Equine pituitary pars intermedia dysfunction (PPID) or equine Cushing's disease is caused by an enlargement of the pars intermedia of the pituitary gland, resulting in overproduction of the steroid cortisol and loss of the normal feedback mechanisms that affect cortisol production. The pars intermedia is the central part of the pituitary gland situated at the base of the brain and is involved in the metabolism of cortisol and endorphins (hormones that relieve pain).
Cortisol is released by the adrenal glands in response to a complicated cascade of hormone interactions that begin in the hypothalamus and pituitary gland. Although it is commonly thought that a tumor causes PPID, it is actually an enlargement of the pars intermedia that occurs due to a lack of response to the neurotransmitter dopamine. In normal horses, dopamine and increased blood concentrations of cortisol signal the pars intermedia to reduce cortisol production.
PPID is a condition of mature to older horses and has been reported in horses as young as 7 years old. Many aged horses, perhaps all, have some degree of enlargement of the pars intermedia of the pituitary gland. However, not all horses will show significant clinical signs or require treatment.
Clinical signs of PPID include shaggy hair that does not shed in summer, weight loss, laminitis, increased susceptibility to infections, and excessive water intake and urination. Interestingly, some studies have found that a long winter coat that does not shed in summer in older horses is just as reliable as an indicator of PPID as any laboratory test.
The endocrine system produces hormones that are circulated throughout the body in the bloodstream. Most hormones have a complex cycle that regulates their activity, and many hormones affect the actions of others. The most important warning that a veterinarian can give the horse owner is to be prepared for some abnormal results, even in normal horses, when performing endocrine testing. The concentration of one or more hormones very likely will be out of the normal range. The difficulty in interpreting endocrine tests lies in determining what abnormalities are significant and if some other factor (insulin resistance, drug administration, etc.) is influencing the hormone.
Tests for PPID can include the following:
Dexamethasone suppression test: Blood cortisol is measured before and 19 hours after injection of the steroid dexamethasone. The steroid is usually injected in the muscle between 4 and 6 p.m. and cortisol is measured again the following morning. A normal horse should respond with a very low blood cortisol concentration after injection of dexamethasone. This is due to negative feedback whereby high circulating levels of steroids (from the dexamethasone) signal the body to suppress the release of cortisol. Horses with PPID lack this normal response and will continue to have normal to elevated cortisol concentrations (failure to suppress). This test remains the gold standard for PPID diagnosis. There is a slightly increased chance for exacerbating any laminitis that may be present with dexamethasone administration, but this risk is relatively small and most clinicians consider it to be a safe test unless obvious laminitis is present. Results of dexamethasone suppression tests are not reliable if the test is performed during the fall and early winter because cortisol concentrations are higher during that part of the year.
Adrenocorticotropic hormone (ACTH): ACTH is produced by the pars intermedia of the pituitary gland and signals the adrenal glands to produce cortisol. ACTH may not be elevated in all horses with PPID, but consistently elevated concentrations probably confirm PPID. Storage and collection of serum for ACTH can be difficult because the hormone is not stable under normal conditions. Assay of ACTH is not reliable during the fall, as its concentration is normally increased during that time of year.
Thyrotropin-releasing hormone (TRH) stimulation test: Some cells in the pars intermedia of the pituitary gland release ACTH in response to TRH administration, and this will result in increased blood concentrations of cortisol. Unfortunately, the test is infrequently performed and TRH produced specifically for equine diagnostic testing is unavailable, but TRH can be purchased from chemical suppliers.
Domperidone response test: This is a relatively new diagnostic test for PPID. Domperidone (EquidoneÂ®) is most commonly used for the treatment of decreased milk production and tall fescue toxicosis. Domperidone inhibits dopamine, which allows the pituitary gland in horses with PPID to release even more ACTH. Horses with PPID will double their ACTH concentration 4-8 hours after domperidone administration, while normal horses will maintain normal concentrations of ACTH. As more horses are tested using the domperidone response test, its clinical value will become better known.
Glucose and insulin concentrations: Insulin resistance is fairly common with PPID. Elevated cortisol antagonizes the actions of insulin, and if insulin resistance is present, then blood concentrations of glucose and insulin will be increased. Several other conditions can also cause insulin resistance; therefore diagnosis of insulin resistance is a symptom rather than a confirmation of PPID.
The "big picture" of the horse's laboratory results, clinical signs, history, and other coexisting conditions determines which, if any, endocrine abnormalities need to be addressed. Many, if not most, older horses have PPID. Horses that are not showing any adverse clinical signs of PPID usually do not need to be treated; however, if the horse is having chronic laminitis, weight loss, or recurrent infections, then treatment is likely to be beneficial.--Dr. Bryan Waldridge
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