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Equine Cushing's disease or syndrome is the most common disease in horses and ponies aged 15 years and older. Equine Cushing's disease is also know as pituitary pars intermedia dysfunction (PPID). In horses, as opposed to dogs, Cushing's disease is solely a disease of the pituitary gland. The pituitary gland lies at the base of the brain and has a number of roles with regards to hormonal production and regulation. The pituitary gland in the horse has 3 distinct lobes: pars nervosa, pars intermedia and pars distalis, each with a specific role with regards to hormonal regulation. The pars intermedia produces a protein called pro-opiomelanocortin (POMC) that is converted to adrenocorticotropin hormone (ACTH). This hormone is in turn processed into several other hormones: - alpha melanocyte stimulating hormone (alpha MSH), an anti-inflammatory hormone that has a role in skin pigmentation, appetite and lipid metabolism
- beta-endorphin, an endogenous (body produced) opioid with roles in analgesia, behavior, immune responsiveness and blood vessel tone
- corticotrophine-like intermediate lobe peptide (CLIP), stimulating insulin release
Horses and ponies affected with PPID have a benign tumor of the pars intermedia portion of the pituitary gland. This tumor rarely may result in a sudden onset of acute neurological disease, most likely due to the size of the tumor. In the majority of horses, PPID signifies the presence of this benign tumor. Chronic production of ACTH affects the secretion of cortisol by the adrenal glands, causing this to be overproduced as well. Overproduction of cortisol affects the immune system and water balance in the body. Season has been found to play a large role in hormone production and can confound diagnostics. Alpha-MSH levels are highest in the fall, which has been theorized to play a role in preparing the body for upcoming winter. Dysregulation of this pathway in horses with PPID may be associated with changes in body weight and fat storage. This may explain why early signs of PPID include a heavy haircoat or reduced shedding/prolonged shedding in horses and ponies. Other signs may include recurrent, intermittent laminitis, recurrent solar abscesses, fat deposition in the supraorbital fossa (depression above the eyes), development of a cresty neck, chronic infections such as tooth root abscesses, increased thirst and urination. As stated above, diagnostics can be confounding depending on the season of the year. The gold standard is currently the dexamethasone suppression test. This test requires the administration of a dose of dexamethasone after collecting a serum sample at 5 pm, then repeating the serum sample between 8 am and 12 pm the following day. In normal horses, dexamethasone administration suppresses the production of cortisol. In horses with PPID, administration of dexamethasone may not suppress cortisol production. Some clinicians are reluctant to administer dexamethasone to horses with a history of laminitis. Additional diagnostic methods include measuring serum cortisol levels, endogenous ACTH levels and insulin levels. These tests are less conclusive, particularly if performed during the fall. A new method of diagnosing PPID involves the administration of domperidone by mouth and testing the levels of ACTH. Domperidone, used most commonly for treating fescue toxicosis in pregnant mares, is a dopamine receptor antagonist that exacerbates the loss of dopaminergic inhibition in horses with ACTH, resulting in elevated levels of endogenous ACTH. Management of horses and ponies with PPID involves clipping the hair coat in the summer if the horse or pony does not shed out completely, addressing the laminitis appropriately, providing good preventative care and performing routine blood work to ensure organ systems remain functional, providing a balanced and easily digestible diet, performing routine dental floats and ensuring routine visits by the farrier. Therapy is available in the form of pergolide or cyproheptadine. This treatment is aimed at reducing the clinical signs of PPID. There is no permanent therapy in terms of tumor removal due to the location of the pituitary gland. Pergolide binds to dopamine receptors in the pituitary and reduces secretion of ACTH. Pergolide is the drug of choice for treating PPID. Horses that respond to pergolide usually have resolution of clinical signs of PPID. Cyproheptadine is less effective and works by binding to serotonin, leading to a decrease of alpha-MSH.
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