Cushing’s Disease

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Introduction: Cushing’s disease is a slowly progressive condition that is a result of abnormally high levels of cortisol in the body. Although the disease can occur in any breed of horse, it is more common in Morgans and some pony breeds. It can occur in horses of both sexes and in animals of all ages; however, it seems to be more common in older animals. Although a relatively rare disease when compared to other horse diseases, Cushing's disease is showing up more often. One reason for this is because horses, like humans, are living longer due to advances in health care and nutrition. Cushing's disease can be found in humans, dogs, horses and other mammals. This disease is also known as pituitary pars intermedia dysfunction (PPID), hyperadrenocorticism, equine Cushing's disease (ECD) and Cushing's syndrome. Metabolic syndrome, also known as peripheral Cushing's syndrome, is a different ailment that has many of the same symptoms of Cushing's disease. Clinicians say it could be a factor in horses that develop Cushing's disease.

Anatomy: The pituitary is a small gland located near the base of the brain. It regulates almost all of the body's endocrine (hormonal) systems. It is often called the "master gland." The hypothalamus, located near the pituitary, works in conjunction with the pituitary gland to regulate the body's systems. Hormones produced by the pituitary and hypothalamus influence the adrenal glands to produce or not produce cortisol.

Cortisol is a steroid hormone produced by the body’s paired adrenal glands, specifically by the gland’s cortex or outer layer. The adrenal glands in horses with Cushing’s disease have, for one reason or another, a broken "off switch" and produce too much cortisol. Excess cortisol results in many different problems throughout the horse’s body. The following list contains some of the normal functions of cortisol in the body:

Causative Agents: Over the years, most clinicians agreed that this disease is caused by a benign tumor (adenoma) of the pituitary gland. The pituitary gland normally stimulates the adrenal gland to produce cortisol. When the pituitary gland has a tumor, it over-stimulates the adrenal gland and excessive amounts of cortisol are produced. Recently, other possible causes of Cushing’s disease have been determined. One problem occurs when there is a breakdown (degeneration) of the hypothalamic dopaminergic neurons in the hypothalamus. This problem is called pituitary pars intermedia dysfunction (PPID) and is considered by some to be the most common cause of equine Cushing’s.

Peripheral Cushing’s syndrome or metabolic syndrome is another potential cause that some scientists believe could be a cause of Cushing's disease. In these cases, it is thought that changes in the brain which affect the pituitary gland are responsible for the development of the disease, instead of a tumor.

Clinical Signs: Polydipsia (excessive thirst) and polyuria (excessive urination) are the first symptoms often noticed. Normal horses often drink from 6-10 gallons of water per day. A Cushing's affected horse might go through as much as 21 gallons of water a day. Because of muscle weakness and atrophy (shrinking), Cushing's disease also causes a swaybacked or potbellied appearance and a loss of muscle over the top line. The horse may experience an increased appetite without the corresponding weight gain. A history of chronic laminitis, often without any known cause, is a common sign.

Another common sign that may be noticed by an owner is a change in the horse's coat. It fails to shed in the summer and becomes heavy, coarse, and wavy. Since cortisol regulates the immune system, a horse with Cushing's disease often suffers bouts of respiratory disease, skin infections, parasite infections, foot abscesses, mouth ulcers, and periodontal or dental disease. Wounds tend to heal slowly. Occasionally, a mare's estrous cycle will be abnormal or not occur at all. Some horses with Cushing's disease have become completely sterile. Mares may even produce milk despite not being pregnant. Having a horse that is lethargic and lacks energy is another sign of Cushing's disease.

When a tumor is involved, it can swell and eventually put pressure on the hypothalamus and surrounding structures. The optic nerve is also nearby, and large tumors have been found to have put enough pressure on that nerve to cause blindness. Head tilting and dementia have also been the result of the larger tumors.

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Diagnosis: Blood tests can reveal high blood sugar levels, high blood fats, anemia, reduced lymphocyte counts, and electrolyte imbalances. A CBC (complete blood count) will reveal if the horse is suffering from hyperglycemia (high blood sugar), which is often present in animals with Cushing's disease due to insulin resistance. The blood sugar levels of affected horses are over 120 mg per dl; sometimes they rise to over 300 mg per dl. A urinalysis can detect glucosuria and ketonuria (abnormally high levels of glucose and ketones in urine) and may prompt more specific hormone-related tests.

When additional testing is done, the dexamethasone suppression test (DST) is commonly run. First, a blood sample is taken to establish a baseline on cortisol levels. Then, dexamethasone is administered and another blood test taken in 19-24 hours. Cortisol levels are normally elevated in horses with Cushing's disease.

The ACTH stimulation test is another way of measuring cortisol levels in the blood. One unit of ACTH gel is given per kg of body weight. Cortisol levels are then measured 4 to 8 hours later. A diseased horse will show a four-fold rise in cortisol, whereas a normal horse will only show a two to three fold increase. However, it is important to note that recent research has cast a shadow on the accuracy of these tests, since there is such a wide range of "normal" hormone levels in horses. Furthermore, simply being off feed can throw hormone levels off by as much as 50 percent in some tests.

Recently, other tests have been developed. One test combines the dexamethasone suppression test with a thyrotropin releasing hormone (TRH) stimulation test which results in a "spike" in cortisol levels. By measuring blood cortisol levels 3 hours after injecting dexamethasone and immediately following it with an injection of TRH, one can measure elevated cortisol levels just 30-45 minutes later. Another test measures pituitary peptides. It is supposedly very safe and avoids the use of dexamethasone (which may produce laminitis).

Treatment: If caught early, Cushing's disease is very treatable and the horse can enjoy several years of health. Horses with advanced cases of the disease are usually suffering symptoms from secondary afflictions and are harder to treat. It is important to also realize that the pituitary gland is inaccessible, so removing any tumor is not an option.

Currently, two medications are often used to treat Cushing’s disease. One that seems to work the best is pergolide mesylate (Permax). Pergolide is a dopamine agonist originally used to treat Parkinson's disease in humans. At small dosages, smaller even that those used in humans, this drug can help without the high risk of laminitis that has formerly been connected to its use.

The second drug that is sometimes used is Cyproheptadine. Cyproheptadine is a serotonin blocker that can be administered using a lower dose at first, with gradual increases until symptoms begin to improve. A simple way to determine improvement is monitoring the polyuria and polydipsia of the horse. As soon as the horse's drinking returns to normal levels, the dosage is at the right level for that horse. At that point, the other symptoms of Cushing’s disease have usually stopped as well. After a month of improvement, the dosage can be decreased slowly until it is at a maintenance level. Most horses with Cushing's are on medication for the rest of their lives.

In addition to medication, horses with Cushing's disease need careful management of their health. A proper diet, vaccinations, deworming and dental care are important due to the cortisol’s ability to suppress the horse's immune system. They may also need special help in maintaining proper hoof health and body temperature, since laminitis and faulty thermoregulation are symptoms of Cushing's disease.

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