Case reports suggest oral cabergoline may offer alternative treatment for challenging equine PPID cases

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  The Equine Cushing's and Insulin Resistance Group Inc. (ECIR Group) has announced the publication of a new retrospective case report by Eleanor M. Kellon, VMD, examining the use of oral cabergoline as a treatment option for horses with equine pituitary pars intermedia dysfunction (PPID) that failed to respond to conventional therapy. 

PPID, commonly known as equine Cushing's disease, is most often managed with oral pergolide, which has become the standard treatment due to its high success rate in controlling clinical signs and hormone levels. However, a subset of horses either fails to respond adequately to pergolide or develops unacceptable behavioural or gastrointestinal side effects, leaving veterinarians and owners with limited therapeutic alternatives.

Until now, the primary alternative has been injectable sustained-release cabergoline. There is little published information on other oral treatment options.

Dr. Kellon's report, published in the Open Veterinary Journal, reviews the outcomes of five horses owned by ECIR Group members that were treated with daily oral cabergoline under the supervision of their attending veterinarians 

"All horses were confirmed PPID by Cornell University Vet Diagnostic Laboratory criteria, and were considered failures of mainline therapy due to inability to control ACTH and clinical signs," Dr. Kellon said. "Based on the success in a 2022 study*, members of the ECIR Group, under the direct care of their personal veterinarians, decided to try oral cabergoline as an alternative to pergolide or injectable cabergoline." 

The horses represented particularly challenging cases. All had previously failed to respond adequately to treatment with oral pergolide. Four of the five had also been treated with injectable sustained-release cabergoline, but this had been unsuccessful because of severe injection-site reactions, gastrointestinal side effects, or both. All of the horses had either longstanding PPID or rapidly progressive disease.

Despite the severity of these cases, the retrospective review found encouraging responses following the introduction of oral cabergoline. No changes were made to diet, concurrent medications, or overall management, allowing the observed improvements to be attributed to the change in therapy.

Although limited to a small number of horses, the findings suggest that daily oral cabergoline may provide a well-tolerated and effective alternative for PPID patients that cannot be successfully managed with pergolide or injectable cabergoline.

Dr. Kellon emphasised that these preliminary observations warrant further investigation. She believes additional research is needed to better understand the pharmacodynamics and pharmacokinetics of oral cabergoline in horses, establish its side-effect profile, and determine effective dosing strategies, particularly in horses with less severe disease.

While larger prospective studies will be necessary to confirm these findings, the report provides early evidence that oral cabergoline could expand treatment options for veterinarians managing some of the most difficult cases of equine PPID.

 

For more details, see:

Eleanor M. Kellon. 

Oral cabergoline for the management of equine pituitary pars intermedia dysfunction: Five cases.

Open Vet. J.. 2026; 16(6): 3818-3825.

https://doi.org/10.5455/OVJ.2026.v16.i6.52

 

*Godoy, A.F. and De La Fuentes, C.I. 

Cabergoline monotherapy in a Chilean creole horse with pituitary pars intermedia dysfunction (Cushing’s disease): a case report. 

Clin. Res. AnimSci. (2022) 2(3), 1–4

 

Pituitary Pars Intermedia Dysfunction (PPID) and the potential role of β-endorphin in diagnosis

Pituitary Pars Intermedia Dysfunction (PPID), commonly known as equine Cushing’s disease, is a common endocrine disorder affecting older horses. The condition is associated with abnormal activity of specialised cells called melanotropes, which are located in the pars intermedia region of the pituitary gland. These cells normally produce several hormones derived from a precursor molecule known as pro-opiomelanocortin (POMC). In horses affected by PPID, melanotropes become overactive, leading to excessive production of several hormones that contribute to the clinical signs observed in the disease.

One of the most important hormones produced by melanotropes is adrenocorticotrophic hormone (ACTH). This hormone stimulates cortisol release from the adrenal glands and is widely used as a diagnostic marker for PPID. Elevated ACTH concentrations in blood samples often support a diagnosis of the disease. However, ACTH may not provide a complete understanding of PPID, as melanotropes also produce other biologically active substances that may influence disease development and clinical signs.

These additional substances include alpha-melanocyte stimulating hormone (α-MSH), corticotropin-like intermediate peptide (CLIP), and β-endorphin. β-endorphin is a peptide hormone composed of 31 amino acids and functions as part of the body’s natural pain and stress regulation system. The amino acid sequence of equine β-endorphin is very similar to that found in humans, differing by only three amino acids. Because β-endorphin is also derived from POMC and secreted by melanotropes, researchers have suggested it may play an important role in the development and progression of PPID.

Traditionally, β-endorphin concentrations in horses have been measured using radioimmunoassay (RIA). However, this technique involves the use of radioactive materials, which presents safety risks and has become less widely available in recent years. In human medicine, enzyme-linked immunosorbent assays (ELISAs) are commonly used as a safer and more accessible alternative for hormone measurement. Researchers have therefore investigated whether commercially available human β-endorphin ELISA tests could be used reliably for equine samples.

A study conducted by Nathalie Fouché and colleagues at the University of Bern, Switzerland, aimed to validate a human β-endorphin ELISA kit for use in horses and to compare β-endorphin concentrations between horses diagnosed with PPID and healthy control horses. Validation of the test involved comparing standard curves generated using both synthetic equine β-endorphin and human β-endorphin. The results demonstrated full parallelism between the curves, indicating the test could accurately measure equine hormone levels.

The researchers also assessed the reliability of the assay by calculating intra-assay and inter-assay variation. These tests measure consistency within a single test plate and between multiple plates. The assay showed acceptable levels of variation, suggesting it is suitable for research use. Additionally, β-endorphin concentrations remained stable in plasma samples over a 24-hour period regardless of centrifugation timing, storage temperature, or storage duration, which supports the practicality of sample handling.

The pilot study compared five horses diagnosed with PPID to twenty healthy aged control horses. The findings revealed significantly higher β-endorphin concentrations in horses with PPID, with median concentrations of 506 pg/mL compared to 35 pg/mL in healthy horses. These results suggest that β-endorphin may be elevated in horses with PPID and could potentially provide additional diagnostic or pathophysiological information alongside ACTH testing.

Overall, this research highlights the possible importance of β-endorphin in understanding PPID and suggests that ELISA-based testing may provide a safer and more accessible method for future investigation. Further studies with larger sample sizes are required to confirm the diagnostic value of β-endorphin in horses with PPID.

For more details, see: 

N. Fouché, J. Howard, V. Gerber, P. Billmann, M. Farinha do Sul, G. Christen, R. Bruckmaier, C. Philipona, N. Besuchet Schmutz, J. Gross,

Pilot study of β-endorphin concentrations in horses with pituitary pars intermedia dysfunction using a newly validated enzyme-linked immunosorbent assay,

Domestic Animal Endocrinology (2026) vol 95,106982

https://doi.org/10.1016/j.domaniend.2025.106982

Seasonal and breed differences in resting ACTH

Pituitary pars intermedia dysfunction (PPID), commonly referred to as equine Cushing’s
disease, is a common endocrine disorder primarily affecting older equids. Current estimates suggest that approximately 25% of horses and ponies aged 15 years and older may be affected.

The condition arises from degeneration of dopaminergic neurons within the hypothalamus, leading to loss of regulatory control over the pars intermedia region of the pituitary gland. As a result, excessive production of several hormones, including adrenocorticotropic hormone (ACTH), occurs. Although PPID is progressive and currently incurable, early diagnosis and appropriate management can significantly slow disease progression and improve equine welfare.

Clinical signs of PPID are variable and may develop gradually. Common indicators include hypertrichosis (abnormal or excessive hair growth), delayed or incomplete shedding of the winter coat, lethargy, weight loss, and metabolic disturbances. One of the most serious associated complications is laminitis, which can severely compromise quality of life and may become life-threatening. Due to the variable presentation of clinical signs, diagnostic testing is frequently required to support clinical suspicion.

Measurement of baseline plasma ACTH concentration is widely used as a primary diagnostic tool for PPID. However, interpretation of ACTH values is complex, as concentrations are influenced by several factors, particularly seasonal variation. In the Northern Hemisphere, resting ACTH levels typically rise during late summer and early autumn, approximately between August and October. Understanding these physiological fluctuations is essential to avoid misinterpretation of results and potential overdiagnosis.

Breed-related differences in ACTH concentrations have also been documented. An Australian study identified that pony breeds, particularly Shetland ponies, displayed significantly higher ACTH concentrations during autumn when compared with Thoroughbred horses. These findings suggest that species, breed type, and possibly body size may influence endocrine responses and should be considered during diagnostic evaluation.

Further research has expanded understanding of ACTH variation across different equid species. A study conducted by Goodrich and colleagues, involving researchers from Cornell University, the University of California, Davis, and private veterinary practice, investigated baseline ACTH concentrations in donkeys and horse–donkey hybrids across several regions of the United States. The study aimed to provide a more comprehensive understanding of seasonal ACTH variation in healthy equids, as previous research had been limited by small sample sizes and restricted geographic representation.

The study evaluated 19 standard donkeys, 14 miniature donkeys, and 28 hybrids, with animals located in California, Massachusetts, New York, and Texas. Blood samples were collected twice monthly from June to November 2019 and monthly from December 2019 to May 2020. Results demonstrated a clear seasonal rise in ACTH concentrations across all groups, with levels increasing from mid-August and peaking in late September. Mean ACTH concentrations during peak periods reached approximately 109.6 pg/mL in standard donkeys, 134.6 pg/mL in miniature donkeys, and 100.8 pg/mL in hybrids.

Notably, hybrids consistently exhibited lower ACTH concentrations compared to donkeys throughout the year. During the seasonal peak, ACTH levels in hybrids were 23% lower than in standard donkeys and 51% lower than in miniature donkeys. Similar differences persisted during non-peak periods, with hybrids showing reductions of approximately 30% compared to both donkey groups. These findings highlight important species-related differences that may influence diagnostic interpretation.

Overall, research demonstrates that accurate diagnosis of PPID requires careful consideration of seasonal variation, species differences, and breed predisposition alongside clinical assessment. Improved understanding of normal ACTH fluctuations in healthy equids enhances diagnostic accuracy and supports more effective management of this common and welfare-significant endocrine disorder.

 

For more details, see:

Goodrich, Erin L., Sebastián Gonzalo Llanos-Soto, Renata Ivanek, Toby Pinn-Woodcock, Elisha Frye, Amy Wells, Stephen R. Purdy, Emily Berryhill, and Ned J. Place.

Both Season and Equid Type Affect Endogenous Adrenocorticotropic Hormone Concentrations in Healthy Donkeys, Mules and Hinnies in the United States

 Animals (2026) 16, no. 2: 290.

https://doi.org/10.3390/ani160202902

Researchers seek horses for PPID treatment response study

  A research team from the University of Minnesota is urgently seeking horse owners and veterinarians to participate in a study on pituitary pars intermedia dysfunction (PPID), more commonly known as equine Cushing’s disease.

PPID affects up to 30% of older horses, causing a range of problems, from poor performance to severe illness and even death. The disease occurs when neurons in the hypothalamus are damaged, disrupting the brain’s ability to regulate the pars intermedia region of the pituitary gland. While there is no cure, treatment focuses on managing symptoms and slowing progression.

The most widely used treatment is pergolide which helps compensate for the dopamine loss seen in affected horses. Originally developed for Parkinson’s disease in humans, pergolide remains the only FDA-approved drug for PPID in horses.

However, horses vary widely in how they respond to this medication. Studies show that 60 - 80% of horses respond well, but definitions of “success” differ. Moreover, adverse effects are common. Anorexia is reported in up to 32% of treated horses, alongside issues like colic, weight loss, and behavioural changes. These side effects often lead owners or veterinarians to reduce or stop treatment, allowing the disease to worsen.

In human medicine, it is well established that genetic differences can influence how individuals respond to drugs. Researchers now believe the same may be true for horses.

To explore this, Dr. Molly McCue and Dr. Lauren Hughes of the UMN Equine Genetics and Genomics Laboratory, together with Dr. Dianne McFarlane at the University of Florida, are leading a study to identify genetic factors that influence pergolide response and side-effect risk in horses with PPID.

“Our goal is to identify genetic variants that influence treatment outcomes,” explain the researchers. “If we can find alleles that predict poor response or higher risk of adverse effects, we could tailor dosing and treatment to each horse, making therapy safer and more effective.”

Dr. Hughes adds, “As a veterinarian, I’ve seen how devastating PPID can be for horses and their owners. This research could help us greatly improve diagnosis, treatment, and management of this disease.”

The team is seeking horses diagnosed with PPID by a veterinarian - confirmed through bloodwork - who have been on pergolide therapy for at least six months. They are particularly interested in horses that:

·       Require higher or more frequent doses of pergolide

·       Experience adverse effects such as appetite loss, weight loss, colic, or behavioural changes

Eligible horses should:

·       Be 15 years or older at the time of diagnosis

·       Have clinical signs consistent with PPID (e.g. long, shaggy coat, muscle loss, dullness, or recurrent infections)

·       Have had follow-up blood tests (ACTH, TRH stimulation, or dexamethasone suppression tests)

Participation involves submitting medical records and providing hair root or blood samples. Owners may enrol as many horses as they wish.

The researchers emphasise that participation is vital: by contributing samples and data, owners will help uncover the genetic clues that could shape the future of personalised PPID treatment - offering hope for safer and more effective therapies for horses everywhere.

For more details, see: 

https://vetmed.umn.edu/equine/research/equine-genetics-and-genomics-laboratory/projects/equine-pituitary-pars-intermedia-dysfunction-ppid/pergolide-study

 

https://www.youtube.com/watch?v=kZl2WvUBt1w

University of Minnesota Study Investigates Genetic Influence on PPID Treatment Response in Horses

A research team at the University of Minnesota is investigating the role genetics may play in how
horses respond to treatment for pituitary pars intermedia dysfunction (PPID), commonly known as equine Cushing’s disease. This condition, which affects up to 30% of older horses, can have serious consequences ranging from diminished performance to death.

 

PPID develops when neurons in the hypothalamus become damaged, resulting in the loss of control over the pituitary gland’s pars intermedia. While there is currently no cure, treatment focuses on slowing disease progression and managing clinical signs. The gold-standard medication for PPID is pergolide, a dopamine receptor agonist originally used to treat Parkinson’s disease in humans. Pergolide helps compensate for dopamine loss in hypothalamic neurons and is the most widely prescribed drug for PPID.

 

However, horses vary significantly in their response to pergolide. Treatment success rates are reported to range from 60–80%, but comparisons across studies are difficult due to differing definitions of “success.” Additionally, adverse effects are relatively common, with some studies reporting anorexia in up to 32% of treated horses. Other side effects may include colic, weight loss, and behavioural changes. These reactions often lead owners or veterinarians to reduce or discontinue treatment - causing symptoms to return or worsen and allowing the disease to progress.

 

It is well established in human medicine that genetic differences can influence how individuals respond to medications. Now, the same principle is being explored in horses.

 

The study, led by Dr. Molly McCue and Dr. Lauren Hughes from the UMN Equine Genetics and Genomics Laboratory, in collaboration with Dr. Dianne McFarlane from the University of Florida, aims to uncover genetic factors that affect pergolide response and adverse event susceptibility in horses with PPID.

 

“Our goal is to identify genetic variants that influence treatment outcomes,” explain the researchers. “If we find specific alleles that predict poor response or higher risk of side effects, this could lead to more personalised treatment—such as adjusted dosing strategies to improve safety and effectiveness.”

 

“As a veterinarian, I understand just how devastating PPID can be for horses and the owners that love them,” said Dr. Hughes in a UMN College of Veterinary Medicine news release. “I’m very excited about the potential of this research to improve how we diagnose, treat, and manage this important disease.”

 

The research team is actively seeking suitable horses to enrol in the study. They are looking for horses that meet the following criteria:

• Over the age of 15 at time of PPID diagnosis
• Diagnosis made by veterinarian and diagnosis included bloodwork
• Horse has/had clinical signs consistent with PPID (long shaggy haircoat, muscle atrophy, changes in mentation, or recurrent infections)
• Horse has been on pergolide therapy for a minimum of 6 months and has had recheck blood values (including ACTH, TRH stim, or dexamethasone suppression blood work)

 

If your horse meets the criteria, you are encouraged to participate. Your involvement is essential - this research would not be possible without the support of dedicated horse owners and their animals.

 

For more details, see:

 

https://vetmed.umn.edu/equine/research/equine-genetics-and-genomics-laboratory/projects/equine-pituitary-pars-intermedia-dysfunction-ppid/pergolide-study/pergolide-study-participation-requirements

 

https://www.youtube.com/watch?v=kZl2WvUBt1w

Do endocrine disorders affect anthelmintic performance?

Recent research indicates that insulin dysregulation may affect the performance of anthelmintics
like ivermectin. This suggests that horses with such endocrine disorders might be more prone to parasitic infections.

In a study conducted by Martin Nielsen and colleagues at the University of Kentucky, the response to ivermectin was evaluated in horses with insulin dysregulation (ID), pituitary pars intermedia dysfunction (PPID), or neither condition. 

 

The study population was part of a special herd at the University of Kentucky’s Department of Veterinary Science, which included horses with and without these endocrine disorders. These horses were kept in permanent paddocks without pasture rotation or enhanced hygiene practices and received routine anthelmintic treatments: ivermectin in March or April and July or August, and moxidectin/praziquantel in November.

 

The study focused on senior horses (aged 13 years and over) and those with or without PPID, ID, or both. Out of 47 horses in the research herd, 19 met the criteria for inclusion. These horses, all with positive faecal worm egg counts, were treated with ivermectin at the recommended dose of 200 mcg/kg. Faecal samples were collected before treatment, two weeks post-treatment (for the Faecal Egg Count Reduction Test, or FECRT), and then weekly until worm eggs reappeared in the faeces (Egg Reappearance Period, or ERP).

 

Two laboratory tests were employed to assess the response to ivermectin: the Faecal Egg Count Reduction Test (FECRT) and the Egg Reappearance Period (ERP). For the FECRT, a reduction of at least 99.7% in worm egg counts is considered effective two weeks post-treatment. The ERP for ivermectin is typically 8-10 weeks.

 

The study found no significant differences in the effectiveness of ivermectin between the groups. However, the small sample size may have made it difficult to detect any potential differences. Overall, ivermectin was highly effective, with all horses showing a greater than 99.7% reduction in worm egg counts at the two-week mark. 

 

Nonetheless, the researchers observed that the ERP was shorter in horses with ID and those with both PPID and ID, at six and seven weeks respectively, compared to eight weeks for both the PPID-only and healthy control groups.

 

They suggest that their findings indicate a need for further investigation of the possible influence of endocrine disorders on anthelmintic performance in horses.

 

 

For more details, see:

 

M.K. Nielsen, C.A. Finnerty, N.E. Ripley, A.E. Page, M.E. McClendon, A.A. Adams,

Ivermectin performance in horses diagnosed with equine endocrine disorders,

Veterinary Parasitology, (2024) Vol 328,110182,

https://doi.org/10.1016/j.vetpar.2024.110182

Investigating cabergoline for treating equine Cushing’s disease

 Cabergoline shows promise as a treatment option for equine Cushing’s disease, according to a recent report.

Cushing’s disease or Pituitary Pars Intermedia Dysfunction (PPID) is a common condition in older horses, resulting from increased activity in the intermediate lobe of the pituitary gland. This excessive activity has been attributed to nerve damage impairing its regulation, with dopamine acting as the crucial neurotransmitter. When dopamine levels are deficient, the pituitary gland becomes overactive, leading to the release of various hormones, such as adrenocorticotropic hormone (ACTH).

 

Clinical manifestations associated with PPID are well-documented and include hypertrichosis, laminitis, polyuria, polydipsia, lethargy, muscle wastage, and delayed wound healing.

 

Dopaminergic agonists, medications that mimic the action of dopamine, function by stimulating dopamine receptors in the pituitary gland. This stimulation results in the inhibition of the release of certain hormones, including ACTH, thereby mitigating clinical signs such as abnormal hair coat, muscle wasting, and laminitis.

 

Pergolide, a dopamine agonist, stands as the primary treatment for managing PPID and is approved for oral administration in equines. However, some horses may exhibit resistance to daily oral dosing. Cabergoline, another dopamine agonist like pergolide, currently is not licenced for use in horses.

 

A recent retrospective study conducted by Tania Sundra of Avon Ridge Equine Veterinary Services in Brigadoon, WA, Australia, along with colleagues, explored the efficacy of intramuscular extended-release cabergoline (ERC) injection in treating PPID. Despite being unlicensed, this treatment modality is increasingly utilized off-label in clinical practice for managing PPID. The study examined clinical records of privately-owned horses with PPID that had undergone intramuscular cabergoline treatment at Avon Ridge Equine Clinic.

 

The study examined the short-term (5–8 days) and longer-term (12 months) clinical and endocrinological responses to two doses of cabergoline: a low dose (0.005mg/kg) extended-release cabergoline (LDERC) and a high dose (0.01mg/kg) extended-release cabergoline (HDERC).

 

Results showed that although both doses of ERC led to a decrease in median ACTH concentration, the levels remained above the seasonal reference range in about half of the treated horses. However, similar responses had been noted in previous studies involving pergolide treatment for PPID.

 

Owners reported clinical improvement in 78.3% and 100% of horses treated with LDERC and HDERC, respectively. 

Common side effects of dopamine agonists, such as decreased appetite, lethargy, gastrointestinal upset, and behavioural changes, were observed. Notably, partial, self-limiting inappetence was reported in 30.0% of LDERC cases and 60% of HDERC cases, with seven horses exhibiting lethargy.

 

In cases of partial anorexia, owners noted that horses preferred long-stem forage (hay or grass) over cereal-based feeds. The clinical and endocrinological responses observed were consistent with previous reports of oral pergolide treatment.

 

The authors suggest that weekly injection of ERC may serve as an effective alternative to pergolide. The 0.005 mg/kg dose appeared to be as effective as the 0.01 mg/kg dose but with a lower risk of inappetence.

 

While cabergoline shows promise as a treatment option for PPID in horses, further research is necessary to fully establish its efficacy, safety profile, and optimal usage protocols.

 

 

For more details, see: 

 

Sundra T, Kelty E, Rossi G and Rendle D (2024) 

Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction. 

Front. Vet. Sci. 11:1332337. 

https://doi.org/10.3389/fvets.2024.1332337