Thank you to Boehringer-Ingelheim for this Update on PPID (Equine Cushing’s Disease) for Horse Owners
FIRST, WHAT IS PPID?
Pituitary Pars Intermedia Dysfunction (PPID), also known as Equine Cushing’s Disease, is the most common endocrine disorder in horses. An estimated 21% of horses and ponies over the age of 15 are affected by this disease.1 PPID is a chronic progressive disease. PPID causes multiple health problems for the horse, including laminitis and recurrent infections.
HOW DOES PPID OCCUR?
The pituitary gland is located at the base of the brain. As PPID horses age, dopamine-secreting neurons that control the pituitary degenerate at a faster rate. The exact cause of this degeneration is poorly understood, but is thought to result from oxidative damage, similar to human Parkinsons disease.2 When degeneration of neurons occurs, the pituitary becomes abnormally active, increasing secretion of hormones which result in the individual clinical signs of PPID (below.)
WHAT DOES PPID LOOK LIKE?
Most horses affected with PPID are between 15-21 years of age, although horses as young as 4 have been reported. Ponies and Morgans are overrepresented.3 Horses with a history of Equine Metabolic Syndrome (EMS) are thought to be at higher risk.3 PPID-affected horses show a wide variety of nonspecific clinical signs which worsen over time.
Early signs of PPID may include:
- Abnormal haircoat (delayed shedding compared to herdmates, dull, coarse, thicker haircoat, change in hair color, presence of longer, lighter hairs along the jaw, neck, elbow, lower legs)
- A shift in metabolism from an “easy keeper” to more lean body condition
- Regional fat deposits, i.e. “cresty neck”
- Poor performance, attitude/behavioral changes, i.e. “dullness, lack of energy”
- Subfertility
- Unexplained laminitis episodes,“foot soreness”
Advanced signs of PPID may include:
- Generalized long, curly, dull haircoat that fails to shed despite change in season
- Muscle wasting with regional fat deposits, “pot-bellied appearance”
- Increased thirst and urination
- Recurrent infections, i.e. white line disease, hoof abscesses, sinusitis
- Inappropriate sweating (not sweating or excessive sweating)
- Chronic laminitis
- Neurologic deficits/blindness
Signs of PPID may be erroneously attributed to the normal ageing process. Subtle alterations in length, color, texture, or thickness of hair may indicate early PPID. Owners should also record when their ageing horse sheds its winter haircoat and compare this time with herdmates to detect delayed shedding. Chronic, recurrent infections (white line disease, hoof abscesses, sinus infections, skin infections, etc.) that fail to respond to treatment may occur in PPID due to immunosuppression. Another indicator of PPID may be subtle foot soreness. Foot soreness may be difficult to recognize unless the horse is examined on a hard surface. Subtle foot soreness without an inciting cause can indicate the presence of chronic laminitis, which can become debilitating. The author has also encountered several reports of confirming PPID in horses with a history of excessive sweating, or alternatively, failure to sweat. The presence of a generalized long, curly, dull haircoat that fails to shed is easily recognized and considered pathgnomonic for PPID. However, the presence of this “wooly mammoth” haircoat indicates advanced disease. Ideally, detection and treatment of PPID should begin long before this classic sign is observed. The diagnosis of PPID may be missed altogether due to focus on the primary problem (i.e. infection, failure to sweat) and lack of other overt signs.
COMPLICATING FACTORS?
High blood insulin with insulin resistance (IR) now collectively referred to as insulin dysregulation,3 is a common finding in approximately 30% of PPID horses.Insulin works within the body to mediate absorption of glucose into tissues such as liver, adipose, and skeletal muscle. The concern with insulin dysregulation is that certain tissues can be deprived of proper nutrients. Tissues within the hoof are extremely sensitive to changes in nutrient supply, and horses with a history of insulin dysregulation usually suffer from laminitis. Insulin dysregulation occurs in a minority of horses with PPID, but is a defining component of Equine Metabolic Syndrome (EMS.)
HOW IS PPID DIAGNOSED?
Diagnosis of PPID can be challenging. As of this writing (July 2013), a diagnosis of PPID emphasizes one screening Tier 1 blood test, resting ACTH, or another dynamic Tier 1 blood test, TRH Stimulation measuring ACTH. TRH measuring ACTH may be used when ACTH is inconclusive or to confirm a positive or negative result. Discuss these tests with your veterinarian to initiate the best diagnostic plan.
Detection of early PPID remains difficult, although this is the time period in which medical intervention is most satisfying. Unlike screening ACTH, TRH w/ACTH is showing potential for detection of earlier PPID.3 However, in horses with negative or “grey area” initial test results, tests should be repeated in 6 months or another Tier 1 test used. If test results remain negative in light of clinical signs, a 6-month treatment “trial” with pergolide (Prascend®) can be considered. PPID tests are affected by season, and should always be interpreted alongside clinical signs. In advanced disease, the presence of the classic “wooly mammoth” haircoat remains the most sensitive indicator of an abnormally functioning pituitary, although with advanced disease, medical treatment is palliative.
It is also recommended that when screening for PPID, insulin status should also be evaluated for assessment of laminitis risk. Insulin, leptin, and triglcyerides may also be measured as part of a comprehensive “panel” in horses with a history of obesity. As the relationship between EMS and PPID is emerging, a complete diagnostic evaluation should include testing parameters for both disorders.
HOW IS PPID TREATED?
PPID is a chronic, lifelong condition for which there is no cure. Treatment of PPID focuses on administration of pergolide and attention to other significant issues, such as laminitis, dental disease, and maintenance of proper diet. Pergolide is the gold standard for treatment of PPID. Pergolide acts to restore dopamine to the pituitary, controlling its activity, and decreasing the production of detrimental hormones. Until 2011, only compounded pergolide was available. Compounded pergolide products have demonstrated rapid declines in potency and stability over time.4 In one recent study on compounded pergolide, a high degree of variation was found “between two containers of same product ordered from same pharmacy on the same date.”4 In 2011, FDA-approved pergolide became available as Prascend® 
(www.prascend.com.) Prascend® is now the treatment of choice for PPID.5 Owners should expect significant improvement in their horse’s clinical signs and test results when properly controlled with pergolide. However, similar to human Parkinsons, it should be expected that PPID will progress over time. Some horses with advanced PPID can be managed with higher doses of pergolide, with the addition of cyproheptadine. Pergolide, however, has not been conclusively shown to improve insulin parameters, therefore management of laminitis due to insulin dysregulation should be primarily addressed with diet, exercise, +/- medical therapies. Two recent studies do demonstrate a beneficial effect of pergolide on certain insulin parameters and body weight, although this remains a subject of ongoing investigation.6,7 Although PPID is managed medically, body clipping, farrier care, regular deworming, and routine dentistry are of equal importance. Additional water should be provided if the horse drinks and urinates excessively.
TAKE HOME:
The determination of whether an ageing horse is suffering from PPID is imperative to overall care. With awareness of subtle clinical signs, owners and veterinarians can work together as a team to identify this progressive disease. And by intervening earlier with treatment and control strategies, we can provide our horses with the optimal chance at maintaining healthier, more productive lives.
AUTHOR:
Marian G. Little, DVM, Field Equine Professional Services, Boehringer Ingelheim, Paris, KY
Inquiries via email: marian.little@boehringer-ingelheim.com
REFERENCES:
1McGowan TW, Pinchbeck GP, McGowan CM. Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses. Equine Vet J 2013;45:74-79.
2McFarlane D, Cribb AE. Systemic and pituitary pars intermedia antioxidant capacity associated with pars intermedia oxidative stress and dysfunction in horses. Am J Vet Res 2005;66:2065-2072.
3Frank N. Pituitary Pars Intermedia Dysfunction. Current Therapy 2013. Pending publication.
4Stanley SD,Knych HD. DVM, Ph.D. Comparison of Pharmaceutical Equivalence for Compounded Preparations of Pergolide Mesylate. AAEP Proceedings 2012; 56: 274-276.
5PRASCEND® (pergolide mesylate) [Freedom of Information Summary]. St. Joseph, MO: Boehringer Ingelheim Vetmedica, Inc.; 2011.
6Durham A, Campbell J. Changes in Resting Serum Insulin Concentrations Following Pergolide Treatment in Horses with PPID. Equine Endocrinology SIG. ACVIM, Seattle, WA. 2013.
7McFarlane D, Banse HE. Response of Serum Insulin, Oral Sugar Testing and Body Weight in Horses Treated with Prascend.® Equine Endocrinology SIG. ACVIM, Seattle, WA, 2013.