Cushing’s Disease in Horses and How Equine Cushing Disease Can Benefit From Genetics Research.
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What is Cushing’s Disease in Horses?

written by: dgemmellaro•edited by: Paul Arnold•updated: 8/31/2009

Due to the common ancestry of all species, many diseases, (especially genetic) found in humans can be found in other organisms. For example, Cushing’s disease, an endocrine disease that affects people, can also be found in a variety of other animals, including horses.

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    Cushing’s disease in horses, though similar in name to Cushing’s disease in dogs and humans (and that found in a variety of other animals species), is most often the result of endogenous (within-the-body) factors, all relating to the horse’s pituitary gland. Specifically, many causes of Cushing’s disease in horses are the result of problems within a particular area of the pituitary gland, known as the pars intermedia (which literally means "the intermediate part").

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    Causes of Equine Cushing's Disease

    Often, the disease, known by a variety of names including Equine Pituitary Gland Hyperplasia (EPGH), as well as Pituitary Pars Intermedia Dysfunction (PPID), results either from an adenoma (a benign tumor) or a benign hypertrophy (increase in cell size) in the pars intermedia. Whatever the reason, the pituitary gland increases in size and in some cases becomes so large as to actually press against other areas of the brain. This can lead to neurological problems and some horses have been known to suffer blindness or seizures.

    Besides causing neurological problems (which often do not occur), the dysfunctional pituitary also has an effect on the adrenal glands, which are continuously stimulated to produce cortisol. The pituitary gland is an important organ in the endocrine system, which releases chemical signals to instruct various other organs in the body. These signals can take the form of hormones or proopiomelanocortin peptides (POMCs). In equine Cushing’s disease, the pituitary tumor causes the gland to remain active continuously and secrete POMCs non-stop.

    In other cases, there is no cancerous growth within the pituitary gland. Instead, some scientists have found that there is a connection between dopamine production and equine Cushing’s disease, as well as abnormal enzyme activity and the disease. It is known that the pars intermedia is tightly governed by neurotransmitters, mainly dopamine, secreted by the hypothalamus. Dopamine inhibits the activity of the pars intermedia. Horses with Cushing’s disease seem to have dopamine-producing nerve cells that are “weak", or that seem to die easily. Studies are now being done as to why these cells are so prone to dying. The abnormal enzyme linked to the disease is 11-beta hydroxysteroid (HSD), which is found within cells and is responsible for making sure the concentration of cortisol remains within an acceptable range.

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    Symptoms and Diagnosis of Cushing's Disease in Horses

    There are a number of ways of seeing if a horse is affected with equine Cushing’s disease. Affected horses:

    • often grow long wavy coats throughout the year;
    • are very skinny;
    • are lethargic;
    • often have “pot bellies" because of weak abdominal muscles;
    • often sweat profusely;
    • breathe heavily;
    • sometimes cannot stand;
    • often present laminitis, a painful inflammation of certain structures in the hoof; if left untreated, a horse suffering from laminitis could go lame;
    • drink copiously;
    • urinate frequently;
    • are incredibly susceptible to infections, given the fact that the increased cortisol in the blood has an adverse effect on immune functioning.

    Diagnosing the disease in horses is similar to diagnosing it in dogs. The most common test is the dexamethasone suppression test, followed by the evaluation of ACTH levels in the body. Some veterinarians recommend testing for cortisol levels or testing for high insulin levels, thought to be associated with Cushing’s disease in horses and other animals. All of these screens have their drawbacks and new tests are being developed; one that seems promising is a test for thyrotropin-releasing hormone.

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    Treatment and Genetic Research

    There is no cure for equine Cushing’s disease, though there are treatments that can prolong the life of a horse for at least 5-7 years. The drug that is most commonly used is Pergolide mesylate, which is actually a drug to treat Parkinson’s disease in humans. The drug works by causing the release of dopamine, which, as we learned earlier, is essential in curbing the activity of the pituitary gland. Trilostane, another human drug, works instead on the adrenal glands, curtailing the production of cortisol. Dietary management is also suggested.

    Genetic research can be very beneficial to an increased understanding of equine Cushing’s disease. Preliminary studies suggest that Morgan horses and ponies are more susceptible to the disease, and so further testing is needed to see if Cushing’s is an inherited disorder in these groups. Once the pattern of transmission is known, breeders can be more careful in setting up matings, so as to minimize the incidence of the disease in equine populations. Furthermore, knockout mice models, as well as knock in models, are helping scientists understand the underlying causes of this disease.

    For example, scientists are looking at gain of function mutations in a transcription factor for the expression of a POMC in dogs to ascertain whether this type of mutation could lead to Cushing’s-type symptoms in other animals. They are also creating knockout mice that have a mutation inhibiting expression of receptors in their pars intermedia cells responsible for responding to dopamine. Differential gene expression studies have found a tentative, preliminary link between Bone Morphogenetic protein-4 (BMP-4) and pituitary tumors. Other genes are being studied as well.

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    Millington, WR et al. "Equine Cushing's disease: differential regulation of beta-endorphin processing in tumors of the intermediate pituitary." Endocrinology. 1988.

    Geor, R. "Cushing's Disease and Other Problems of the Older Horse." R and J Veterinary Consultants.

    TheHorse.Com. "Equine Cushing's."

    McFarlane, D et al. "The Role of Dopaminergic Neurodegeneration in Equine Pituitary Pars Intermedia Dysfunction (Equine Cushing's Disease). American Association of Equine Practitioners. 2003.

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