Cover Story | Endocrinology

What Works and What Doesn’t for PPID and EMS/ID

By Paul Basilio

Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome and insulin dysregulation (EMS/ID) are clinically distinct but overlapping disruptions of the endocrine system.

Both conditions are quite common. Up to 20% of equids older than 15 years of age, and up to 30% of equids older than 30, are known to have PPID, while EMS/ID can occur in up to 50% of horses of predisposed breeds.

If diagnosed early enough, many horses with either or both conditions will respond well to dietary management and exercise; lifelong medical management will be necessary in all horses with PPID, and in some severe cases of EMS/ID. Both conditions can lead to hyperinsulinemia-associated laminitis (HAL), however, which is a potentially career- or life-ending condition. PPID can complicate HAL in horses with insulin dysregulation, so management of both conditions in horses that have them is best for an optimal outcome.

To help practitioners stay ahead of these conditions, Kelsey Hart, DVM, PhD, DACVIM (Large Animal), gave a run-down of the available treatments for each in a seminar sponsored by Boehringer Ingelheim.

PPID Treatments
In humans, treatment of a pituitary tumor would involve radiation or surgery using a transsphenoidal sinus approach. Mechanically and logistically speaking, that’s not a plausible option in horses with PPID.

“So, we leave the horse’s overactive pituitary gland in place and try to get it to chill out,” Dr. Hart said.

The approach to PPID management in horses is based on managing the decrease in dopamine, which—in non-PPID horses—inhibits the pars intermedia. In horses with PPID, however, neurodegeneration causes the dopamine-producing neurons to die, resulting in a decrease in dopamine and inhibition of the pars intermedia. The goal, therefore, is to replace the missing dopamine with a dopamine agonist—typically pergolide mesylate.

“We’re not curing the disease—this is life-long therapy,” Dr. Hart said. “Pergolide doesn’t stop the loss of the horse’s dopamine-producing neurons, so they will typically require some type of dose increase as they age.”

The most common adverse effect of pergolide is inappetence, but it typically resolves after lowering or dividing the doses, or after pausing administration, getting on full feed, and resuming with a reduced dose—working back up to the full dose.

Cyproheptadine—a serotonin antagonist—is typically not effective against PPID on its own, but it may be beneficial in some refractory cases when given with pergolide.

Another dopaminergic agonist, cabergoline, has been generating some buzz recently. There are limited safety and efficacy data, but an uncontrolled, unblinded, retrospective study from the United Kingdom found that horses showed clinical improvement and improvement of their adrenocorticotropic hormone levels, according to a study Dr. Hart participated in.
“There was a pretty high reported incidence of inappetence in that study,” Dr. Hart said.

EMS/ID Treatments
In contrast to PPID, there are several treatment goals in horses with EMS/ID:

• Help the horse reduce their adipose tissue stores if they are obese
• Manage their insulin dysregulation
• Prevent or manage laminitis

“For the first 2 goals, diet is critical,” she explained, adding that a diet that includes low non-structural carbohydrates (NSC) is a key component of management.

In general, the goal is to include a diet that has less than 10% NSC. Hay can undergo testing to determine its NSC content, but Dr. Hart said that would require testing every batch, cutting and truckload of hay, which can be a challenge for owners.

“Most of the time we’re going to soak grass hay, ideally for 60 minutes in cold water,” she said. “This helps the hay lose sugar, but it also helps it lose protein, vitamins, and some energy.”

The goal is to offer about 1.5% of the horse’s body weight in soaked hay, which corresponds to about 1.75% to 2% by dry weight. Dr. Hart also recommended adding a ration balancer or a low-NSC senior or complete feed in addition to the soaked hay to provide adequate protein and vitamins lost during soaking.

Alfalfa hay is another good option for leaner horses with insulin dysregulation, as it is typically low in NSC and high in calories.

If the horse must graze, try to let them graze in the morning. NSC levels are usually at their lowest in the morning, and they will likely increase during the day and in periods where the grass is stressed due to heat or frost.

Exercise is another critical component of care for these horses. Even if an obese horse’s weight does not change, exercise alone can improve their insulin sensitivity and insulin responses.

“The trouble is that we often diagnose them when they’re already laminitic, so they may not be mechanically stable enough to exercise,” Dr. Hart said.

As a compromise, she starts laminitic, insulin-dysregulated horses in a stall with deep bedding during the acute phase. After the horse is stable in the stall, can walk comfortably and is stable on radiography, she places them in a small paddock with soft footing. In some cases, she’ll work with a veterinary podiatrist or the horse’s farrier to place clogs on the horse for frog support. The horse then has its turnout space and time increased gradually.

“I might add groundwork or riding at a walk in horses with laminitis, but that can take many months,” she added. “It generally takes about a year to grow a hoof, and they’re usually 3 to 6 months or more into recovery before they can do any sort of forced exercises.”

Medical therapy may not be needed in all insulin-dysregulated horses. If the horse’s feet are okay and they can be managed with diet and exercise, then that might be enough. However, there are options for horses that don’t respond to diet and/or exercise, or in those with laminitis—with one caveat.

“You need to know whether they have PPID,” Dr. Hart said. “If they do, you have to manage that first, because you will not get the insulin dysregulation under control if you don’t.”

Drugs such as metformin and pioglitazone have been used with some success, but studies show variable efficacy data, and metformin is poorly bioavailable in horses. Levothyroxine powder (0.1 mg/kg/day PO) can be helpful in aiding weight loss, but it is not a long-term treatment, as the thyroid function is normal in these horses. Once a horse achieves an ideal weight, the drug should be tapered off slowly.

Sodium glucose cotransporter 2 (SGLT2) inhibitors appear to be effective and are generally well tolerated, but the drugs may be expensive, and complications are possible. The drugs inhibit glucose reabsorption in the kidneys, allowing much of the glucose to be eliminated in the urine. The drugs are quite effective at decreasing postprandial insulin concentrations in many horses, but they will cause an increase in triglyceride levels. In some cases, the horse’s serum may appear turbid/white.

“This is usually transient and not problematic unless the horse stops eating or has some underlying liver disease,” Dr. Hart said.
A typical regimen for SGLT-2 inhibitors in horses with severe ID/hyperinsulinemia-associated laminitis consists of a 3-month course, followed by a taper and monitoring.

“Some horses do seem to need to stay on them long-term, but that is not the goal of therapy, and is often not affordable or desirable,” she explained. MeV

Dr. Hart has received consultancy fees and research support from Boehringer Ingelheim, Kentucky Performance Products and Zomedica Inc.

For more information:
Sundra T, Kelty E, Rossi G, et al. Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction. Front Vet Sci. 2024;11:1332337. doi: 10.3389/fvets.2024.1332337
https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2024.1332337/full