Pituitary pars intermedia dysfunction (PPID), historically called equine Cushing’s disease, is the most common endocrine disorder of aging horses and ponies. The disease is progressive, neurodegenerative and closely associated with metabolic dysfunction, immune suppression, muscle wasting and laminitis. Modern research has substantially changed how veterinarians understand PPID, particularly its neurologic origins and relationship with insulin dysregulation. Estimates suggest that approximately 20%-25% of horses over 15 years of age may be affected, although many cases remain underdiagnosed during the early stages of disease. 

What Is PPID?

PPID is a neurodegenerative disorder involving the hypothalamic dopaminergic neurons that regulate the pars intermedia region of the pituitary gland. In healthy horses, dopamine inhibits hormone production from the pars intermedia. In horses with PPID, degeneration of these neurons reduces dopamine signaling, resulting in hyperplasia or adenoma (benign tumor) formation within the pars intermedia and excessive secretion of proopiomelanocortin (POMC)-derived peptides, including adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), β-endorphin and corticotropin-like intermediate peptide (CLIP). Cortisol concentrations in horses with Cushing’s are often inconsistent or normal. As a result, PPID is not simply viewed as a disorder that increases cortisol (hypercortisolemic); it is now recognized as a dopaminergic neurodegenerative disease. 

The most common risk factor for developing Cushing’s is age, and it affects approximately 20%-25% of horses over the age of 15 years old. Younger horses may occasionally develop disease. Ponies also appear to be overrepresented in some populations, potentially due to longevity and concurrent metabolic predisposition. PPID often develops gradually over several years and early clinical signs may be subtle or easily mistaken for normal aging. Signs that your horse may have Cushing’s are:

An explanation of how pituitary pars intermedia dysfunction (PPID or equine Cushing’s disease) works. AI graphic created by Neely Heidorn

Diagnosis of Cushing’s disease is based on a combination of clinical signs and endocrine testing rather than a single finding. Veterinarians typically begin by evaluating the characteristic features previously listed, then confirming suspicion with laboratory testing — most commonly with the measurement of basal plasma adrenocorticotropic hormone (ACTH) concentration, interpreted with appropriate seasonal reference ranges. In horses with early or equivocal disease, a thyrotropin-releasing hormone (TRH) stimulation test may be used to improve diagnostic sensitivity.

Once diagnosed, treatment focuses on restoring dopaminergic inhibition and managing systemic effects. The gold-standard therapy is pergolide mesylate, a dopamine agonist that reduces POMC-derived hormone production and improves clinical signs, often within weeks to months. Long-term management is equally important and includes a low nonstructural carbohydrate diet, careful pasture control, routine monitoring of ACTH concentrations and proactive management of complications such as laminitis, infections, and dental or hoof issues. Because PPID is progressive, horses require lifelong treatment and periodic dose adjustments to maintain control of the disease.

If you feel like your horse is developing any of the symptoms listed above, it is important to discuss them with your veterinarian and develop an individualized management plan.

An aged horse showing signs of pituitary pars intermedia dysfunction. Photo by Kim Pope Brown

References

Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Veterinary Sciences. 2022;9(10):556.

Ireland J, McGowan CM. Epidemiology of pituitary pars intermedia dysfunction: A systematic literature review of clinical presentation, disease prevalence and risk factors. Veterinary Journal. 2018;235:22–33.

Menzies-Gow NJ. Equine Pituitary Pars Intermedia Dysfunction. Veterinary Sciences. 2025;12(8):780.

Tatum RC, McGowan CM, Ireland JL. Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review. Veterinary Journal. 2020;266:105562.

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09/28/26
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