Pituitary Pars Intermedia Dysfunction (PPID), previously referred to as Cushing’s Disease, is an endocrine-related disease that affects approximately 20-25% of senior horses, ponies, and donkeys. 
Signs of PPID in horses include abnormal hair coats, muscle atrophy, loss of topline, poor performance, regional fat deposits, and weight loss. Horses may also experience infertility, abnormal sweating, increased thirst and urination, and immune dysfunction.
Horses affected by PPID also have a higher risk of laminitis and may experience symptoms related to insulin resistance due to concurrent Equine Metabolic Syndrome.
If you notice any of the following early warning signs of PPID in your horse, pony or donkey, consult with your veterinarian to obtain a diagnosis. Equines affected by PPID need careful feeding and management to control this condition.
What is PPID?
In healthy horses, the neurotransmitter dopamine is released by the part of the brain known as the hypothalamus to inhibit the production of hormones from the nearby pituitary gland. PPID is associated with reduced dopamine levels due to the degeneration of dopamine-producing neurons in the hypothalamus. 
Horses with Pituitary Pars Intermedia Dysfunction produce excess amounts of pituitary hormones, including adrenocorticotrophic hormone (ACTH).
Inadequate dopamine levels in PPID horses result in excess production of ACTH and other hormones, affecting various physiological systems and processes throughout the body. 
ACTH stimulates production of the stress hormone cortisol by the adrenal glands. However, despite the elevated ACTH in horses with PPID, they do not typically have high levels of cortisol in the blood. 
This may be explained by faster breakdown and clearance of cortisol in horses with PPID, such that although ACTH stimulates cortisol production, the levels in blood do not stay elevated. 
The condition most commonly occurs in older horses and can affect horses of all breeds and both sexes.
Diagnosis and Treatment
Veterinarians diagnose PPID based on blood tests and by observing clinical symptoms. Pergolide mesylate (Prascend) is the only medication licensed for the treatment of the disease.
Recognizing the signs of PPID promptly and providing treatment is essential for managing the symptoms of the condition and helping to avoid additional health complications.
Research shows that the clinical signs of PPID are often under-recognized.  The signs and symptoms of PPID can vary depending on the level of progression of the disease and the individual horse.
Top 13 Signs of PPID in Horses
1) Abnormal Coat and Delayed Shedding
One of the most common clinical signs of PPID in horses, ponies and donkeys is hair and coat abnormalities.
Horses with PPID may grow an excessive coat of hair (hypertrichosis) due to more hair follicles remaining in an active growth phase than in a resting phase. The coat may also fail to shed normally with seasonal changes.
The underlying cause of hypertrichosis is unknown. However, researchers have proposed it may relate to the pressure of an enlarged pituitary gland on the brain’s thermoregulation centres or the overproduction of α-melanocyte-stimulating hormone (α-MSH) by the pituitary gland. 
Hair and coat abnormalities may be subtle and only occur on specific regions of the body, including the base of the neck, jawline, and backs and fronts of the front and rear legs in the early stage of the disease. The summer coat may be a lighter shade and grow longer than normal in these areas.
Coat abnormalities may be more noticeable and cover larger areas of the body in horses with advanced PPID. Their winter coat may not shed out until late into the spring or summer.
In some horses with advanced PPID, the winter coat fails to shed. Advanced PPID can cause the entire coat to be much longer than normal and or curly.
A research review on horses with PPID found that 69.9% had hypertrichosis. 
Laminitis describes inflammation of layers of tissue inside the hoof called laminae and is very painful and debilitating for affected horses.
In severe cases, laminitis can lead to failure of the hoof laminae, which causes the pedal bone to shift orientation within the hoof capsule and possibly penetrate the sole.
Common signs of laminitis include:
- Strong digital pulse in the lower limbs of affected hooves
- Warmth in affected hooves
- A shortened stride or stiff gait
- Hoof deformities including abnormal growth rings
- A visible white line between the hoof wall and sole
- Shifting weight from hoof to hoof
- Reluctance or refusal to pick up the feet or move
- An abnormal stance in which the horse leans too forward or backward
Research indicates an association between laminitis and insulin dysregulation. In experimental settings, laminitis has been induced via the administration of insulin. 
A study of 325 horses with PPID determined that 32% had high non-fasting insulin levels, and 66% of this group had laminitis. 
The specific cause of laminitis in PPID-affected horses is hyperinsulinemia. However, high cortisol also alters the vascular response to the normal vasodilating effect of insulin. 
Laminitis occurring in the fall, when ACTH is further elevated, can be the first sign of PPID in early cases.
3) Muscle Wasting and Loss of Topline
Muscle atrophy (a loss of muscle mass) occurs in approximately 50% of horses with PPID.  Older horses with the condition show clinical signs of muscle wasting more frequently than younger horses. 
Muscle loss in horses with PPID commonly occurs in the topline muscles near the spine (epaxial muscles). Loss of muscle may cause the appearance of sunken shoulders and prominent withers, spine, and hip bones.
Types 2A and 2B muscle fibres have been shown to atrophy in horses with PPID. It is unknown if muscle atrophy occurs due to an increase in muscle breakdown or a decrease in muscle protein synthesis. 
4) Lethargy and Decreased Athletic Performance
Horses with PPID may exhibit decreased energy or diminished athletic performance compared to horses without the condition.
Lethargy is observed in 4 to 95% of horses with PPID. Older horses with PPID are more commonly affected by lethargy compared to younger horses with the condition. 
Lethargy associated with PPID may result from increased concentrations of beta-Endorphins (β-END) in the body.  β-Endorphins are short chains of amino acids (peptides) that exert various physiological effects, including promoting relaxation. 
If laminitis is present in a horse with PPID, a reluctance to move due to pain could be mistaken for lethargy.
5) Fat Deposits
Horses affected by PPID may have concurrent Equine Metabolic Syndrome (EMS), a condition that involves hyperinsulinemia.
EMS often occurs in senior horses affected by PPID and could be a predisposing factor for the condition. The exact cause of EMS is unknown, although genetics, environment, diet, exercise, and the gut microbiome may influence the development of the condition. 
EMS can result in abnormal fat deposition on the body and localized areas of fat under the skin, known as regional adiposity. Fat deposits may occur on the crest of the neck (cresty neck) and head of the tail, behind the shoulders, around the mammary glands in mares, and on the prepuce in geldings.
6) Weight Loss
Horses with PPID may be affected by weight loss. This sign of PPID is often easily recognized by owners.
The prevalence of weight loss in horses with PPID ranges between 5 and 88%, according to research studies.  Older horses with PPID are more likely to experience weight loss than younger horses with the condition.
The physiological causes of weight loss in horses with PPID are unknown. However, loss of muscle mass, which contributes to overall weight loss, is known to occur in horses with PPID.
7) Abnormal Sweating
Horses with PPID may exhibit abnormal sweating patterns, including overproduction of sweat (hyperhidrosis) and an inability to sweat (anhidrosis).
Horses with PPID that live in warmer and more humid climates and closer to the equator are more likely to have hyperhidrosis. Horses with PPID that are living in cooler, more temperate climates are more likely to have anhidrosis. 
However, PPID horses may develop either condition without respect to the climate, e.g. inappropriate sweating in winter.
Hyperhidrosis in PPID horses is believed to result from hypertrichosis (excessive hair growth). However, some horses with PPID may still sweat excessively despite living in cool climates or when their entire body is clipped. 
Anhidrosis occurs when sweat glands become exhausted. This condition can cause exercise intolerance and potentially death as thermoregulation is compromised. 
The specific causes of abnormal sweating in horses with PPID are unknown.
8) Increased Thirst and Urination
Excessive drinking (polydipsia) and urinating (polyuria) can occur in horses with PPID.
The exact cause of polyuria and polydipsia in horses with PPID is unknown. However, researchers have proposed that these conditions result from reduced secretion of antidiuretic hormone (ADH) from the pituitary gland. 
It has also been suggested that horses with PPID may have polydipsia due to increased thirst following excessive sweating and fluid loss. 
9) Immune Disfunction
Horses with PPID may have impaired immune function and an increased risk of opportunistic infections. One study found that opportunistic infections were present in 35% (63 out of 180) of horses with PPID but only 11% (4 of 33) of non-PPID horses. 
- Abnormal functioning of white blood cells of the immune system
- Alterations in cell signalling molecules which regulate acute inflammatory responses
- Elevated ACTH levels and higher cortisol production
10) Neurological Problems
More research is needed to determine the prevalence of neurological abnormalities in horses with PPID.
Ataxia (weakness/inconsistent gait), blindness, seizures and narcolepsy are some neurological signs that have been associated with advanced PPID. 
Neurological abnormalities in PPID horses are believed to occur due to a benign tumor (macroadenoma) of the pituitary gland. This can be diagnosed by your veterinarian using computed tomography scan (CT scan). 
11) Suspensory Ligament Atrophy
Suspensory ligament degeneration is recognized in older horses and those with PPID.
- Abnormally arranged collagen fibres
- Inclusions of cartilage
- Bleeding from ruptured blood vessels (hemorrhage)
- Accumulation of a protein called proteoglycan between fibres, which weakens the tissue
Studies suggest that dysregulated cortisol metabolism within specific tissues may contribute to the degeneration of suspensory ligaments in horses with PPID. 
Compared to healthy horses, there are more glucocorticoid receptors (receptors to which cortisol and other steroid hormones bind) in suspensory ligament samples of PPID horses. 
Connective tissue that is exposed to excess steroid hormones and glucocorticoids, including cortisol, can have inhibited cellular growth, regeneration, and repair.
Mares with PPID may have abnormal or nonexistent reproductive cycles, resulting in infertility.
A study of 67 thoroughbred mares determined that the reproductive performance of mares with high ACTH levels was significantly lower than those with low ACTH levels.
High ACTH levels may promote the abnormal secretion of various reproductive hormones, including cortisol, which can interfere with conception and delivery. 
This study also noted a higher prevalence of injured vaginal and external uterine tissues in mares with high ACTH levels.
Diagnosing infertile mares by assessing health factors, including ACTH concentration, and providing any necessary treatment may help to improve their reproductive performance.
13) Insulin Resistance
Approximately 30% of horses with PPID have high blood insulin levels (associated with EMS) because their tissues are less sensitive to this hormone. 
In healthy horses, insulin regulates sugar metabolism by signalling tissues to take in glucose (sugar) from the bloodstream. It also stimulates tissues to utilize glucose to produce glycogen, a form of energy stored in cells.
In horses with insulin resistance, the tissues fail to respond appropriately to insulin, and cells cannot take up as much glucose from the blood. As a result, the body must produce more insulin to keep glucose normal. Horses with PPID are more likely than horses with only EMS to progress to type 2 diabetes with high blood glucose. 
Insulin resistance can be confirmed by measuring insulin concentrations in the blood. Insulin resistance is diagnosed in horses with elevated levels of this hormone over a period of time or when there is an abnormal insulin response after eating a meal or an oral sugar test (glucose challenge). 
Clinical signs of insulin resistance explain many of the symptoms of PPID, such as the accumulation of fatty deposits on the neck, top of the tail, shoulders, and mammary glands, and laminitis. 
Horses with PPID should be tested for concurrent insulin resistance to avoid related health complications, including laminitis.
If your horse shows any of these warning signs for PPID, consult with your veterinarian to obtain an accurate diagnosis. Horses displaying symptoms of metabolic syndrome may have PPID that needs to be treated with medication.
Early detection and intervention are important for controlling the symptoms of PPID and preventing serious health complications, such as laminitis.
If your horse is diagnosed with PPID, ask your veterinarian whether they are a candidate for the drug Prascend. You can also adopt feeding and management changes to support your horse’s metabolic health and reduce the risk of adverse outcomes.
Work with a qualified equine nutritionist to help you formulate a balanced feeding program that supports your horse’s insulin sensitivity, immune system, muscle mass and overall well-being.
Is Your Horse's Diet Missing Anything?
Identify gaps in your horse's nutrition program to optimize their well-being.
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