Equine Cushing's Disease (Pituitary Pars Intermedia Dysfunction)

TL;DR. Equine Cushing's Disease (PPID) is a progressive endocrine disorder in horses caused by the degeneration of dopamine-producing neurons, leading to hormonal imbalances that cause long hair coats and high blood sugar.

A long, curly hair coat that fails to shed in the spring is one of the most common signs of Equine Cushing's Disease.

What is it?

Equine Cushing's Disease, scientifically known as Pituitary Pars Intermedia Dysfunction (PPID), is a common degenerative endocrine disease of horses. Unlike Cushing's disease in dogs or humans, which typically involves the middle or outer layers of the adrenal glands, the equine version specifically involves a section of the pituitary gland located at the base of the horse's brain: the pars intermedia (the intermediate lobe).

In a healthy horse, the brain regulates the pituitary gland using a chemical messenger called dopamine. Dopamine is produced by neurons in the hypothalamus and acts as a natural brake, keeping the activity of the pars intermedia in check. In horses with PPID, these dopamine-producing neurons slowly degenerate over time. Without the inhibitory influence of dopamine, the cells of the pars intermedia multiply and grow larger, leading to an overproduction of hormones. Specifically, this overactive tissue leads to an increased expression of proopiomelanocortin (POMC) peptides, which are precursor proteins that break down into several active hormones, including adrenocorticotropic hormone (ACTH).

This flood of hormones disrupts the horse's entire endocrine system, affecting metabolism, immune function, and muscle maintenance. Because the disease is progressive and degenerative, understanding its mechanisms helps horse owners appreciate why daily, lifelong treatment is necessary to maintain their horse's quality of life.

PPID originates in the pars intermedia of the pituitary gland due to a lack of dopamine from the hypothalamus.

Causes & risk factors

The primary cause of PPID is the age-related degeneration of dopaminergic neurons in the hypothalamus. The exact reason why these specific neurons degenerate in some horses and not others remains a subject of ongoing veterinary research, though oxidative stress associated with aging is believed to play a significant role.

Our structured clinical records indicate that there are no specific breed predispositions for Equine Cushing's Disease. Any breed of horse, pony, miniature horse, or donkey can develop the condition. However, it is overwhelmingly a disease of senior animals. It is rarely diagnosed in horses under the age of 10, and the risk increases significantly as horses pass their 15th year.

Signs to watch for

The clinical signs of PPID can develop so gradually that owners often mistake early symptoms for normal signs of aging. However, as the hormonal imbalances progress, several distinct symptoms emerge:

• Hair coat changes (Common): This is the classic hallmark of PPID. Horses may fail to shed their winter coats in the spring, shed late, or grow an abnormally long, thick, and sometimes curly coat (a condition known as hirsutism or hypertrichosis). This occurs because the elevated hormones disrupt the natural hair follicle growth cycles.
• Hyperglycemia (Common): Elevated blood sugar levels occur because the hormonal imbalance interferes with insulin regulation, leading to insulin resistance. Over time, this can lead to secondary complications like laminitis.
• Muscle wasting (Common): Loss of muscle mass, particularly along the topline and rump, is common. This can give the horse a swaybacked appearance and a pot-bellied abdomen.
• Lethargy and decreased performance (Common): Affected horses often seem sluggish, have a decreased tolerance for exercise, and may appear depressed.
• Abnormal fat deposition (Common): Horses may develop unusual fat pads, particularly above the eyes (supraorbital fat), along the crest of the neck, or around the tailhead, even if they are losing weight elsewhere.
• Increased drinking and urination (Common): Also known as polydipsia and polyuria, this is driven by the metabolic changes and elevated blood glucose levels.
• Chronic infections (Common): The hormonal elevations suppress the immune system, making these horses highly susceptible to recurrent infections, such as skin infections, tooth root abscesses, and pastern dermatitis.

Untreated PPID and associated hyperglycemia can lead to painful, chronic laminitis in the hooves.

How vets diagnose it

Diagnosing PPID requires a combination of a thorough physical examination, a review of the horse's history, and specific endocrine blood tests. Because early signs can be subtle, diagnostic testing is highly recommended for any senior horse showing changes in coat, body condition, or energy levels.

Your veterinarian will typically perform a baseline blood test to measure endogenous ACTH levels. Because ACTH levels naturally fluctuate throughout the year—rising significantly in the autumn—vets must interpret these results using seasonally adjusted reference ranges.

For cases that are difficult to diagnose or when baseline tests are inconclusive, your vet may recommend an ACTH stimulation test. This test evaluates how the horse's endocrine system responds to a stimulating hormone, helping to confirm the diagnosis. As noted in a leading veterinary drug reference:

"HORSES: ACTH Stimulation Test:
a) Draw baseline blood sample for cortisol determination an..." [4]

By measuring the hormonal response before and after stimulation, your veterinarian can accurately assess the function of the pituitary-adrenal axis and establish a definitive diagnosis.

Treatment options

While there is no cure for PPID, the disease can be highly managed with daily medication and supportive care. Treatment focuses on restoring the chemical balance in the brain to reduce hormone production.

First-Line Therapy: Dopamine Agonists

The primary medical treatment for PPID is Pergolide, a dopamine agonist. Pergolide works by mimicking the action of dopamine, binding to receptors on the overactive cells of the pars intermedia. This effectively reinstates the "brake" on the pituitary gland, reducing the secretion of POMC peptides and normalizing hormone levels.

Pergolide therapy is lifelong and requires careful monitoring. The dosage must be tailored to the individual horse based on clinical response and follow-up blood tests. As detailed in a leading veterinary internal medicine reference:

"If no improvement is noted within 8-12 weeks (depending on season as hair coat changes will vary with the time of year that treatment is initiated), the daily dose can be increased by 0. 002 mg/kg monthly up to a total dose of 0. 006 mg/kg (3 mg/day for a 500 kg horse). If only a limited response is observed with 0. 006 mg/kg dose and endocrinologic test results remain abnormal, the author typically" [3]

Your veterinarian will schedule regular blood tests (usually every 6 to 12 months) to ensure the dosage remains effective, especially during the autumn when pituitary activity naturally spikes.

Second-Line Therapy: Antihistamines / Serotonin Antagonists

For horses that do not fully respond to Pergolide alone, veterinarians may introduce Cyproheptadine as an adjunctive treatment. Cyproheptadine is an antihistamine and serotonin antagonist. Because serotonin is another neurotransmitter that stimulates the release of pituitary hormones, blocking its action can help further suppress the overactive pars intermedia when used in combination with a dopamine agonist.

Supportive Care and Management

In addition to medication, daily husbandry is critical for managing PPID:

• Dietary Management: Because hyperglycemia and insulin resistance are common, horses with PPID should be fed a diet low in non-structural carbohydrates (NSCs) to prevent dangerous spikes in blood sugar.
• Clipping: Horses that fail to shed their thick coats should be body-clipped in the spring and summer to help them regulate their body temperature and prevent skin infections like pastern dermatitis.
• Regular Farriery: Due to the high risk of laminitis, strict attention to hoof care is vital.

Prognosis

Specific long-term prognosis data and survival statistics for PPID are limited in our structured clinical records. However, standard veterinary experience shows that while PPID is a progressive, degenerative disease, the prognosis for a good quality of life is excellent with early diagnosis and consistent management.

Many horses diagnosed with PPID live comfortable, active, and useful lives for many years after diagnosis. The key to a favorable outcome is strict adherence to the daily medication regimen, routine veterinary monitoring, and proactive management of secondary complications like laminitis and infections.

Prevention

Because PPID is a degenerative disease associated with the natural aging process, there is no known way to prevent its onset. It is not caused by poor management or diet.

However, you can prevent the severe complications of the disease through early detection. Including endocrine screening (such as baseline ACTH testing) in the annual wellness exams of any horse over the age of 15 allows you to start treatment before irreversible damage, such as severe laminitis or profound muscle wasting, occurs.

When to call your vet

If your horse has been diagnosed with PPID or is showing early signs, you should monitor them closely. Contact your veterinarian immediately if you observe any of the following red flags:

• Signs of laminitis: Shifting weight, a hesitant or "ouchy" gait, heat in the hooves, an increased digital pulse, or a rocked-back stance. Laminitis is a medical emergency.
• Signs of infection: Non-healing wounds, swelling, discharge, or crusting skin lesions (such as pastern dermatitis).
• Extreme lethargy or depression: A sudden drop in energy or refusal to eat.
• Suspected medication overdose: If your horse accidentally accesses their medication, contact your vet right away. While horses generally tolerate Pergolide well, monitoring is essential. As noted in veterinary toxicology records regarding accidental exposures:

"In these cases 8 were dogs with all 8 showing clinical signs, and the remaining 1 case was a horse showing no clinical signs. Common findings in dogs recorded in decreasing frequency included vomiting, lethargy, hypertension, and ptosis. Treatment is supportive." [2]

Even if your horse initially shows no clinical signs after an accidental double-dose or overdose, professional veterinary guidance is necessary to ensure their safety.

Sources

• Plumb's Veterinary Drug Handbook, page 909, 2819, 2823, 2824.