Pituitary pars intermedia dysfunction (PPID, equine Cushing’s disease) is an age-related endocrine disorder that occurs in about 20% of horses, ponies, and donkeys 15 years of age or older. PPID can occur in younger horses, but it is rare in those younger than 10 years of age. At this time, age is the only significant risk factor for PPID; no breed or sex predispositions have been determined.
The pituitary gland, located at the base of the brain, has an important role in regulating body hormones. These hormones affect many metabolic and reproductive functions, blood pressure, and electrolyte balance. Horses with PPID develop enlargement and benign tumors in the pars intermedia, or the middle lobe, of the pituitary gland. This condition affects hormone production pathways in the brain, specifically from the hypothalamus and pituitary gland. The release of hormones from the pituitary gland is normally controlled through the neurotransmitter dopamine from the hypothalamus. In horses suffering from PPID, degeneration of the neurons that produce dopamine results in oversupply of hormones produced by the pars intermedia, and the subsequent high levels of these hormones can affect various body processes.
Approximately 30% of horses diagnosed with PPID also exhibit abnormal glucose metabolism (insulin dysregulation), in which blood insulin levels are high due to decreased insulin response in tissues. Insulin dysregulation places horses with PPID at higher risk of developing laminitis, which is one of the most serious complications of PPID. Insulin dysregulation is the defining characteristic of equine metabolic syndrome (EMS), and PPID and EMS can occur simultaneously in a horse. Horses with EMS may be at higher risk of developing PPID as they age, and at this time it is not known whether EMS and PPID are causatively linked.
The most common clinical signs of PPID include an abnormal haircoat (regional patches of long hair such as legs, chin, and belly), failure to shed (hypertrichosis), muscle loss, lethargy, chronic infections, weight loss (profound loss of fat and muscle), potbelly due to lost muscle tone, and abnormal sweating, either increased sweating (hyperhidrosis) or lack of sweating (anhidrosis).
Early diagnosis of PPID can be difficult. Blood tests are often negative in early stages of PPID, and symptoms can be overlooked in the normal aging process. Clinical signs of PPID may lead to a diagnosis based on examination and history. The long haircoat typical of PPID horses is often used as a diagnostic tool, but should not be used as an absolute diagnosis since malnutrition and other conditions can cause haircoat changes. Horses with mild PPID may be at risk of laminitis, so screening tests are important to help identify horses with PPID before overall health declines or laminitis develops.
Measurement of baseline ACTH is often used in diagnosis of PPID. Horses with more advanced PPID often exhibit elevated levels of ACTH, so resting plasma ACTH concentration is typically measured and compared to a reference range. However, ACTH levels can be affected by season, stress, illness, exercise, and sometimes diet, so testing the horse in its home environment when healthy and not stressed will yield the best results. A baseline ACTH test is most helpful for detecting moderate to advanced cases of PPID but may not detect early stage PPID.
Additional testing, such as thyrotropin releasing hormone (TRH) stimulation test, may provide additional evidence of early stage PPID, or when ACTH testing is inconclusive. In this protocol, after a baseline ACTH sample is collected, TRH is administered intravenously and in 10 minutes an additional ACTH sample is collected. However, there can be substantial variability in the results.
Because many PPID horses exhibit insulin dysregulation, and PPID and EMS can coexist, testing for insulin dysregulation is also important when PPID is suspected.
PPID is a progressive condition, and there is no cure. Treatment is intended to address and reduce clinical signs of the disease and must be continued for the life of the horse. The prognosis for horses diagnosed with PPID is variable and somewhat dependent on symptoms. Some horses respond to a low level of medication, while others require a much higher level. Some horses respond well to management protocols and may not require medication to maintain quality of life.
The only medication licensed for treatment of PPID in horses is pergolide mesylate. Pergolide is a drug that acts on receptors within the pars intermedia to suppress tissue enlargement and tumor growth. Amount of pergolide that results in improvement of clinical signs can vary, and horses that do not respond to high doses of pergolide may be treated with additional medication as prescribed by the veterinarian. Ongoing monitoring of horses undergoing treatment is important, and it is recommended that retesting be performed at least twice a year to determine if changes in medication are needed.
Diet and exercise can help manage some symptoms of PPID but is not a cure. The horse’s body weight and condition, ability to exercise, and presence of insulin dysregulation will influence management recommendations. Further, the horse’s age will affect dietary requirements. Because PPID is a disease of aged horses, in many cases the horse’s dental condition will determine appropriate dietary changes. If the horse is suffering from poor dentition (missing teeth, lack of chewing surface for utilization of long-stemmed forages), a ration that provides forage alternatives such as pelleted forages or a formulated senior feed with adequate fiber to replace hay and pasture may be required to help support the older horse’s needs.
There are no specific dietary guidelines for PPID horses because symptoms vary. Not all PPID horses are prone to laminitis, so that must be taken into consideration. Some PPID horses are hard keepers and some are easy keepers, so it is important to feed appropriate calories to maintain body weight and condition. If the horse is at risk of laminitis, maintaining appropriate body weight is essential to ensure that excess weight is not putting strain on compromised hooves. Further, providing a diet with controlled soluble carbohydrates to avoid blood glucose/insulin response that may increase risk of laminitis is an important part of dietary management. If the horse is a hard keeper and at risk of laminitis, a higher calorie diet is recommended, but soluble carbohydrate levels are still of concern. Higher fat content to replace some soluble carbohydrates in the diet may be helpful in providing calories to support body weight and condition without increasing risk of laminitis.
If the PPID horse is not exhibiting insulin dysregulation, soluble carbohydrate content of the diet is not as much of a concern. As the disease progresses, though, it is important to monitor this and make changes if necessary.
Adequate high-quality protein in the diet of PPID horses may help reduce muscle wasting, as well as support muscle maintenance and repair. Appropriate vitamin and mineral supplementation is also vital to support the aging horse’s nutrient requirements and potentially compromised immune function. While many supplements are marketed to specifically address the needs of PPID horses, at this time there is little published data to support specific ingredients or additives to address the symptoms of PPID.
