Pituitary pars intermedia dysfunction (PPID) is a complex and common endocrine disease, particularly among older horses. Many of the guidelines for management and decision-making, however, lack objective evidence. So David Rendle, BVSc, MVM, CertEM (Int Med), Dipl. ECEIM, FRCVS, an independent consultant and European veterinary specialist in equine internal medicine based in the U.K., reviewed existing literature to formulate a “best practice” for monitoring affected horses. He presented his recommendations at the 2021 British Equine Veterinary Association Congress, held Sept. 4-7 virtually and in Birmingham.

Reviewing What We Know

First, Rendle shared recent study findings that illustrate the challenges of managing PPID horses and what we’re learning about the disease.

According to Tatum et al., 76% of horses treated with pergolide (the mainstay medication for PPID) will have some subjective improvement in clinical signs. However, “when we look at ACTH (adrenocorticotropic hormone, which the pars intermedia secretes more of in affected horses) responses to pergolide, there’s a poor correlation with changes in clinical signs, which is frustrating,” Rendle said. “That brings up a couple of important questions: Does this undermine the value of our clinical assessments, because they’re very subjective? Does this undermine the reliability of ACTH as a marker?”

Other studies have shown 20-74% of treated horses show improvements in ACTH concentrations, with “relatively low returns to normal ACTH concentrations,” he said.

Then there’s the complicating factor that horses’ ACTH levels fluctuate naturally with the seasons, often rising in autumn and returning to normal in spring.

In a recent study by Knowles et al., 66% of horses with high ACTH responses in fall improved spontaneously by spring without treatment. “We’ve always thought testing in the autumn was more accurate, but some recent studies suggest testing is more accurate in spring,” said Rendle. “If this is the case then you run the risk of getting false positives in autumn. The jury is still very much out on when is the best time to test.”

Perhaps more important than ACTH levels, however, are insulin concentrations. “If we’re looking to control laminitis (a painful hoof disease PPID horses are at risk of developing) in these PPID cases, it’s their insulin responses we really need to be worrying about,” he said.

Recent data from McGowan et al. demonstrated that insulin concentrations in PPID horses on pergolide don’t improve well consistently, and there is no evidence that pergolide treatment reduces the risk of laminitis.

Lastly, owner compliance when it comes to treating PPID horses is often lacking. One recent study showed only 48% of owners purchased their veterinarians’ recommended doses of pergolide. So, “rather than assuming pergolide is not working, what we really need to do first is scrutinize is compliance,” Rendle said.

A Logical Approach to Monitoring Affected Horses

While there’s no one-size-fits-all best practice for monitoring horses with high ACTH levels suspected of having PPID, Rendle devised an algorithm he hopes can guide veterinarians’ and owners’ decision-making:

Rendle emphasized the importance of focusing more on a horse’s clinical signs than lab results, “particularly if they’re discordant.” If veterinarians are doing lab tests, they should follow up the initial diagnosis and implementation of pergolide administration with another test two to four weeks later to determine the drug’s effect on ACTH levels and adjust management as needed.

If ACTH concentrations don’t lower with treatment, “please think about compliance; don’t just assume the drug’s not working,” Rendle said. And if they do lower, “don’t just rest on your laurels,” he said. “Consider the possibility you have a false positive. Consider the horse has gone back to normal because of seasonal changes or biological variation, not treatment. I will often reduce the dose and try to titrate off treatment just to establish whether they are false positives. Clearly if they have overt clinical signs, that’s not necessary, but there are lots of horses where the diagnosis is tricky.”

Once you’ve got the ACTH levels where you want them, retest biannually to monitor them, Rendle said. Don’t overlook the importance of insulin as a marker of laminitis risk, he added. “Given the choice of insulin or ACTH, I would always rather know the insulin concentration.”