Cushing’s Disease: A Slow, Silent, Formidable Foe

Pinning down a diagnosis can take multiple tests and repeats.
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Pinning down a diagnosis can take multiple tests and repeats.
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Each year, the hands of time cause subtle differences in our magnificent equine companions. Some changes, like the ones that come from experience and wisdom, are good. These bring serenity.

But, with these improvements, come physical signs that remind us our horses are aging. Their joints become stiff and strides short. Everything takes longer: warming up, cooling down, shedding out, getting fit, and coming sound. Where there was once muscle, there now is not. But, because this happens slowly, we assume these are normal signs of aging. Or are they?

What if the vet told you those “signs of aging” aren’t that at all? What if they were a disease process? What if that disease could be easily non-invasively diagnosed and managed, somewhat turning back those hands of time? Such is the case with equine Cushing’s disease.

What is Cushing’s Disease?The name "Cushing's disease" comes from human medicine, crossing over into the horse world because horses with this condition show physical ("clinical") signs similar to those of human beings with Cushing's. However, the two disease processes are distinctly different. While both involve dysfunction of the pituitary gland, a gland found at the base of the brain, human Cushing’s disease affects a different part of the gland in contrast to equine Cushing's disease. Because of the difference between the physiologic processes, equine Cushing’s disease is now officially termed "Pituitary Pars Intermedia Dysfunction" (or PPID) in the veterinary community.

Situated deep near the brainstem, the hypothalamus regulates many functions in the body. Among the more relevant functions to this disorder, the hypothalamus allows the nervous system to communicate with the endocrine system.

Hormones are powerful chemicals that can illicit physiologic changes that govern everything from appetite, to fatigue, to sex drive. For all intents and purposes, the hypothalamus functions as a “puppet master” to the anterior pituitary gland, which sits just beneath it deep in the brain.

The pituitary gland is like Grand Central Station for our hormones. Many hormones are produced by it, including beta-endorphin, which relaxes us; alpha-melanocyte stimulating hormone (MSH), which causes skin pigmentation; and adrenocorticotropic hormone (ACTH), which stimulates our adrenal glands. You know the adrenal glands—they sit next to the kidneys and secrete cortisol, a stress hormone we’re all familiar with. 

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Whoa! No brakes!The hypothalamus is responsible for putting the brakes on the anterior pituitary gland through a series of nerve fibers that connect the two. The nerve fibers release an inhibitory neurotransmitter called dopamine, which tells the anterior pituitary to “calm down, stop producing hormones.” 

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Horses with PPID have a diminished capacity to send and receive that dopamine signal due to neurodegeneration (decaying of the nerves) between the hypothalamus and the anterior pituitary. Hence, horses with PPID will have enlarged anterior pituitary glands. 

Often, swollen pituitaries are referred to as pituitary adenoma, which makes one think of a cancerous tumor. It is a tumor, but a benign one. It occurs because the gland has nothing to keep it in check, so it just grows and secretes too much hormone. 

When the anterior pituitary is left to run wild in the absence of adequate dopamine, several downstream physiologic consequences occur. For instance, too much beta-endorphin causes the horse to become tired and lackadaisical. 

Alpha-MSH contributes to the horse’s obesity and may play a role in excessive hair growth and failure to shed. At the same time, too much ACTH causes an excess level of circulating cortisol.

Cortisol is powerful. It puts stress on the liver to produce sugar, which results in a high circulating blood concentration of sugar. It also suppresses the production of white and red blood cells, which can result in anemia (no red blood cells) and leukopenia (no white blood cells).

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Red blood cells carry oxygen throughout the body. White blood cells are defenders in the immune system. Without enough of them, the body is immune suppressed, which means, for example, wounds won’t heal as fast, parasites may be more of a problem, and internal infections like pigeon fever (see October 2012) are more likely.

All of that cortisol and circulating blood sugar also has a deleterious effect on the lamina in the feet, which predisposes the horse to laminitis. The cortisol causes abnormal fat deposition and escess hair growth all over the body. 

The more common physical signs of PPID include:

  • Lethargy.
  • Loss of muscle mass/weight.Abnormal fat deposition on the crest of the neck, at the base of the tail, in the sheath area, and in the fossa (“indentation”) above the eye. NOTE: “Abnormal fat deposition” does not mean obesity!
  • Long hairy coat that fails to shed out in spring. Hair can be coarse and “wirey,” sometimes curly, and most commonly grows under the jaw, on the backs of the legs and on the under belly in early stages. In more advanced stages of the disease, abnormal hair growth and shedding is sudden and quick.
  • Polyuria (excessive urine).
  • Polydypsia (excessive drinking).
  • Ravenous appetite.
  • Impaired wound healing.
  • Laminitis.
  • Pot-bellied appearance.

Not all signs need to be present for a horse to have PPID. And sometimes there are no outward signs. Sometimes, the disease is detected on routine blood testing.

Getting Lost in a Diagnosis. Laminitis. Fatigue. Abnormal fat deposition. Sound familiar? That’s because other diseases present the same clinical signs. Both equine metabolic syndrome and hypothyroidism (see August 2013) can present with similar signs.

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None of the available tests for diagnosing PPID are perfect. All can result in false negative and false positive results on occasion and have drawbacks.

  • The dexamethasone suppression test can cause laminitis and requires two vet visits. Once considered the gold standard for diagnosing PPID, we now know it produces widely varying results. This, coupled with the added logistical parameters and the risk of laminitis, made it lose popularity among veterinarians. 
  • The thyrotropin releasing hormone stimulation test (TRH test) is poorly developed and not widely available. Horses with PPID will show an increase in circulating levels of blood cortisol after they’re given a dose of thyrotropin releasing hormone. 
  • The Endogenous ACTH test has become more accurate over the years and is relatively inexpensive and non-invasive (there are virtually no risks and it just involves the vet drawing 1 or 2 cc of blood). However, that recent research has shown that the results of the test vary depending on the time of year (see chart on p. 1). 

Sometimes, pinning down a diagnosis takes multiple tests, either of different types or by repeating the same test on multiple occasions. Some choose to forego testing and simply try a three-month trial of the drug pergolide instead. Generally, if pergolide is given as a way of “backing into a diagnosis,” horses that are positive for PPID will show increased energy, less drinking and urination, and changes in their hair coat/shedding pattern.

Managing PPID: A Key Factor. Management strategies coupled with medication have dramatically prolonged and improved the lives of horses suffering with PPID. By far and away, the administration of pergolide will go the furthest to helping a horse with PPID. However, sometimes pergolide is not enough. Our chart below includes suggested medications to help manage PPID.

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Beyond that, Cushingoid horses require additional management:

Because of immune suppression, they’re prone to tooth root abscesses, hoof abscesses, pneumonia, and other infection. Therefore, routine dental work (at least annually) and optimal hoof care (trimming +/- shoes) every six to eight weeks will greatly reduce the chances of abscesses. As always, if their living areas can be packed with base rock to avoid standing in mud, this will help hoof health as well.

Another “good habit” to practice is the use of an anti-thrush treatment bi-weekly at the least during the wet season. We recommend Horseshoer’s Secret, D-Thrush, Thrush-XX, Thrush Stop, and White Lightning.

Owners must keep a watchful eye on horses with PPID. At the first sign of trouble, there needs to be intervention. If the horse isn’t eating, take his temperature. Anything above 101°F should be reported to the veterinarian. Routinely smell the air that the horse breaths out of its nostrils. If it smells foul, it could be a tooth root abscess. If a horse goes off feed, call the vet. It’s important that a physical exam and blood work be done to make sure that infection isn’t taking hold.

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Feed a low-carb diet. See January 2013.

Some horses with PPID require a special low-carb, highly digestible, high-energy diet. In many cases, especially in the presence of bad teeth, this diet takes the form of pellets. Pelleted diets assist with the reversal of weight loss and muscle wasting seen in PPID horses.

Horses with PPID are more susceptible to parasite infestation. Therefore, keeping their environment clean through a vigorous manure-management program as well as use of a dewormer on a routine basis are recommended. When deworming, it’s important to ensure that the horse receives an adequate dose, and at an effective interval for your given environment.

Body clip that coat! Horses with PPID often will have to be body clipped between two and four times per year, even in the summer. All of that shaggy hair makes them uncomfortable. Invest in a good pair of body clippers and have at it (see January 2013 and April 2012). 

Along those lines, horses with PPID will need to be blanketed during cold weather. Remember, their bodies are under stress, so anything you can do to help reduce external stresses (such as cold weather) will help them.

Light exercise or unrestricted turnout is also helpful for circulation, weight control, metabolism, and joint health. 

Bottom Line. Managing Cushing’s disease is not a job for the weary. Fortunately, thanks to the advancements made in Cushing’s research, your PPID horse can enjoy a longer, productive life.

Article by Contributing Veterinary Editor Grant Miller DVM.