PITUITARY PARS INTERMEDIA DYSFUNCTION (PPID, EQUINE CUSHING'S DISEASE)
ETIOLOGY Also known as Equine Cushing’s Disease, Pituitary Pars Intermedia Dysfunction (PPID) is a dysfunction of the pituitary gland. This disease is most common in horses over 10 years of age. The pituitary gland, located at the base of the brain, becomes hyperactive and releases an excess of adrenocorticotropic hormone (ACTH) into the horse’s bloodstream. Excess ACTH signals the adrenal glands (located near the kidneys) to produce an excess of cortisol, a hormone with wide-ranging effects all over the body. These hormonal changes may result in the clinical signs listed below. It is important to remember that early cases may occur without any visible signs.
- A long, thick, and curly hair coat that does not shed well in the spring
- Loss of muscle, especially along the top line
- Weight loss
- Increased water consumption and urination
- Infertility or abnormal heat cycles (mare)
- Insulin dysregulation
- Immunosuppression and chronic infections
Diagnosis of PPID is based on the horse’s history, clinical signs, and laboratory blood testing. The baseline ACTH test alone (see below) often results in false negatives in cases of early PPID. The most sensitive test we have for detecting early PPID is the TRH stimulation test.
TRH STIMULATION TEST
The TRH stimulation test requires that a small dose of TRH (thyrotropin releasing hormone) be administered intravenously. A blood sample is drawn 10 minutes later. This test is considered positive for PPID if there is an abnormally high level of ACTH in the blood sample. Horses without PPID may have elevated TRH stimulation test results in the fall months. Because we do not yet have laboratory reference ranges for this test’s results between mid-July and mid-November, we do not recommend using this test during that time period. If you would like us to test your horse for PPID during those months, we could use a less sensitive test, the ACTH baseline (see below). If the test results are negative for PPID, then we would recommend doing a TRH stimulation test after mid-November. Horses should not have a grain meal within 12 hours before having a TRH stimulation test.
This test can still be reliable for detecting and monitoring more advanced cases of PPID. There are different reference ranges for ACTH levels in the fall compared with during the rest of the year. All horses, including those with PPID, have an increase in baseline ACTH in the fall as their bodies prepare for winter, but those with PPID will have a more dramatic increase. We use this test primarily to monitor response to treatment in horses who were initially diagnosed with an ACTH baseline before the TRH stimulation test was available. We also may use this test in the fall months when the TRH stimulation test is not recommended.
The hormonal changes present in PPID can result in insulin dysregulation (ID). The horse’s pancreas makes insulin in response to rising blood glucose after the horse eats a meal. Insulin helps glucose be distributed throughout the various tissues in the body. With ID, the body does not respond normally to insulin and the pancreas produces more and more to try to compensate. High blood insulin (hyperinsulinemia) is a major risk factor for laminitis. This is a significant reason why horses with PPID are at increased risk of laminitis. We recommend testing insulin in all horses diagnosed with PPID to see if ID is a problem and to thus get an idea of laminitis risk.
Like with PPID testing, there are multiple tests for insulin. While a baseline insulin test only requires fasting from grain for four hours and one blood draw, it has a high rate of false negatives (nondiagnostic results). Even horses with ID may often have normal baseline insulin levels. However, if baseline insulin is high, then ID has been diagnosed. If baseline insulin is normal (and possibly a false negative) or if you would like to start with a more sensitive test, the Oral Sugar Test (OST) is most useful. This entails fasting the horse from all food for three to 12 hours, then giving corn syrup orally, and then having blood drawn 60 and 90 minutes later. This test detects insulin response after an influx of sugar in the gastrointestinal tract and is more likely to identify horses with ID compared with a baseline insulin test. The OST does not induce laminitis or cause any long-term negative health effects.
We may also choose to measure blood glucose during insulin testing to check for diabetes mellitus (shown by uncontrolled high blood glucose), which is uncommon in horses.
ID can be managed with diet, exercise, and medications (see Equine Metabolic Syndrome information).
PPID is best treated with a medication known as pergolide. The only available FDA-approved pergolide product is called Prascend and is made by Boehringer-Ingelheim. There are less expensive, compounded formulations that may be effective, but research has demonstrated that there may be concerns about concentration and stability in compounded formulations of pergolide. Prascend is available in a tablet form that is given once daily orally. You should not crush the tablet—this presents human health risks. Prascend is considered generally very safe, but some horses will have a decreased appetite when the medication is started. We recommend repeating a diagnostic blood test 30 days after starting pergolide to ensure the dose is adequate. We also recommend annual retesting to continue monitoring response to treatment; PPID tends to progress over time and the dose of pergolide may need to be increased. Cyproheptadine is an adjunct medication that may be used in cases of PPID that do not respond well even to high doses of pergolide.
Supportive therapy for horses with PPID includes clipping abnormally long coats in the summer to prevent overheating, close monitoring for signs of laminitis, and careful diet and weight management.