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Cushing’s Disease – A Review

 Cushing’s Disease is a common disease in the aged horse.  Another term for Cushing’s Disease is Pituitary Pars Intermedia Dysfunction (PPID).  This syndrome is a disruption to the endocrine (hormone) regulation in the horse.  Specifically the syndrome disrupts the normal metabolism of dopamine, a hormone, at the level of the brain.

Affected horses are typically greater than 15 years old, and there is no sex predilection.  All breeds can develop the disease but ponies and Morgans have a higher incidence.  Common clinical signs include muscle wasting, hirsutism (abnormally long hair coat that does not shed out properly), obesity with fat redistribution along the horse’s top line, bulging fat pads over the eyes, cresty neck and increased appetite. Some affected horses become more docile.  In addition,  recurrent infections, episodes of laminitis, and increased drinking and urination may be observed.  Not all horses with Cushing’s disease exhibit all of these clinical signs, but they may have a combination of some of the signs.

Normal horses produce Dopamine in the brain at the level of the hypothalamus by neuronal (nerves) stimulation.  Dopamine travels to the pituitary in the brain through these neurons from the hypothalamus to regulate the production of a number of hormones.  Melanocytes in the pars intermedia in the pituitary produce POMC, the precursor to ACTH, alpha MSH and beta endorphin.   Dopamine has negative feedback on the production of ACTH in the pars intermedia. 

Horses with PPID may have a decreased production of dopamine by the nerves in the hypothalamus, or have decreased ability to receive dopamine at the level of the pituitary in the brain.  The exact cause of neuron degeneration of the hypothalamus dopaminergic neurons is unknown.  This decrease in dopamine concentration or action at the pituitary in turn allows for an over production of adrenocorticotropic hormone (ACTH) by the pituitary.  This in turn produces pituitary hyperplasia.  ACTH then travels through the blood stream to the adrenal glands and stimulates an increase in steroid production (cortisol and dexamethasone) by the adrenal glands.  This increase in steroid production is responsible for the majority of the clinical signs seen in horses with Cushing’s Disease. 

Click here for diagram of ACTH production

Numerous tests have been used to diagnose the disorder.  This is because there is no single perfect test to diagnose PPID.  One of the more common, relatively noninvasive and easier tests to perform is to measure ACTH levels in the blood.  This simply requires your veterinarian to obtain a blood sample and send it to a lab that is able to perform this test.   It was once thought that the fall was not a good time of year to test horses with suspected Cushing’s disease, as it was believed that false positives were more likely to occur during this period.  Research on the disease has now given us more accurate normal levels of ACTH during different periods of the year. 

Other recommended tests:

TRH stimulation test

Available tests with lower recommendations:

Dexamethasone suppression test 

Measurement of alph MSH, more stable than ACTH, but no commercial tests available currently

Measurement of resting cortisol – frequently normal

ACTH suppression test

If clinical signs and diagnostic testing are suggestive of a diagnosis of Cushing’s Disease, treatment may be indicated.  One of the most commonly used drugs to treat horses with Cushing’s disease is called Pergolide.   This drug is a dopamine agonist, and inhibits production of POMC in the pars intermedia.  Remember that dopamine decreases the production of ACTH at the level of the pituitary in the brain, which is helpful in horses with Cushing’s disease, because their ACTH level is too high.   Pergolide is one of the drugs used to treat Parkinson’s disease in humans.  This disease is also characterized by low levels of dopamine.  Pergolide is safe and is given orally to horses once a day.  The treatment is typically lifelong due to the fact that the condition is irreversible. 

Cyproheptadine – serotonin antagonist inhibits secretion of ACTH.  Not as affective at lowering ACTH levels as Pergolide.  Can combine with pergolide.

Trilostane – competitive inhibitor of 3beta-hydroxysteroid dehydrogenase, used in clinical trials, decreased PU/PD and improved laminitis in some horses

Chasteberry – herbal dopamine agonist

Environmental and health care changes must be implemented as well.  Dietary modifications are very important in horses with Cushing’s disease.  Horses should be fed decreased amounts of carbohydrates and easily digestible sugars.  Many of the feed companies have well balanced diets designed specifically for this purpose.  In addition affected horses should have limited access to green grass, concentrates (grains) high in carbohydrates, and treats (apples and carrots).  Dirt paddocks are ideal as they allow affected horses to get outside, yet not ingest all the carbohydrates from the green grass.  Grazing muzzles are also useful if no dirt paddocks are available.  The grazing muzzle decreases the rate at which the horse ingests green grass, yet makes it possible for the horse to be outside.  Horses diagnosed with Cushing’s disease may be susceptible to laminitis as well.  Regular monitoring of feet with a routine trimming schedule is paramount.  Good dental care is also important and horses should have their teeth floated regularly.     

It is vital to perform good husbandry practices for horses diagnosed with Cushing’s disease in order to extend good quality of life.  A sound preventative veterinary care program is a key feature and must pay special attention to their diet, deworming program, dental and hoof care.