Current EMS and PPID Testing Recommendations

The earlier you can detect endocrine conditions such as pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS), the better chance you have of preventing associated laminitis in affected horses. Fortunately, veterinarians understand how to diagnose these conditions better than ever and are progressively fine-tuning their methods.

At the 2017 American Association of Equine Practitioners Convention, held Nov. 17-21 in San Antonio, Texas, Teresa Burns, DVM, PhD, Dipl. ACVIM, an associate clinical professor of equine internal medicine at the Ohio State University College of Veterinary Medicine, in Columbus, reviewed current recommendations for EMS and PPID diagnostic testing.

Why Testing Is Important

“Endocrinopathic laminitis is reported to be the most common form encountered in equine veterinary practice,” said Burns, and PPID and/or EMS frequently accompany it. “Practitioners should be aware of diagnostic testing methods for these conditions that are available and clinically useful, as well as how to use them to most strategically manage their patients effectively. There’s continuous refinement in which tests are used and which are most appropriate for each patient.”

EMS Testing

“EMS is among the most common endocrine disorders of adult horses and is currently defined as overweight/obese body condition, clinicopathologic evidence of insulin dysregulation (excessive insulin response to oral sugars, evident as postprandial hyperinsulinemia, fasting hyperinsulinemia, or insulin resistance based on when it occurs), and laminitis (historical or current),” Burns said.

The goal of diagnostic testing is to assess and identify abnormal insulin and glucose dynamics, she said.

Veterinarians can garner a substantial amount of information about a horse’s EMS risk simply by evaluating his signalment (age, breed, sex, etc.), history, body condition, laminitis status, and other clinical signs. Regional adiposity (localized fat deposits) and a cresty neck, for example, are associated with EMS. Burns cautioned that not all EMS/ID horses are overweight, so she encouraged practitioners to perform testing to confirm EMS status.

She also noted veterinarians should interpret test results carefully. Certain medications (such as corticosteroids or levothyroxine) can impact test results, as can additional diseases or conditions affecting the animal (mainly problems that cause significant inflammation and/or physiologic stress, such as pneumonia, colitis, recent major surgery, or significant hemorrhage, at least temporarily, she said). Additionally, very high pain levels can influence results. More research is needed for definitive recommendations, but Burns said it might be beneficial to delay testing until a horse is no longer acutely painful.

She added that the common recommendation for horses undergoing testing is to provide low-nonstructural-carbohydrate (NSC) hay the night before, then have the horse fast for about two hours before the veterinarian runs the test.

Current diagnostic testing options include:

• The insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT), Burns said, is one of the gold-standard tests for assessing insulin sensitivity, but it takes several hours to collect samples. The veterinarian administers intravenous (IV) glucose to the horse, followed by insulin 20 minutes later. Then he or she measures blood glucose and insulin levels frequently, every minute to every 5 to 10 minutes for about three hours. The FSIGTT can be carried out in a field setting but, is time-consuming and expensive.
• The euglycemic-hyperinsulinemic clamp is considered the other gold-standard method of quantifying insulin sensitivity because it directly measures how much glucose leaves the blood in the presence of insulin. However, this technique is not easily performed in the field, limiting its usefulness in day-to-day veterinary practice.
• Assessing basal insulin and glucose concentrations is easy and cost-effective, Burns said, but is not dynamic (meaning they only capture one result from a moment in time, rather than multiple results over a span of time), has a low sensitivity (the probability that the test will be positive when the horse has EMS), and commonly produce false negatives. These measurements could be used as an initial screen, though, to be followed up with a dynamic test on at-risk horses, she said.
• The oral sugar test, a dynamic test, involves collecting a blood sample during the morning hours, followed by administering light Karo (corn) syrup orally and collecting another blood sample 60 to 90 minutes later. The veterinarian then evaluates both samples for insulin levels. Burns said this test is easy to perform in the field but tends to have low sensitivity.
• The combined glucose-insulin tolerance test (CGIT), another dynamic test, involves the veterinarian administering glucose and insulin intravenously, then measuring blood glucose and insulin levels over the next several hours. This is also easy to perform in the field.

While seasonality is important when conducting PPID testing, Burns said it remains unclear whether this is the case with EMS testing. She said in one study researchers showed that blood glucose levels were likely to be lower during the summer in Central Ohio horses, but other researchers have found no difference among the seasons.

PPID Testing

Burns said PPID (a disorder of the pituitary gland’s pars intermedia caused by an adenoma, or a type of tumor, is a common endocrinopathy of aged horses.

“Severe or chronic PPID is typically not a diagnostic challenge, given that the diagnosis can often be suggested by clinical signs alone,” she said, particularly in horses older than 18 to 20. Such signs include hypertrichosis (excessive hair growth and/or delayed haircoat shedding), muscle wasting, abnormal fat distribution, laminitis of unknown origin, recurrent infections, polyuria (excessive urination), and polydipsia (excessive thirst), among others.

“The clinical presentation of PPID in younger horses or those in the early stages of disease is more variable,” she added, “and diagnosis of these cases is more challenging and often relies heavily on the results of diagnostic testing.”

The current gold standard for PPID diagnosis is histopathology (looking at cell structure under a microscope) of the pars intermedia, Burns said. Unfortunately, this can only be carried out post-mortem, and even with this method scientists can disagree on what constitutes a case.

“One study showed that seven diplomates of the American College of Veterinary Pathology only had fair agreement about whether horses with PPID actually had PPID,” she said.

When it comes to diagnostic testing in the live horse, no method is 100% accurate. Burns cautioned that post-mortem exams only “agreed with” diagnostic testing 79% of the time. As such, she recommended practitioners use multiple diagnostic tests, including:

• Adrenocorticotropic hormone (ACTH) test: The pituitary gland normally produces ACTH in small amounts. In PPID horses, however, the gland overproduces ACTH, which is detectable as higher-than-normal ACTH concentrations in a blood sample. With this test, veterinarians only must draw one blood sample, but Burns cautioned that an ACTH increase is not necessarily specific for PPID in horses, and how recently the horse has eaten could impact the results. The ACTH test might be useful for pinpointing horses that should have a follow-up evaluation with a more specific test or be retested in three to six months.Additionally, Burns explained that ACTH levels vary naturally throughout the year, peaking in the fall. While veterinarians used to avoid testing in the fall for that reason, researchers now believe it could be the ideal season to test because PPID horses’ levels rise substantially more in the fall than those of healthy horses.
• Dexamethasone suppression test (DST): This test measures circulating cortisol levels 19 hours after administration of the steroid dexamethasone. The drug failing to suppress circulating cortisol levels suggests PPID. While veterinarians once considered this the gold-standard PPID test, more recent research indicates it’s not superior to measuring ACTH to diagnose PPID, even in its earlier stages. Further, dexamethasone administration might carry a small risk of exacerbating laminitis in some PPID-affected horses.
• Thyrotropin-releasing hormone (TRH) test: The TRH test stimulates the pars intermedia, resulting in a greater increase in plasma ACTH concentrations in PPID-affected horses than in normal horses. This test involves collecting two blood samples—before and 10 to 30 minutes after IV TRH administration—to measure ACTH concentrations. Burns said the TRH stimulation test is the most sensitive option available, but season can also impact results and researchers haven’t yet determined seasonal reference ranges for this test (like those available for assessing ACTH levels).
• α-Melanocyte Stimulating Hormone (α-MSH): This hormone is a product of the same pro-hormone as ACTH; the pituitary gland’s intermediate lobe—the area affected by PPID—almost exclusively produces it. This means the α-MSH could be a more specific test for intermediate lobe dysfunction than ACTH itself (which is also produced by other pituitary gland regions normally). Burns noted that it performs well in research settings, but a commercial test for use in day-to-day practice isn’t yet available.

The Bottom Line

“The primary goal of equine veterinarians when treating horses with PPID and EMS is to prevent the medical complications of these conditions, such as laminitis, which can be career- and life-limiting,” Burns said. “Early detection and prevention of these complications will likely hinge upon diagnostic testing of mildly affected horses, to identify and treat those with early disease. Fortunately, these testing methods are rapidly evolving toward both improved accuracy and ease of use in the field, which will hopefully enhance their utility for improving the health care and outcomes for equine populations.”