediately prior to feeding. A vitamin/mineral supplement will need to be fed, and if additional calories are needed they should be provided by sources high in fat and protein, rather than carbohydrates, such as corn oil or rice bran.
Sweet feeds, apples, carrots, and high sugar treats should be minimized or, more often, completely removed from the diet. It is important to discuss pasture access at different times of year with your veterinarian. Several companies also make low-carbohydrate feeds specifically designed for horses with insulin resistance.
Unless a horse is currently dealing with a bout of laminitis, increasing exercise is essential to reducing body fat. Some studies have shown that increased exercise also helps improve tissue insulin sensitivity.
If a horse is on a good exercise program with a proper diet and still not losing weight, thyroid hormone supplementation may be recommended by your veterinarian to “jump start” your horse’s metabolism. Many horses with insulin resistance used to be incorrectly categorized as “hypothyroid.” Further research has shown that very few horses are actually hypothyroid, however many horses with insulin resistance can have low measurable levels of thyroid hormone. However their thyroid glands are working fine, and the insulin resistance is the main issue. In spite of this, supplementing with thyroid hormone can help boost the metabolism and get a horse to start losing weight. The thyroid hormone may be given once daily for a couple of months and then tapered down and discontinued.
A drug used in humans to treat insulin resistance, called “metformin,” shows promise in treatment of equine insulin resistance. However at this time it has not yet gained wide usage for horses, as safety and efficacy studies are just being performed. Additionally, most horses, unless they have severe chronic insulin resistance, respond fairly well to dietary and exercise changes and do not need medication.
Also, just as with equine Cushing’s disease, there are many herbal supplements advocated to treat equine metabolic syndrome. Again there is little proof of efficacy or safety of these treatments.
If you are concerned that your horse has signs of either metabolic syndrome or equine Cushing’s disease, set up an appointment with your veterinarian for an examination and discussion. It is not always easy to distinguish between these two conditions, but recognition is important to provide your horse with the best care.