Normal Aging or PPID?

Don’t be fooled by the symptoms of this serious hormonal disorder, more commonly known as Cushing’s disease.

You’ve noticed that your elderly horse is staying shaggy a little longer every spring, losing some muscle along his topline and acting a little lazier than usual. It’s all just a normal part of equine aging, right? Maybe not. These are also symptoms of a disease known as pituitary pars intermedia dysfunction, or PPID. And, while it’s not typically fatal, it can radically reduce your horse’s quality of life without proper care.

One physical sign of a horse with PPID is long hair that is often wavy or curly. Another side effect is skin infections caused by a compromised immune system.

In this article, we get expert insights on PPID from James Carmalt, VetMB, PhD, DABVP, DAVDC, DACVSMR, DACVS, professor of large animal clinical sciences at the Western College of Veterinary Medicine in Saskatchewan, Canada, and Nicholas Frank, DVM, PhD, DACVIM, professor and associate dean for academic affairs at Tufts University Cummings School of Veterinary Medicine in North Grafton, Massachusetts. Both veterinarians have a particular interest in endocrine (hormonal) disease in horses, including PPID.

Plus, in a sidebar on at the bottom of this article, Nicole Baergen, a dressage groom and amateur rider based in Wellington, Florida, shares a first-person account of what it’s like living with and competing a PPID horse.

What is PPID?

PPID is considered the most common endocrine system disorder of older equids, including horses and ponies of every breed, as well as donkeys and mules. While it can occur in younger horses, it’s most often found in those age 15 and older and may affect anywhere from 10 to 30 percent of horses in that age group.

PPID was once more commonly known as Cushing’s syndrome, after neurosurgeon Harvey Cushing, who first identified the disorder in humans. (It can also affect canines.) As its name indicates, the disease involves the pars intermedia—a lobe of the pituitary gland. The pituitary gland, located at the base of the brain, is a key part of the endocrine system, producing hormones that help regulate important functions throughout the body. (See sidebar at the bottom of the article for a glossary of terms.)

In a normal, healthy horse, explain Dr. Carmalt and Dr. Frank, nerves deliver the chemical dopamine from the hypothalamus—often referred to as the brain’s control center—to the pituitary gland. There, the dopamine acts like a brake on the pars intermedia, regulating hormone production, says Dr. Carmalt.

In PPID cases, though, the nerves from the hypothalamus degenerate, and dopamine production decreases due to aging and oxidative damage (damage to cells and tissues that can lead to a number of diseases), says Dr. Frank. What we don’t know is why this process happens faster in some horses than others, he adds. Without its dopamine brake, the pars intermedia goes into overdrive.

To meet the perceived additional demand, the gland’s cells grow in size and number, creating small tumors called pituitary adenomas. These cause the pars intermedia to produce more hormones, including adrenocorticotropic hormone, which plays a role in controlling the horse’s stress response and is often used for diagnosing the disease (more on this below).

In a healthy horse, nerves deliver dopamine from the hypothalamus to the pituitary gland, where it regulates the pituitary gland’s hormone production. In PPID cases, the nerves from the hypothalamus degenerate and dopamine production decreases.

What are the signs of PPID?

There is a long list of symptoms that could indicate your horse has PPID, but not all horses will display all symptoms, says Dr. Carmalt—and many symptoms could be signs of other disorders. One of the red flags most indicative of PPID and noticeable early on, he says, is a coat that’s slow to shed.

“If all the other horses have shed out, and yours still has long guard hairs under his jowls, behind his elbows or on his belly, that’s a sign,” he says. “By the time the horse is super hairy, he’s probably had the condition at a low level for a number of years.”

Other early indicators, says Dr. Frank, are the horse not performing well or seeming more lethargic than usual. Or, he adds, “the horse may have been an easy keeper and now seems to be losing condition, and muscle mass across the topline may be decreasing.”

Additional physical signs of PPID include:

  • Long hair that’s often wavy or curly
  • Muscle atrophy over the hindquarters
  • Fatty deposits on the crest of the neck, tail head or shoulders
  • A potbelly
  • Excessive sweating or unusual lack of sweating
  • Increased drinking and urination

Other symptoms are invisible to the naked eye, but you may notice side effects of these factors over time. They include:

  • Frequent infections, particularly sinus and skin infections caused by a compromised immune system due to low white blood cell counts and elevated levels of the hormone cortisol
  • Frequent hoof abscesses
  • Laminitis, caused by the development of insulin dysregulation, where the horse has high concentrations of insulin in his blood
  • Reproductive abnormalities, such as infertility or abnormal heat cycles in mares
  • Dental disease
  • Increased intestinal parasite load
  • Lameness, particularly suspensory ligament damage
  • Other diseases, such as recurrent uveitis (a form of eye inflammation) and heaves

When in doubt about whether a symptom indicates PPID, Dr. Carmalt suggests it’s better to call your vet for an exam, because some effects of the disease can lead to long-term issues. For instance, if your horse is PPID-positive and that leads to a laminitic episode or suspensory ligament damage, he could face a lengthy layoff and permanently reduced performance ability.

Diagnosing the Disease

You may have noticed that many PPID symptoms look a lot like the signs of normal aging. To determine what you’re truly dealing with, your vet can examine your horse and run diagnostic tests. There are two tests most commonly used for diagnosing PPID.

  • Thyrotropin releasing hormone stimulation test is typically used when a horse shows few symptoms and is suspected to be in the early stages of the disease. At this point, explains Dr. Frank, a horse may be producing more hormones than usual, but the amount is spread throughout the entire day. So taking a single blood sample may not show any changes. But injecting TRH intravenously stimulates the release of ACTH, says Dr. Carmalt.
  • To conduct this test, your vet will take a baseline blood sample before injecting TRH and another blood sample 10 minutes later. If the pituitary gland is storing more ACTH than usual, the TRH will release it, and the second blood sample will show high levels of the hormone, indicating your horse has PPID. If the test results are negative, your vet may recommend repeating the test in six to 12 months.
  • Resting adrenocorticotropic hormone test is commonly the diagnostic choice when a horse has more obvious PPID symptoms. As the disease progresses, heightened ACTH levels may be more noticeable in a single blood sample—which is all that’s required for this test. If the level of ACTH in the sample is above normal, it means a positive PPID diagnosis. If the results aren’t definitive, your vet may suggest also running the TRH stimulation test.
  • Interestingly, normal ACTH levels change by season, naturally increasing from mid-July to mid-November, say Dr. Carmalt and Dr. Frank. So veterinarians can use a season-specific reference table to help evaluate the results of the ACTH test based on time of year.

If test results aren’t definitive or an owner doesn’t want to do the tests, your vet may suggest going straight to PPID treatment, says Dr. Carmalt. This tactic is typically only used if your vet has a strong reason to believe the horse has PPID. You’ll then monitor the horse’s condition over several months to see if symptoms improve (more on this below).

Given the many potential health complications that can be connected to PPID, your vet may suggest running additional tests to evaluate the horse’s overall health, including:

  • Checking for high blood insulin concentrations
  • Complete blood count
  • Serum biochemistry profile
  • Urinalysis
  • Foot radiographs (if laminitis is suspected)

The Gold Standard PPID Treatment

Unfortunately, there is no cure for PPID, and an affected horse will require ongoing treatment and care. However, the right management plan can greatly improve the horse’s quality of life and even allow him to continue his performance career.

The medical treatment of choice for years has been pergolide mesylate, which is sold in the U.S. under the brand name Prascend®. It is the only FDA-approved equine PPID drug in the country. Dr. Carmalt explains that it acts like dopamine, essentially fooling the horse’s pituitary gland into putting on the brakes and decreasing hormone production.

Prascend has a low risk of side effects with the most common being a loss of appetite and an increase in energy or excitability. To lower the chance of these issues, the general recommendation is to start treatment with a low dose of the drug, such as a quarter pill, allowing the horse’s system to gradually adapt. The dosage may need to be adjusted over time depending on how the horse responds with the goal of gaining the most benefit with the fewest adverse effects.

Once you start treatment, you may begin to see improvements as soon as a week to 10 days, says Dr. Carmalt, with other symptoms typically resolving in three weeks to a month. If your horse doesn’t improve, your vet may adjust the Prascend dosage or add other treatments, says Dr. Frank.

It’s worth noting that Prascend isn’t cheap. According to Dr. Carmalt, the average cost is $3 per pill. For a horse who needs a full pill per day (not an unusual dose), that’s just over $1,000 per year. Since your horse will need treatment for the rest of his life, that can add up—which is why some horse owners have looked to compounded versions of the drug as a less expensive option. Unfortunately, says Dr. Carmalt, the problem with these non-FDA-approved drugs is that you don’t necessarily get what’s promised. Plus, they often don’t have the same shelf-life as an approved drug—in other words, they won’t remain effective for as long.

PPID treatment is pergolide mesylate, which is sold in the U.S. under the brand name Prascend®. It is the only FDA-approved equine PPID drug in the country.

The Role of Diet

Besides medication, diet may play a role in managing the PPID horse. While a low-carb, low-sugar diets get a lot of attention, they really make the most sense if your horse also has insulin dysregulation, agree Dr. Carmalt and Dr. Frank. However, a PPID horse won’t necessarily have insulin issues, but instead could have trouble keeping weight on. Those horses would need a different nutritional approach, which is why it’s critical to work out a diet plan with your vet.

Some supplements claim to offer support for PPID horses, but Dr. Carmalt says there isn’t any solid evidence that any of them work. However, he agrees with Dr. Frank that it couldn’t hurt, and may help, to make sure your horse’s daily diet includes at least 1,000 IU of vitamin E.

“The disease involves oxidative stress, and antioxidants like vitamin E may prevent or slow the progression of PPID,” he says. “Vitamin E supplements are generally safe, so there is no harm in providing them to all horses in case this helps to prevent PPID from developing.”

In addition, he says, while there is no known PPID prevention strategy yet, obesity may be a risk factor. “There are no benefits to obesity, so horse owners are strongly encouraged to manage this problem in horses of all ages in case being obese as a young horse increases the risk of PPID developing when the horse is older,” he explains.

Some horses with PPID have trouble keeping weight on. Talk with your vet if your horse is losing weight for no apparent reason.

Ongoing Management Is Key

Horses with PPID can fare well with careful management and optimal care. What that involves depends on what symptoms your horse has and how well they’re managed with medical treatment. For instance, a horse who doesn’t shed out may need to be body clipped in warmer weather, and one who sweats excessively may need to be cold-hosed more often than the average horse.

You’ll also need to stay vigilant in watching for signs of infection and keeping up on routine care, such as dental exams, parasite control, farrier care and vaccinations. In addition, many owners opt to have their vet pull blood samples every six to 12 months to monitor hormone levels.

With good management, many horses with PPID have normal life expectancy and can return to normal athletic levels, particularly if the disease is caught early, agree Dr. Carmalt and Dr. Frank. “But patients that are more severely affected and those left untreated are likely to have a shorter lifespan,” says Dr. Frank.

In fact, the importance of early detection is a key takeaway, says Dr. Carmalt. “If you notice things that are not normal—your horse is drinking more, peeing more or not shedding—don’t just sit there and go ‘that’s odd’ for six months,” he says. “Do something about it.” By calling in your vet, you can find answers, plan a response and, if it is PPID, have the best chance for giving your horse his normal life span and keeping him at his full performance potential.

Glen Emeril: A PPID Success Story

In 2014, dressage groom and amateur rider Nicole Baergen of Wellington, Florida, took over the ride, and then ownership, of Glen Emeril, a horse she had cared for since he was imported to the U.S. from Ireland as a 5-year-old. Glennie—a chestnut Irish Sport Horse gelding—was previously trained and ridden by Heather Mason and was on the dressage high-performance track. He’d won two Horse of the Year awards and competed successfully at the Dressage Festival of Champions.

Nicole Baergen and Glen Emeril

But around the time Glennie turned 16, Baergen noticed a change. “Going into summer, he was not sweating correctly,” she says. “I’d known him forever, and he’s a beautiful sweater. He looked fine, but I knew there was something wrong.”

A vet exam led to blood tests, which showed that Glennie had PPID. No one was sure exactly what triggered the disease, but Baergen suspects that the stress of multiple climate changes in a short time period played a role. “He’d been moved from Jersey to Florida to Canada and back to Florida with the span of a year,” she says.

Working with her vet, Baergen started Glennie on one pill of Prascend® per day, a dose she’s been able to stick with ever since. She works to limit stress in his life—making it particularly helpful to have the Wellington show grounds virtually in her backyard. And she strongly emphasizes the benefits she’s seen by changing Glennie’s diet.

Baergen spent years exploring different grains until landing on her current choice, Hygain® Zero, an Australian import that’s low in carbs, starch and sugar, but has the necessary protein for a high-level athlete. She balances this with hay, soaked alfalfa pellets, and Heal and Shine Oil for skin health. She limits his access to sugar-rich grass, and the only treats she allows are a daily carrot (with Glennie’s Prascend pill hidden inside) and an apple after workouts.

Baergen credits this diet in conjunction with the medication for keeping Glennie’s PPID under control—and allowing him to continue competing at an international level. In 2018, they were doing the small tour, with multiple CDI top-two finishes, plus a reserve championship in the musical freestyle and a win in the I-1 at the Region 2 Championships.

By summer of 2020, Baergen and Glennie had qualified for the I-2 Region 3 Championships that were scheduled for October of this year and were aiming to make Glennie’s Grand Prix debut in the fall. “We’re taking our time,” she says. “But he just keeps saying, ‘Yes, let’s go!’ People look at him and can’t believe that he’s 21 or that he has Cushing’s!”

Glossary of Terms

Adrenocorticotropic hormone: A hormone produced in the pituitary gland and involved in the body’s ability to control stress. It’s measured in tests used to diagnosis PPID.

Dopamine: Produced in the brain, this chemical is used by the nervous system to help nerve cells communicate. It also helps regulate the production
of hormones by the pituitary gland. Decreased levels of dopamine are part of the chain reaction triggering PPID.

Endocrine: The system in the body that produces and secretes hormones. PPID is an endocrine (hormone-based) disease.

Hypothalamus: A region in the brain that coordinates unconscious nervous functions (like breathing) and pituitary gland activity. Its actions help to control body temperature, thirst and more.

Insulin: The hormone that manages glucose in the body (a type of sugar found in food, including grass and most grain).

Insulin dysregulation: When the body’s reaction to and production of insulin goes awry, which may put a horse at higher risk for laminitis.

Laminitis: A potentially crippling disease that is linked to insulin dysregulation.

Pars intermedia: A region of the pituitary gland that is involved in hormone production—and over-production in the case of PPID.

Pergolide mesylate: A drug that acts like dopamine in the horse’s system. In the U.S., it’s sold under the name Prascend®, the only FDA-approved drug for treating PPID in horses.

Pituitary gland: A gland located at the base of the brain that plays a key role in regulating hormones related to many body functions, such as reproduction, blood pressure, electrolyte balance and more.

Thyrotropin releasing hormone: A hormone produced by the hypothalamus that stimulates the production of other hormones. Injected in a horse with PPID, it can stimulate the release of excess stores of ACTH.

This article originally appeared in the Spring 2021 issue.






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