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First Posted: May 2007
Dec 29, 2015

Equine Cushing's Disease or Pituitary Pars Intermedia Dysfunction (PPID)

by Debora Johnson

Note: "...Obtaining an accurate PPID diagnosis is key to managing the disease. While no test is 100% accurate, it's important that a veterinarian try to pin down a diagnosis before medicating a horse. A variety of tests are available for diagnosing PPID, though most veterinarians currently rely on ACTH testing. Scientists are working on validating a few other assays, which eventually might prove more sensitive and specific for detecting Cushing's disease." Testing for Equine Cushing's Disease

PPID occurs in 15-30% of horses and ponies more than 20 years old. Veterinarians have determined that certain equid types, such as Morgans and pony breeds, are predisposed to developing the condition, and their risk only increases with age. What is PPID? It is a slowly progressive disease that can take years to show clinical signs. Changes may begin in a horse's midlife or early teens. "Cushing's disease (also known as Cushing disease, tertiary or secondary hypercortisolism, tertiary or secondary hypercorticism, Itsenko-Cushing disease) is a cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary (secondary hypercortisolism). This is most often as a result of a pituitary adenoma (specifically pituitary basophilism) or due to excess production of hypothalamus CRH (Corticotropin releasing hormone) (tertiary hypercortisolism/hypercorticism) that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids." Cushing's Disease

Updates: Study/Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses

Excellent Article-Read--Spring is almost here! Grass Founder "Older horses and ponies may be prone to grass founder (pasture-associated laminitis), particularly in the early spring when grasses contain a higher concentration of sugar. Horses suffering from equine metabolic syndrome (EMS) or Cushing's disease (also known as pituitary pars intermedia dysfunction, or PPID) are especially susceptible. Pastures high in Non-Structural Carbohydrates (NSCs) are more likely to provoke laminitis. NSCs include fructan, sugar and starch. Fructan is the most commonly-implicated NSC with regard to inducing laminitis, although similar environmental conditions can create high concentrations of all carbohydrate forms. ..."

Table Topic: Cushing's or Metabolic Syndrome?
Autumn Brings Challenges to Cushings Diagnosis Management
James M. Casey, D.V.M., M.S. on Cushing's Disease

Research: The use of adrenocorticotrophic hormone as a potential biomarker of pituitary pars intermedia dysfunction in horses.

  • ACTH levels were significantly higher in horses with Cushing's disease than in the healthy horses over a 24-hour period;
  • ACTH concentrations were significantly higher in September and December than in March and June in all horses;
  • Fluctuations in ACTH levels were larger in horses with Cushing's compared to normal horses.

What Causes Equine Cushing's Disease?

A tumor in the pituitary gland can cause Cushing's Disease in the horse as well as an imbalance in the adrenals (hyperadrenocorticism). The production and regulation of hormones is the function of the pituitary gland. The tumor is usually benign, but it creates an imbalance of hormones in the horse's body. Excess hormones are produced. To date, the cause of the tumor itself is not known. Certain breeds of horse seem to be more prone to Cushing's Disease. Morgans and ponies have a higher predisposition. Cushing's has no favorite gender. Aged horses are more prone to the disease.

Symptoms

  

A thick, long, shaggy, matted coat of hair is the most noticeable symptom of Cushing's Disease in the equine. Horses with Cushing's do not shed out in the spring. Often they still have their coats well into the summer months. If there is excessive drinking, urination, recurring foot abscesses, loss of muscle tone and mass predominantly along the topline and rump (polydipsic and polyphagic), or laminitis there is may be an imbalance in the adrenal gland. They may also become immosuppressed and become subject to a variety of parasitic diseases, infectious agents such as helminthiasis or pneumonia. Diabetes mellitus (sugar diabetes) or diabetes insipidus may also be a symptom. The horse's eyes may appear protuberant because of the deposit of fat in the supra-orbital area. Horse's with Cushing's Disease tend to sweat more. There is often a weight loss despite an increased appetite. Their body changes shape. They look "ribby" and "blocky." They become depressed, have dull eyes, lose shine in their coat, and generally look unwell.

Testing for Cushing's Disease

An overnight dexa-methasone suppression test is done. What is this? The dexamethasone suppression test, or DST, requires that the horse give a small sample of blood, then be administered cortisone, and a follow-up blood sample be taken the next day. The blood samples are then compared to determine the horse's response to excess cortisone.

Treatments

If your horse's blood tests indicate a diagnosis of Cushing's Disease there are several treatments available that may improve your horse's condition. Pergolide or cyproheptadine are the two most commonly used drugs that have shown positive results in combating the effects of Cushing's disease. In a test conducted at Michigan State University by Dr. Schott (late 1996-2001) it was concluded that horse's treated with pergolide was the preferred treatment. A controlled study was done which compared horse's treated with pergolide, with cypropeptadine, and no treatment. They found that the dexamethasone (DST) tests often returned to normal. When treated with pergolide 75% of horses are expected to improve. Treatment is expensive and requires that the drug be administered daily. Follow-ups by the vet for blood work are imperative. If treatment is stopped the symptoms will reappear within several weeks.

When deciding whether to medicate a horse with Cushing's disease, you should first consider the cost and the condition of the horse in question. Horses with relatively mild symptoms generally respond best to medication, which may extend their useful lives by a number of years. However, a horse that is already suffering from chronic founder/laminitis and recurrent infections as a result of immune system failure will likely derive very little benefit. It is worth remembering that, while these drugs treat the symptoms, they do not treat the pituitary tumor itself. They merely treat the symptoms, and the tumor will continue to grow until it compromises the horse's quality of life. There are currently no methods of removing or curbing the growth of equine pituitary adenomas.

Cyproheptadine (Periactin®)

This seratonin blocker is available in tablet form, which is easily absorbed into the horse's system. A veterinarian will normally start a horse at a specific dose level (usually about 0.13 mg/kg, or about 58 mg for an average 440 kg horse), and increase it until you the clinical signs of Cushing's disease begin to improve.

The simplest way to gauge improvement is by monitoring the horse's water intake over a 24-hour period. This is best achieved by keeping the horse stabled and provided with water in a bucket. The dosage of medication is slowly increased until the horse's water intake returns to normal levels (usually taking about six to eight weeks). During this time, you will likely notice that other symptoms of Cushing's disease , such as the heavy coat and pot belly, also disappear, and the horse regains vigour and muscle tone. After this level of improvement has continued for a month, the dosage of cyproheptadine is gradually reduced until a maintenance level is reached.

Cyproheptadine is effective in about 75 - 80 percent of cases.

Pergolide mesylate (Permax®)

This drug was originally used to treat human Parkinson's disease. At the doses considered successful in treating Cushing's disease, however, pergolide mesylate had a severe vasoconstricting effect that served to worsen the chronic laminitis that frequently accompanies Cushing's disease. In the early '90s, Montana equine veterinarian, Dr. Duncan Peters, decided to give a very small dose of the drug to a horse suffering from Cushing's disease. This dose was roughly equivalent to one-sixth of the amount considered appropriate for a human. The horse responded positively. In a further study, Dr. Peters was able to duplicate the positive results in eight of nine horses/ponies with no negative side effects.

The average response time was close to three weeks, and improvement continued until the horses stabilized at an average 21 weeks. Since these results were published, pergolide mesylate has become an acceptable treatment option for Cushing's disease.

Pergolide mesylate is usually administered orally, in tablet form. (Crushing the tablets with a little molasses is an effective way to dose your horse.)

Bromocriptine mesylate (Parlodel®) is a less popular drug used to treat equine Cushing's disease, although still used by some veterinarians. Problems in absorption are often documented and the drug purportedly produces a number of side effects.

Herbal treatments

While the jury is still out of the efficacy of herbal treatments for Cushing's syndrome, there is indication that chaste berry (Vitex agnus castus) may be effective for early stage cases of Cushing's syndrome. The UK Horse Journal ran a field trial of Vitex including 10 horses and ponies. The subjects were aged between 13 and 25 years, and were either diagnosed with Cushing's disease or demonstrating the classical Cushing's symptoms.

The Journal reported that typical response was "rapid and dramatic." Shedding would typically begin within three weeks, and energy level quickly increased. High blood glucose and insulin levels dropped in some cases within four to six weeks. (The results of a later study at the University of Pennsylvania's New Bolton Center repudiated these claims. Nonetheless, some horse owners feel that their horse was helped through use of the herb)

Always consult your veterinarian before starting any type of treatment for your horse, including herbal remedies.

For More Information:

Researchers Evaluate Steps for Diagnosing Cushing's Disease
Biomarkers for Cushing's Disease in Horses
What Causes Equine Cushing's Disease?

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