Diagnosing and managing horses with equine metabolic syndrome (EMS), pituitary pars intermedia dysfunction (PPID), or a combination of the two can be tricky! This explains why the Table Talk session focusing on these conditions was so popular during the 2022 American Association of Equine Practitioners convention held Nov. 18-22 in San Antonio, Texas. This standing room-only session was moderated by Dianne McFarlane, DVM, PhD, MS, Dipl. ACVIM, Chair of the Department of Large Animal Clinical Sciences at the University of Florida, and Harold Schott, DVM, PhD, Dipl. ACVIM, Professor of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University.
PPID
Beginning with PPID, McFarlane and Schott relayed that many negative horses can fall into the equivocal range when using the 2021 EEG guidelines for basal ACTH concentration. The equivocal range should be used to identify horses to either follow over time for development of clinical disease or to perform additional diagnostics. Horses in the equivocal range have not been diagnosed with PPID but can’t be ruled out, either.
“This means that if a horse has an ACTH level of 25 pg/mL and only mild clinical signs of PPID, a TRH could be considered to provide further support of a diagnosis of PPID,” Schott explained.
Some of the attendees indicated they performed TRH stimulations as a first-line test rather than only basal ACTH values. The rationale was that if the ACTH results are equivocal then the practitioner would need to go back to the farm anyway, so it’s best to start with the TRH stimulation test to begin with.
Fine-Tuning the Testing: Season Matters
When testing horses, practitioners need to consider the season.
“A low ACTH in the fall remains strong evidence that a horse doesn’t have PPID. A high ACTH in the fall, however, is hard to interpret due to the magnitude of the seasonal increase being so variable among different horses without PPID. Similarly, we currently do not recommend a TRH stimulation in fall, because there is a wide range of ACTH responses to TRH in the fall in apparently normal horses. And, as yet, we do not have a robust database to differentiate between normal and PPID horses,” McFarlane shared.
By “fall” the moderators were referring to August 1st to October 31st in the northern hemisphere.
As pointed out by one practitioner, sometimes an owner will insist you do the test regardless of season.
McFarlane responded by saying, “Yes, testing can be done year-round. However, you may only be able to use the test to rule out PPID in the fall.”
Follow-Up
One way to monitor PPID horses, attendees suggested, is relying on clinical signs.
“If you’re happy with the clinical response, follow-up testing may not be warranted,” one practitioner remarked.
McFarlane added, “Clinical improvement and client satisfaction is definitely a legitimate measure of treatment success.”
But some owners want to have actual “numbers,” in which case testing can easily be performed.
“If the horse had a ‘normal’ baseline ACTH and was diagnosed by TRH stimulation then TRH stimulation will be the test of choice for follow-up,” recommended McFarlane.
Client Education
Overtreating
One problem identified by practitioners is that some owners read too much! Some horses might not need to be treated, especially if their results were equivocal to begin with.
“The equivocal zone is now so big now that it is becoming more common to put a horse on drugs that may not need it. The TRH is just a test suggesting that these horses need to be followed,” one attendee interjected.
One way to prove to an owner that a horse doesn’t need treatment is to wean off the pergolide
in the spring and reassess (recall that the TRH is not recommended in the fall).
“This is a life-long, slowly progressive disease. Consequently, we don’t need to jump to life-long therapy right away for a horse early in the course of disease,” advised Schott.
Undertreating
Even when the mutual decision is made to treat a PPID horse with pergolide, practitioners expressed their frustration at poor owner compliance. Horse acceptance of the medication was also mentioned as a problem, with one practitioner saying, “You can’t use the oral product if you can’t get the horse to eat it. Even with apples, bananas or grain.”
One attendee mentioned using a compounded injectable formulation of cabergoline that lasts two weeks, but McFarlane indicated she has not used that product personally. Because it is compounded and therefore not approved by the Food and Drug Administration, it is necessary to follow the FDA regulations for extra-label drug use.
The cost, as one would expect, is a little more than Prascend.
Endocrine Confusion
McFarlane relayed that they were seeing more and more young horses being treated for PPID, which is concerning her.
“There is still confusion between which horses have EMS, which have PPID, and those with both diseases concurrently. In horses that are young with only obesity and laminitis as clinical signs, they are more likely to have just EMS, even if the ACTH is in the equivocal range. In addition, the ACTH can be quite high in the fall in horses with EMS and certain breeds like ponies despite them not having PPID. Finally, illness and stress can also cause rises in ACTH.”
Starting Pergolide, Instituting Management
When initiating treatment, practitioners wanted to know what dose to start at. A quarter or half of a 1 mg tablet so there is no appetite loss? How high of a dose can one prescribe? Can Prascend be combined with any other medication to help control PPID?
“It’s reasonable to start with 0.5 mg/day of pergolide and see if there is a response based on clinical signs. If improvement in clinical signs is not recognized after one month, try bumping up the dose to 1 mg/day. I don’t tend to go above 3 mg,” recommended Schott. “Remember when adjusting the dose that the cost of the medication will also increase, and it’s already an expensive drug.”
McFarlane added, “The cap of 3 mg is arbitrary (i.e., not based on clinical or evidence-based data) and Prascend is usually cost-prohibitive after this dose. Plus, the chances of getting more effect at 5 mg is small. It could be that there is a point in the disease when horses become unresponsive to pergolide. There might be too much damage to the pituitary gland for pergolide to do anything.”
Some veterinarians elect to add cyproheptadine (0.5 mg/kg once a day) in horses not responding to the higher doses of pergolide.
It should be noted that pergolide doesn’t extend life expectancy, but it does improve quality of life, as the moderators pointed out.
EMS
Making the move to turn the discussion towards EMS, McFarlane advised testing all PPID horses for EMS.
“It is critical to get a handle on and control both diseases. In horses with both diseases, insulin concentrations are higher than in horses with either EMS or PPID alone, and horses with both PPID and EMS typically have worse laminitis.
Testing for Insulin Dysregulation (ID)
The oral sugar test (OST) was an extremely popular first-line test for attendees, and some routinely measured basal insulin levels before performing the OST.
For clients who are located a distance from the veterinary practice, adjustments can be made to allow an OST to be performed on the farm.
“When performing an OST a basal insulin level may not be necessary to measure as we are most interested in the dynamic insulin response 60-90 minutes after dosing with karo syrup,” advised McFarlane. “In this case, have the owner give 0.15 mL/kg light Karo syrup 60-90 minutes before you plan on arriving,” she added.
The moderators agreed that basal insulin can be a good screening test when it’s abnormal. When it’s normal, however, you can get a false negative.
The higher sugar dose (0.45 mL/kg) wasn’t better at diagnosing ID than the 0.15 mL/kg dose according to a recent study in horses by Macon, et al. (2021). Plus, the volume at the 0.45 mL/kg dose is huge, especially for a warmblood! It might be more useful in some breeds, such as ponies. Be sure to adhere to the guidelines for the different cut-offs for the different dosing regimens.
For the insulin tolerance test, a single dose of insulin should cause a 50% decrease in glucose, which can be measured with a hand-held glucometer. A <50% decrease in glucose is consistent with an abnormal (decreased) insulin sensitivity.
McFarlane said, “This might be a good alternative for a horse that doesn’t test positive on the OST, but you still suspect ID. But don’t do it in a skinny horse as you can create hypoglycemia if the horse is insulin sensitive! If any horse begins showing muscle fasciculations, you’ll need to give glucose. Make sure to have some 50% dextrose on hand.”
There are “healthy obese” horses that don’t have EMS, and there are skinny horses that still have EMS. In the EMS horse that is thin, rule out PPID—a catabolic disease that causes muscle loss, advised McFarlane.
One attendee asked if leptin was useful in our assessment of these horses.
Leptin is released from adipose tissue and tends to correlate to how fat the horse is. Using body condition scoring, veterinarians and some owners (when taught) can get a good assessment of obesity by looking at the horse (although as one attendee pointed out, you can’t assess intra-abdominal adipose tissue).
“It can still be a useful test because people like numbers! Sometimes you can use it to prove to an owner that their horse is overweight and use the leptin values as a measure of weight-loss success…a similar practice as assigning a cresty neck score,” McFarlane advised.
Sneak Peek at SGLT2i’s
Management (nutrition and exercise) and metformin were only briefly discussed before jumping in a new direction: sodium glucose cotransporter 2 inhibitors, or SGLT2i. These medications, specifically ertugliflozin, were also discussed in a separate session during the Convention by Tania Sundra, BSc, BVMS, MANCVS (Equine Medicine) from Avon Ridge Equine Veterinary Services in Brigadoon, Western Australia (see page 239 of the conference proceedings or watch the on-demand video).
SGLT2i’s are a class of medication that blocks the resorption of glucose from the kidneys, thereby reducing circulating levels of glucose and insulin in the bloodstream.
In Sundra’s study, 51 horses diagnosed with EMS and hyperinsulinemia-associated laminitis (HAL) were treated with 0.05 mg/kg ertugliflozin PO q 24 hr for 30 days. Key findings were:
- A significant improvement in basal insulin levels was noted (>300 microu/mL to 43 microu/mL) at 30 days; and
- Decreased modified Obel laminitis score from 10/12 to 1/12 at 30 days (P<0.001).
From a safety/adverse effect standpoint, Sundra noted that some horses developed polyuria and polydipsia in response to treatment, and that mild to moderate hyperlipidemia occurred in the majority of horses at 30 days, but triglyceride levels decreased by 60 days. Clinical signs of hyperlipemia were not observed.
“From what we have seen so far, ertugliflozin also appears to work well to improve the comfort (decreasing laminitis pain) of EMS horses with HAL. However, we still need long-term data for SGLT2i’s, larger case numbers, and more robust studies to be confident of their benefits. We also need pharmacokinetic studies,” added David Rendle, BVSc, MVM, CertEM (IntMed), Dipl. ECEIM, a specialist based in the United Kingdom involved in the study.
In Australia, where the study was conducted, ertugliflozin is a reasonably priced human anti-diabetic medication and is available as an extemporaneous preparation for horses. In the United States, it is also available as a human medication (tradename is Steglatro) but is more expensive.
Some attendees indicated they are already using it (and have seen positive outcomes).
“Although more work is needed to ensure the safety and efficacy of this class of drugs, this is the most exciting development that we’ve seen in a long time for EMS,” enthused McFarlane to end what arguably can be described as one of the most popular sessions at this year’s Convention.
For more information regarding current recommendations, refer to the Equine Endocrine Group (EEG) guidelines for pituitary pars intermedia dysfunction (PPID) published in 2021 and equine metabolic syndrome (EMS) published in 2022.
