MBH Research. PPID in Horses

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Jason Hicks
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Latest in Equine Science MBH Research By Joan Kulifay, MSc, BS PPID in Horses What is PPID? Pituitary Pars Intermedia Dysfunction (PPID) is a common endocrinopathy diagnosed in horses.

Newer research has shown that this starts long before the coat issues show up and is found in many horses without coat issues. PPID is a hyperplasia or adenoma of the pituitary gland.

1 Latest in Equine Science MBH Research By Joan Kulifay, MSc, BS PPID in Horses What is PPID? Pituitary Pars Intermedia Dysfunction (PPID) is a common endocrinopathy diagnosed in horses. Previously, it had been called Cushing s Disease, with the hallmark characterization of a long, wavy coat. Newer research has shown that this starts long before the coat issues show up and is found in many horses without coat issues. PPID is a hyperplasia or adenoma of the pituitary gland. This is where a small group of cells become more active and create a tiny tumor within the gland. We call a small tumor a hyperplasia, while a large one is termed an adenoma. Why Should We Be Concerned About PPID? PPID occurs mostly in older horses and is treatable. At one point in time, a diagnosis of Cushing s Disease was considered a death sentence. We now have a better understanding of the degenerative process and can effectively treat it. There is no need for our horses to suffer from untreated or undertreated PPID. What Are The Symptoms of This Disorder? The first symptom most commonly seen in PPID is unexplained fall laminitis. Other symptoms include loss of muscling along the topline, eye tearing and lethargy. Additional symptoms may include increased drinking and urination. A long wavy coat is also seen. Coat changes usually occur when this disorder has progressed for quite some time. PPID also causes changes to the immune system, allowing the horse to be more susceptible to infections. Insulin resistance may also be present in these cases. This is different from PPID, but was originally termed peripheral Cushing s. It is not the same, but is sometimes confused by vets because some of the symptoms overlap. It can be distinguished from insulin resistance by blood testing. Diagnosis: One of the difficulties that we have is that our testing methodology is not entirely accurate. Many horses in the early stages of PPID will test as being normal. They have the start of the degenerative process, but it is still too early to show up on testing. One of the questions that researchers ask is if they can come up with a better test than the tests currently in use.

2 Page 2 How is PPID Currently Diagnosed? A very safe and commonly used test for PPID is the endogenous ACTH test from a laboratory like Cornell. This is a single blood draw into a purple topped tube (EDTA), spun and cell separated within four hours, then frozen and shipped. This is easy on the horse, but requires that your vet has a mobile centrifuge or can get back to the office to have it spun down before the sample starts to decay. What Are Alternatives To This Method of Diagnosis? An alternative test to the endogenous ACTH test is the dexamethasone suppression test. This is a test where the vet draws a blood sample in the early evening, then injects the horse with a steroid (dexamethasone). The vet returns around noon the next day and pulls another blood sample. The test is considered positive if the dexamethasone fails to suppress the ACTH by the second draw. This used to be the most popular method of diagnosis; however, it is currently not recommended. In a small number of cases, the test itself can cause laminitis and *any* risk of laminitis is too great of a risk. It has also been determined that it is no more accurate for the diagnosis of PPID than the endogenous ACTH test. In an article Correlation of Pituitary Histomorphology with Adrenocorticotrophic Hormone Response to Domperidone Administration in the Diagnosis of Equine Pituitary Pars Intermedia Dysfunction published in Vol. 45 of the Veterinary Pathology in 2008, a team led by M.A. Miller tested the use of domperidone as an alternative test to diagnose PPID. Their results indicate that the domperidone test could be used as an alternative to other tests available 1. While the results of this experiment are interesting, the really fascinating piece of the article was barely mentioned. They performed this experiment by taking information about the horse, then testing for ACTH after administration of the domperidone. They euthanized the horses, dissected out the pituitary gland, and sectioned it to be able to view the cells histologically. They were able to determine various sizes of the pituitary adenoma from a very small hyperplasia to a full blown adenoma. They graded the pituitary changes on a scale of 1-5 with 1 being very small and 5 being large. They then entered all of this information into a table.

3 Page 3 The information that they collected shows that the size of the pituitary adenoma was correlated to the amount of ACTH that it put out. The information from the table also showed that the size of the pituitary adenoma was correlated with the age of the horse. I have compiled information from their tables in the graphs. Considerations of Seasonal Rise: Besides the difficulty of the specificity and sensitivity of the tests available to diagnose PPID, there is the added component that ACTH rises in the fall. In young horses, it rises quickly, then returns to normal a few weeks later. In older horses, the rise is higher and lasts longer. At some point, the rise is either too high, or does not return to normal. In the northern hemisphere, the rise for younger horses begins in September, returning to normal in October. For older horses, the rise may begin as early as July and remain high until December. Treatment Options: There are currently a couple of treatments for PPID. This could be either pergolide or chastetree berry. Pergolide is the gold standard for treatment of PPID. It is safe and the most effective treatment available. Available by prescription only, it is also very affordable from compounding pharmacies in the U.S. Average prescriptions cost about $15-20 per month.

4 Page 4 Cyproheptidine used to be prescribed for PPID, but studies have shown that pergolide is a more effective choice. This is rarely prescribed for PPID currently. Chastetree berry is an herb that may be helpful with the external signs; however, its ability to affect the ACTH level is mixed and does not reliably reduce the ACTH every time. Studies have shown that about half horses have responded well to it, but the other half have not had any improvement at all. It has also been shown that the horses who do respond eventually need to go on pergolide, as it appears that the tumor continues to grow with the chastetree berry. For the amount needed to be administered, the cost is about the same as pergolide. Note: Personal communication. Dr. Kellon asked Dr. Eustace of the Laminitis Trust if the response of ACTH to CTB was different in mares versus geldings or stallions. After examining the data, he reported mares responded with a drop while males did not. This is still preliminary information and data needs to be corrected for time of year and be examined statistically. Regardless of sex, if using CTB you need to be monitoring ACTH. Treatment Consideration of PPID: During early PPID, treatment may only be necessary during the seasonal rise. The reduction in ACTH from the pergolide may help the older horses avoid fall laminitis. At some point, it will be necessary to treat these horses year-round to help maintain control of the PPID. During the fall rise, the pergolide amounts may need to be increased to still maintain normal ACTH. The goal is to never allow the ACTH to skyrocket. Some people have found that the pergolide amounts may need to double to maintain control. Risks of Undertreated or Untreated PPID: The long-term effects of untreated or undertreated PPID are devastating. The risks to horses are very real and increase as the pituitary gland enlarges and presses on adjacent structures. Laminitis is a very real risk, and with it, the pain of being unable to walk or move to any great extent. Some horses become blind due to the pressure of the pituitary gland on the optic nerve. Undertreated horses are also prone to infection due to an impaired immune system. The type of infection that is commonly seen in this scenario is of the nasal cavities. Loss of body condition, pain, and lethargy are also commonly seen. Take Home Message: Be Aware of PPID in Older Horses. PPID is a progressive disorder correlated to aging in the horse. Test for ACTH Levels. The test that is commonly used is the endogenous ACTH. Although any laboratory may be used, Cornell is the lab that I prefer.

5 Page 5 Trial Pergolide If Unexplained Lameness in The Fall. If your horse has suffered from fall laminitis and you cannot afford to test, you may ask your vet to trial pergolide to see if your horse has increased comfort in the fall with pergolide. Avoid Laminitis At All Costs. Laminitis is a devastating condition, which in many cases can be avoided. For more information, please go to or join the Equine Cushings and Insulin Resistance group at References: 1 Miller MA, Pardo ID, Jackson LP, Moore GE, Sojka JE. Correlation of Pituitary Histomorphometry With Adrenocorticotrophic Hormone Response To Domperidone Administration in The Diagnosis of Equine Pituitary Pars Intermedia Dysfunction - Vet Pathol. 2008;45(1): Credits: This article originally appeared in Dr. Eleanor Kellon's ezine, The Horse's Mouth. For subscription information, please go to

Cushing s Disease. Avondale Veterinary Group. Avondale House Strathaven Rural Centre Strathaven Lanarkshire ML10 6SY.

Cushing s Disease. Avondale Veterinary Group. Avondale House Strathaven Rural Centre Strathaven Lanarkshire ML10 6SY. Avondale Veterinary Group Avondale House Strathaven Rural Centre Strathaven Lanarkshire ML10 6SY Tel: 01357 520251 Cushing s Disease Equine Cushing s Disease (ECD), also known as Pars Pituitary Intermedia