Pituitary Pars Intermedia Dysfunction (PPID) is an endocrine-related disease that commonly affects older horses of all breeds. Twenty percent of senior horses, ponies, and donkeys are believed to have PPID.

The condition results in an overproduction of pituitary hormones, causing metabolic dysfunction. Horses with PPID may also have insulin resistance and an increased risk of laminitis.

Typical clinical symptoms of PPID include abnormal coat condition with delayed shedding, muscle loss, impaired immune function, and behavioural changes.

PPID is diagnosed by your veterinarian with tests and observation of clinical symptoms. Pergolide mesylate (Prascend) is the only medication licensed for the treatment of the disease.

Appropriate management of horses with PPID involves diet, exercise, regular veterinary care, and consistent monitoring of hormone levels. If your horse has PPID, submit their diet online for a free evaluation by our equine nutritionists.

What is PPID?

Pituitary Pars Intermedia Dysfunction is a common equine endocrine disorder, primarily afflicting horses over the age of 15, and becoming more likely to develop as the horse ages. [1]

It involves an excessive production of hormones, such as adrenocorticotrophic hormone (ACTH), from the pars intermedia lobe of the pituitary gland located at the base of the brain.

The level of hormones in the pars intermedia of a horse with PPID can be 100 times higher than in a healthy horse.

The overproduction of hormones is caused by degeneration of the dopamine-producing neurons in the hypothalamus, potentially due to oxidative stress. Low dopamine levels impair the normal regulatory function that shuts off the production of pituitary hormones.

PPID is an age-related disease; aging is the only major risk factor for the condition, although horses as young as 7 years of age have been diagnosed. Breed and sex do not predispose horses to develop the disease.

Epidemiologic studies estimate that 20% of horses over the age of 20 are affected by PPID, and 30% of those over 30 are affected. [3]

Although previously referred to as Equine Cushing’s Disease, this title is now considered inaccurate. Cushing’s Disease in humans affects a different location within the pituitary gland. [2]

How Does PPID Affect Horses?

The equine pituitary gland consists of 3 lobes including the pars distalis, pars intermedia, and pars nervosa. PPID affects the pars intermedia part of the gland.

The hypothalamus, a part of the brain, controls the release of hormones from the pituitary gland. This gland plays a key role in regulating hormones related to metabolism and affects the function of various organs.

PPID results in an overproduction of multiple hormones that cause an abnormal metabolic state. Increased levels of these hormones affect various processes throughout the body.

In healthy horses, the neurotransmitter dopamine is released by the hypothalamus to inhibit the production of hormones by the pars intermedia. Dopamine binds to receptors on the surface of cells to turn off the secretion of hormones from this part of the pituitary gland.

PPID results from the degeneration of dopamine-producing neurons in the hypothalamus. This prevents the hypothalamus from regulating the release of hormones by the pituitary gland, such as adrenocorticotrophic hormone (ACTH).

Horses with PPID have high levels of circulating ACTH, triggering the adrenal gland to increase production of the stress hormone cortisol. Higher cortisol levels lead to insulin resistance.

Low dopamine also causes the pituitary gland to increase in size as the cells of the pars intermedia divide and enlarge. Horses with PPID may develop benign tumours in this part of the gland.

The expansion of the pars intermedia can cause other lobes of the pituitary and the hypothalamus to become compressed. This may cause a loss of function in these structures and result in a range of clinical symptoms.

Symptoms of PPID

Research shows that the clinical signs of PPID are often under-recognized. [4]

PPID can cause a range of symptoms depending on the severity of the condition. [5] Early symptoms include:

  • Decreased athletic performance
  • Changes in attitude
  • Delayed shedding
  • Muscle wasting and loss of topline
  • Regional fat deposits

As PPID progresses, horses can develop additional symptoms, including:

  • Weight loss
  • Abnormal sweating
  • Skeletal atrophy
  • Tendon atrophy
  • Infertility
  • Neurological problems
  • Increased thirst and urination

At advanced stages, horses are more susceptible to infections because of immune suppression. [6] Horses with PPID are more prone to dental, skin, sinus infections, and intestinal parasites.

Insulin Resistance

Horses with PPID are often insulin resistant, which means the cells in their body do not respond normally to the hormone insulin.

Approximately 30% of horses with PPID have high blood insulin levels because their tissues are less sensitive to this hormone.

Insulin regulates the metabolism of sugar (glucose) in the body by signalling tissues to take in glucose from the bloodstream. It also stimulates tissues to utilize glucose to produce glycogen, a form of energy that is stored in the body.

In horses with insulin resistance, the signalling effect of this hormone is impaired and cells cannot take up as much glucose from the blood. As a result, the pancreas continues to produce more insulin, resulting in hyperinsulinemia (high blood insulin levels). [24]

Symptoms of insulin resistance include the accumulation of fatty deposits on the neck, top of the tail, shoulders, and mammary glands. Other signs include excessive urination and thirst.

Chronically high insulin levels are associated with Equine Metabolic Syndrome (EMS) and are often present in PPID. [7]

Horses with PPID should be tested for insulin dysregulation to avoid related health complications.

Increased Risk of Laminitis

Horses with both PPID and insulin dysregulation are at risk of developing laminitis. [8][9]

High levels of insulin (hyperinsulinemia) are implicated in the development of laminitis, although the exact mechanisms are still being researched. Inflammation, vasoconstriction and endothelial damage are three proposed disease pathways.

Insulin dysregulation is diagnosed in horses with elevated levels of this hormone or with abnormal insulin response after eating a meal or an oral sugar test (glucose challenge).

PPID is not on its own a risk factor for laminitis. Horses with PPID that do not have EMS and associated insulin resistance are typically not considered at high risk for laminitis.

Causes of PPID

Researchers do not know exactly what causes the degeneration of dopamine neurons in the hypothalamus.

One theory is that neurons are damaged by free radicals that are produced during metabolic processes. [10] Horses with PPID may be at greater risk of oxidative stress in their hypothalamus. [11]

Oxidative stress (excessive damage by free radicals), is known to alter the chemical structure of cells, proteins, and DNA. Ultimately, it can decrease the number of healthy dopamine-producing neurons that send signals between the hypothalamus and pituitary pars intermedia.

With fewer of these neurons, there is less inhibition of pituitary hormone production by dopamine. Higher levels of pituitary hormones in circulation lead to a broad range of symptoms, together indicating PPID.

How is PPID Diagnosed?

Your veterinarian may diagnose your horse with PPID after evaluating clinical signs and conducting diagnostic testing.

PPID diagnosis can be done at any time, but the interpretation of results will need to take into account seasonal variations in pituitary hormones.

Early intervention is necessary to avoid more advanced health complications due to the disease. If you observe the common symptoms in your senior horse, consult with your veterinarian as soon as possible.

Baseline ACTH Test:

To perform a baseline ACTH test, your veterinarian will collect a blood sample and measure the level of the hormone ACTH in the blood (plasma) compared to a reference range. [12]

A high level of ACTH in the blood can indicate that a horse has PPID. However, ACTH concentrations can vary with stress, illness, exercise, and diet.

Additionally, there is a physiologic (normal) increase in ACTH concentration July through November in North America. This can make test interpretation difficult! If your horse is tested during this season, your veterinarian will need to consider seasonal reference ranges or may recommend additional testing outside of the Fall. [13]

This test detects moderate to advanced cases of PPID, but may not detect mild or early-stage PPID in horses. [14]

Thyrotropin-Releasing Hormone (TRH) Stimulation Test:

TRH stimulation tests are used in combination with the ACTH test to confirm a positive diagnosis of PPID when ACTH testing is inconclusive. [15]

After collecting a blood sample for a baseline ACTH test, TRH is administered intravenously, and a second ACTH sample is collected approximately 10 minutes later. [16]

In horses with PPID, ACTH levels increase after administering TRH. An ACTH concentration higher than 100pg/mL is indicative of PPID. [16]

Dexamethasone Suppression Test:

Previously a popular test for diagnosing PPID, the dexamethasone suppression test is now considered less reliable than other tests.

This test requires administering the corticosteroid dexamethasone to horses intravenously or as an injection into the muscle. Blood samples are collected 24 hours later to measure the level of the hormone cortisol. [16]

In horses with PPID, an injection of dexamethasone increases cortisol in the blood. [17] In healthy horses, dexamethasone suppresses cortisol levels.

Insulin Testing

PPID and Equine Metabolic Syndrome (EMS) occur together in some horses, but not all. It is recommended to test all PPID horses for insulin resistance. [18]

Insulin levels are tested using a combination of a basal insulin test and an oral glucose challenge test.

A basal insulin test involves collecting a blood sample after a horse has fasted for approximately six hours.

Only 30% of horses with EMS have high insulin levels when fasting. The oral glucose challenge is also recommended to identify horses with insulin resistance.

A glucose challenge test involves collecting blood before and after feeding a horse corn syrup to measure how much insulin is released in response to sugar. An analysis is performed on both samples to assess insulin sensitivity.

Treatment of PPID

While there is no cure for PPID, it is very manageable with appropriate treatment. Treatment is aimed at reducing the clinical symptoms of the disease and are required for the lifespan of the affected horse. Many horses go on to have excellent quality of life post-diagnosis.

The prognosis for horses with PPID varies, as does the medication protocol required for a positive response.

Treating the condition earlier may improve the quality of life of affected horses and potentially avoid complications, including infections and laminitis.

Medication

Pergolide mesylate is the only drug licensed for the treatment of PPID in horses and is considered the gold-standard treatment. Originally developed to treat Parkinson’s disease in humans, it is an oral medication administered once per day.

Prascend is the only FDA-approved pergolide formulation for horses. Compounded formulations of pergolide are not recommended due to variations in drug concentration and instability over time.

Pergolide regulates the pituitary gland by acting as a dopamine replacement. It decreases the rel