New Knowledge on Diagnosing Equine Endocrine Disease
Learn how veterinarians are using recent research in their day-to-day practice to diagnose PPID, EMS, and ID
In theory, distinguishing between common endocrine issues in horses is straightforward: The shaggy one has Cushing’s, the fat one has metabolic syndrome, and the laminitic one can’t regulate insulin, right?
But researchers have learned there’s much more to diagnosing these conditions than what’s on the surface. And, perhaps more importantly, they’ve learned how an accurate diagnosis and subsequent treatment can prevent or reduce the risk of some of the life-threatening complications associated with endocrine issues.
We caught up with Amanda Adams, PhD, an associate professor and MARS Equestrian Fellow at the University of Kentucky’s Gluck Equine Research Center, in Lexington, and Gabrielle Faragasso, VMD, an intern veterinarian at Genesee Valley Equine Clinic, in Scottsville, New York. They offered insight on how veterinarians can best use recent research in their day-to-day practice.
While they’re not the only equine endocrine diseases, pituitary pars intermedia dysfunction (PPID, formerly referred to as equine Cushing’s disease), insulin dysregulation (ID), and equine metabolic syndrome (EMS) are the most common. They’ll be our focus in this article.
Endocrine diseases are complex. But that’s not the only reason diagnosing them has proven challenging.
First, says Adams, many practitioners must send samples to outside laboratories to analyze the substance levels of interest (such as adrenocorticotropic hormone, or ACTH, in PPID cases and insulin in ID and/or EMS cases).
“Most vet clinic labs do not have access to equipment needed to perform these assays,” she says. “Additionally, while the vet can just pull a quick blood sample and measure basal or resting levels of ACTH or insulin levels, oftentimes it’s best to perform dynamic testing. But these dynamic tests can be a bit more time-consuming, laborious, and expensive.”
And, importantly, Adams says, “there’s probably confusion as to what test to use and when and how. As we learn more, and as research keeps pushing the envelope, we change the guidelines and recommendations for diagnostic testing. This can be frustrating for folks and ultimately poses challenges.”
As is the case with many horse health issues, practitioners must balance research findings and clinical experience. Faragasso says her clinic holds regular “scientific journal” meetings, during which they discuss recent peer-reviewed studies and their applications.
Veterinarians need to “proceed with caution when considering new approaches that don’t yet have peer-reviewed validation behind them,” says Adams.
Pituitary Pars Intermedia Dysfunction (PPID)
Horses with PPID have an enlargement in the pars intermedia, a structure within the pituitary gland that plays a key role in hormone regulation. This, Adams says, results in increased output of various hormones (including ACTH), potentially leading to metabolic issues. It’s most common in older equids, which can make some early signs of disease (e.g., delayed shedding, lethargy, and muscle tone loss) easy to overlook because they’re also associated with aging. Signs of more advanced disease—a long hair coat, a potbellied appearance, decreased performance, abnormal sweating patterns, and excessive water intake and urination—are typically easier to identify as being associated with disease rather than aging.
Our sources agree that clinical signs still play an important role in identifying possible PPID cases. But the recommended testing methods have changed in recent years.
In the past, veterinarians often turned to an overnight dexamethasone suppression test; they’d collect a blood sample, give a dexamethasone injection, and then return the next morning to collect another blood sample to compare cortisol levels. Persistently high cortisol levels in the blood were suggestive of PPID. While veterinarians still use this test in some cases—“it does a great job with diagnosing late-stage PPID,” Adams says—it’s no longer the go-to assay.
Researchers currently recommend baseline plasma ACTH level tests and/or the TRH (thyrotropin-releasing hormone) stimulation test to diagnose PPID, Adams says. The former test simply measures ACTH levels in the bloodstream on a single sample. The latter is a dynamic test that gauges ACTH response to a stimulus (a TRH injection), making it more sensitive.
“If the horse has few or mild signs and is on the younger end of the age spectrum, it’s best to use the TRH stimulation test,” Adams adds. “But if the horse has many signs, a basal ACTH test can yield all the information you need to make a diagnosis.”
Other recent research and recommendations on the topic indicate:
- Retesting is advisable, with the same and/or other test, if results are inconclusive or do not match the obvious clinical signs.
- Evaluating treatment efficacy is likely best accomplished by assessing both clinical signs and baseline ACTH measurements, rather than a TRH stimulation test.
- The TRH stimulation test can be conducted following hay or forage consumption (so there’s no need to fast overnight), but it shouldn’t be used within 12 hours of a grain meal, which could alter ACTH concentrations.
- Stress and pain can alter ACTH concentrations, so avoid collecting samples in the 30 minutes after any type of potential stress (including trailering), during or immediately after an acute laminitis episode, anytime the horse is in pain, or within 24 to 48 hours of sedation.
- Researchers have long known that ACTH levels are highest in autumn, so they’ve historically recommended testing during other seasons. However, they’ve recently learned the variation is so high during the fall that it might be the best time to conduct baseline ACTH level testing. Adams cautioned that researchers still haven’t completely defined seasonal reference ranges for the TRH stimulation test.
- Ambient temperature can impact ACTH concentrations in blood samples by 5 to 12%, so samples should be refrigerated after collection and shipped cold. They should not be frozen, however, as multiple freeze-thaw cycles can also impact sample ACTH levels.
- Not all labs and assays are the same, so use the same facility for tests if you’re planning to compare the results. “Make sure you’re working with a reputable lab that has established reference ranges for each of the tests,” Adams says.
Finally, researchers know PPID and other endocrine disorders can develop in the same horse at the same time. She encourages practitioners to check each horse’s insulin status when they conduct PPID testing, because ID can significantly increase laminitis risk and requires careful treatment and management.
The horse’s pancreas produces the hormone insulin, which stimulates glucose uptake into metabolically active tissue, such as muscle, to use or store as energy. When cells in the metabolically active tissue don’t respond to the insulin, however, the body’s signaling system essentially instructs the pancreas to produce more insulin to try to elicit a response. These abnormally high blood insulin levels result in ID, which puts the horse at increased risk for potentially serious issues such as obesity, regional adiposity, and laminitis.
Adams says veterinarians traditionally use clinical signs and/or an oral sugar test (OST, which measures a horse’s insulin response following a high-carbohydrate stimulus such as corn syrup) to diagnose ID; however, because the condition doesn’t manifest the same way in all horses (i.e., ID horses don’t always become obese or develop laminitis), it’s easy to miss cases when relying on clinical signs alone. And, she adds, because ID appears to be a “driving factor and strongest predictor” of hyperinsulinemia-associated laminitis (formerly known as endocrinopathic laminitis), an accurate diagnosis is key to keeping affected horses laminitis-free.
Measuring baseline insulin levels can suggest ID in severely affected horses; for horses in the early stages of disease, the OST remains the gold standard dynamic test for diagnosis. But researchers have suggested considering several important factors before running the test:
- It might matter whether horses are fasted (for a minimum of three to six hours, but often overnight) or allowed access to forage (but typically not grain) prior to testing. In a 2022 study Macon et al. showed that ID horses had significantly lower resting insulin concentrations when tested after a three-hour fast than their unfasted counterparts; however, they also found no difference between fed and fasted insulin responses to the OST in horses with and without ID. This suggests either fasted or fed tests can produce accurate results, provided veterinarians use the same type of test—fed or fasted—to evaluate the horse over time.
- If a vet opts for a fed OST, he or she should consider the type of forage the horse has consumed, as forages with low nonstructural carbohydrate (NSC) levels can produce much different insulin responses than those higher in NSCs.
- Researchers used Karo light corn syrup in developing the OST, but it’s not available in all countries or locations. Fortunately, corn syrup brand doesn’t appear to significantly impact insulin responses (Banse and Moser, 2019).
- Corn syrup dose can yield different information in specific cases. In one study, researchers (Jocelyn et al., 2018) showed a high dose (0.45 mL/kg) of corn syrup allowed them to better distinguish between ponies that had previously had laminitis (via higher serum insulin concentrations) and those that hadn’t, while a low dose (0.15 mL/kg) didn’t reveal the same differences. However, in another study, researchers (Macon et al., 2022) found no difference in insulin responses at 60 minutes post-corn-syrup administration at high or low doses in ID or non-ID horses. Ultimately, Adams, who was a co-author on the latter study, says, “these results indicate that a low-dose OST appears appropriate for diagnosing ID in horses, while a high dose could help with equivocal cases.”
- While it’s well-established that season impacts horses’ ACTH levels, researchers have recently learned it also appears to impact insulin responses—specifically in horses with ID (Macon et al., 2022). Horses with ID had more pronounced insulin responses following an OST in the spring than in the summer, along with higher base levels and insulin responses in the spring and winter than in the fall and summer. Horses without ID did not have such seasonal variations. Consider season when conducting OSTs, Adams says.
- Finally, conducting a TRH stimulation test prior to an OST doesn’t appear to have a negative impact, meaning veterinarians can screen for PPID and ID concurrently (Hodge et al., 2019).
Equine Metabolic Syndrome
Horses with EMS have a combination of conditions: They have ID (“This is the main, defining characteristic of EMS,” Adams says) and are generally obese or have regional adiposity. A cresty neck and abnormal fat deposits in specific areas—behind the wither and/or shoulder, over the ribs, and along the back and tailhead—are common. Some breeds, including certain ponies, Spanish breeds, gaited breeds, Morgans, Miniature Horses, Warmbloods, and donkeys, have an increased genetic risk of developing EMS.
Vets have long used clinical signs to identify EMS, and they remain an important part of the diagnostic process. But, Adams says, “clinical signs alone don’t always tell you if the horse has ID—not all obese horses have ID, and not all ID horses are obese—and it’s not obesity, per se, that sets a horse up for laminitis. It’s ID.”
Therefore, researchers recommend following ID diagnostic protocols, as well as carefully evaluating clinical signs and potential genetic risk factors, in horses suspected of having EMS.
Researchers are continually learning how to best diagnose endocrine disorders. As vets work these findings into their day-to-day practice, the horses are the ones seeing the biggest benefits. After all, a simple diagnostic test and subsequent treatment can result in material change.
“The results clients see are the most positive thing,” Faragasso says. “When we get a diagnosis and start treatment, I’ve had owners say, ‘I have my old horse back. I didn’t even realize how much had changed.’ It’s nice to see those results.”
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