Equine Cushing’s Disease is a disorder of the endocrine system that affects the pituitary gland and causes metabolic dysfunction. It is commonly called Pituitary Pars Intermedia Dysfunction (PPID). This helps clinically differentiate it from human Cushing’s disease, which affects a different section of the brain. It is most common disease of horses over 15 years old and affects horses across all breeds [1] [2] [3].
The pituitary gland is a structure located at the base of the brain, just below the hypothalamus. Normally, the hypothalamus communicates with the pituitary gland to tell it when to release certain hormones. PPID occurs when neurons controlling the hypothalamus degenerate, causing an important feedback pathway between the hypothalamus and pituitary gland to go unchecked [1]. An enlargement of the middle lobe of the pituitary gland causes an overproduction of hormones that leads to metabolic dysregulation [1] [2] [3] [4]. The enlarged pituitary lobe can also compress other nearby structures (i.e. other pituitary lobes, hypothalamus), which can cause loss of function [1].
Symptoms of Pituitary Pars Intermedia Dysfunction
The most common symptoms of PPID are excessive hair growth (hypertrichosis), excessive thirst (polydipsia), excessive urination (polyuria), lethargy, loss of muscle mass, and laminitis [1] [2] [3] [4]. Horses with PPID have a tendency to develop frequent sinus and skin infections as well as dental diseases [1] [2] [3] [4]. The chronic and debilitating nature of these comorbidities can make daily life and symptom management challenging.
In addition, many horses with PPID develop insulin resistance [1] [2] [3] [4]. Insulin is a hormone that is secreted by the pancreas, and it plays an important role in regulating the levels of glucose in the bloodstream and tissues. With insulin resistance, a horse’s pancreas still continues to make and release normal amounts of insulin in response to elevated blood glucose levels, but its tissues do not respond as readily to the insulin [1] [2] [3] [4] [5] [6]. This results in less glucose entering the tissues that need energy and more glucose building up in the bloodstream. Insulin levels in the bloodstream also become elevated as the body tries to compensate for insulin’s lower effectiveness in the tissues.
Adrenocorticotropic hormone (ACTH) is one of the main hormones affected by PPID. The overproduction of ACTH causes cortisol levels to rise, making the horse’s body react as though it is in a constant state of stress. The most common way to diagnose PPID is by measuring ACTH levels at rest [1] [2] [3] [4].
Treatment Options for Pituitary Pars Intermedia Dysfunction
The treatment of choice and only FDA approved treatment for PPID in horses is pergolide mesylate (sold as tablets under the brand name Prascend®) [1] [2] [3] [4] [7]. Pergolide works primarily by stimulating dopamine receptors, which stops the pituitary gland from overproducing hormones [1]. Other medications have been used alone and in combination with pergolide, but there is little evidence to show they are effective. Pergolide has been shown to be effective at reducing the clinical signs and slowing the progression of PPID [1] [7].
Unfortunately, this medication has many adverse effects such as anorexia, colic, weight loss, and behavioral changes [1] [9].
Pergolide is a prohibited substance under Fédération Équestre Internationale (FEI) and United States Equestrian Federation (USEF) [9]. Horses that have veterinarian documented PPID and have gained the proper Therapeutic Use Exemption (TUE) are allowed to remain on the medication without a withdrawal period prior to competition [10].
In addition to medication, supportive care and therapies are highly important in managing PPID and ensuring good quality of life for affected horses. Preventive medicine, proper vaccinations, regular deworming, and routine dental exams are all critical for horses with PPID.1-4 Regular farrier work is also important, particularly for horses with laminitis [1] [2] [3] [4]. Routine clipping for horses that fail to shed is also helpful, especially in warm weather [1] [2] [3] [4]. Horses with PPID often require analgesics regularly to manage pain and inflammation, especially when they suffer from laminitis. Not all horses with PPID are insulin resistant, but horses that are must be fed a diet that is low in non-structural carbohydrates (NSCs). This keeps blood insulin levels low and prevents too much glucose from building up in the bloodstream.
Another type of supportive care that could potentially benefit horses with PPID is the administration of cannabidiol (CBD). While a study conducted by Turner et al. at University of Kentucky showed that CBD did not significantly influence ACTH levels in senior horses, it did show that CBD reduced levels of cytokine molecules that contribute to inflammation without causing any negative side effects [11]. CBD may not be a direct treatment for PPID, but it can provide symptomatic relief that can greatly improve an affected horse’s quality of life. Its anti-inflammatory, antioxidant, and neuroprotective properties can be greatly beneficial to an aging horse, and its ability to act as a non-steroidal analgesic makes CBD helpful for alleviating pain due to laminitis.
Brave Horse offers a variety of products to help owners easily administer CBD to horses suffering from PPID. CBD oil and Kelso’s Cubes are great options for giving a horse a tasty, precisely measured dose of CBD. However, horses that have also developed insulin resistance, check out Bo’s OatBites. They are made without any added sugar, and each treat contains just one carbohydrate. This allows horses with insulin resistance to benefit from the anti-inflammatory effects and analgesic properties of CBD without consuming excessive sugar or starch.
Final Thoughts
Equine Cushing’s Disease (more accurately called Pituitary Pars Intermedia Dysfunction or PPID), is an endocrine disorder that affects older adult horses across all breeds. It is primarily caused by an overproduction of hormones in the pituitary gland that is attached to the base of the brain. The first sign of PPID is often excessive hair growth (hypertrichosis) and inability to shed properly. Other symptoms are excessive thirst (polydipsia), excessive urination (polyuria), lethargy, loss of muscle mass, laminitis, and greater tendency to develop sinus and skin infections and dental disease. In some cases, horses with PPID also develop insulin resistance. The most common way to diagnose PPID is by laboratory measurement of adrenocorticotropic hormone (ACTH) in blood serum. The only FDA-approved treatment for PPID is pergolide mesylate; it reduces clinical signs and slows disease progression but causes adverse effects such as anorexia, colic, weight loss, and behavioral changes. Because the disease cannot be cured, supportive care is highly important for ensuring good quality of life. Preventive medicine, vaccinations, deworming, and routine dental exams as well as regular farrier work and body clipping are all important for ensuring health and well-being. Additionally, horses with insulin resistance must adhere to a low non-structural carbohydrate (NSC) diet. Many horses also require non-steroidal anti-inflammatory drugs (NSAIDs) to assist with pain management. Use of cannabidiol (CBD) may be a useful supportive therapy for horses with PPID because of its anti-inflammatory, antioxidant, and analgesic effects.
References
[1] Kirkwood, N. C.; Hughes, K. J.; Stewart, A. J. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Veterinary Sciences 2022, 9 (10), 556. https://doi.org/10.3390/vetsci9100556.
[2] Equine Cushings Disease: Equine Pituitary Pars Intermedia Dysfunction | AAEP. aaep.org. https://aaep.org/issue/equine-cushings-disease-equine-pituitary-pars-intermedia-dysfunction.
[3] Equine Endocrinology: Pituitary Pars Intermedia Dysfunction (PPID). The College of Veterinary Medicine at Michigan State University. https://cvm.msu.edu/vdl/client-education/guides-for-pet-owners/equine-endocrinology-pituitary-pars-intermedia-dysfunction-ppid#:~:text=What%20is%20PPID%3F.
[4] Young, A. Pituitary Pars Intermedia Dysfunction | School of Veterinary Medicine. ceh.vetmed.ucdavis.edu. https://ceh.vetmed.ucdavis.edu/health-topics/pituitary-pars-intermedia-dysfunction-ppid#:~:text=The%20most%20common%20clinical%20signs
[5] Insulin resistance. College of Veterinary Medicine. https://vetmed.umn.edu/equine/research/equine-genetics-and-genomics-laboratory/projects/equine-metabolic-syndrome/insulin-resistance#:~:text=Insulin%20resistance%20occurs%20when%20insulin
[6] Equine Metabolic Syndrome – Metabolic Disorders. Merck Veterinary Manual. https://www.merckvetmanual.com/metabolic-disorders/equine-metabolic-syndrome/equine-metabolic-syndrome?query=ppid&_gl=1
[7] Pergolide study. College of Veterinary Medicine. https://vetmed.umn.edu/equine/research/equine-genetics-and-genomics-laboratory/projects/equine-pituitary-pars-intermedia-dysfunction-ppid/pergolide-study#:~:text=The%20only%20FDA%20approved%20drug
[8] Prascend® (pergolide tablets) Prescribing Information. https://prascend.com/sites/default/files/2023-04/prascend-marketing-prescribing-information.pdf
[9] 2024 Equine Prohibited Substances List. https://inside.fei.org/sites/default/files/2024%20Prohibited%20Substances%20List.pdf
[10] US Equestrian. US Equestrian. https://www.usef.org/faqs/therapeutic-use-exemption-tue-status-for
[11] Turner, S.; Knych, H. K.; Adams, A. A. The Effects of Cannabidiol on Immune Function and Health Parameters in Senior Horses. Veterinary Immunology and Immunopathology 2023, 257, 110549. https://doi.org/10.1016/j.vetimm.2023.110549.
