Summary of equine endocrinology research updates from 2025 papers

Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) are the two common endocrine disorders that affect horses, ponies and donkeys worldwide.

Insulin dysregulation (ID) is the key feature of EMS and hyperinsulinaemia is thought to cause laminitis in animals with EMS and PPID. PPID is a neurodegenerative disorder whereby there is oxidative damage to the hypothalamic dopaminergic neurones that provide inhibitory input to the equine pars intermedia region of the pituitary.

Loss of this inhibition results in increased production of the pro-opiomelanocortin-derived hormones by this region. This overproduction of hormones results in a wide range of clinical signs, and a diagnosis is made by measuring basal adrenocorticotropic hormone (ACTH) concentrations or ACTH concentrations in response to thyrotrophin-releasing hormone (TRH).

The exact underlying cause of ID in animals with EMS and PPID is unknown, but genetics, epigenetics, obesity, diet and the microbiome all appear to play a role. ID results in an increased risk of laminitis, and a diagnosis is made by identification of basal hyperinsulinaemia, an excessive insulin response to carbohydrate and/or tissue insulin dysregulation.

Since PPID and EMS are common diseases that occur worldwide and are both associated with clinical signs that can have a significant negative impact on welfare and quality of life, they continue to be the focus of a considerable amount of research. A summary of clinically relevant papers published in 2025 to date is provided.

Summary of relevant papers

Endocrine disease in sport horses versus non-sport horses

While leisure (non-sport) horses are frequently tested for both PPID and ID, the prevalence of endocrine disease in sport horses has not been widely reported.

Davis et al (2025) used initial and follow-up submissions to a UK commercial laboratory to determine how widespread endocrine conditions are within sport horses used for athletic purposes, including eventing, dressage and showjumping compared to non-sport horses used for leisure1.

Within the initial samples, PPID and obesity were found to be as prevalent in the sport horse population, but non-sport horses were more likely to have ID. Within the follow-up samples, PPID and obesity were more prevalent in sport horses and ID was more prevalent in the non-sport population.

Conclusion

Screening for endocrinopathies should be considered in sport horses presenting with poor performance.

Plastic versus glass tubes for blood collection when measuring ACTH concentrations

Glass reportedly binds ACTH, but the clinical relevance of using glass blood tubes for measuring equine ACTH concentrations is controversial.

A study compared ACTH concentrations when blood was collected into glass and plastic EDTA tubes at the same time from nine horses (four with PPID and five controls)2.

Samples were centrifuged immediately or stored in the collection tube at 4°C for two, four or six hours before centrifugation. Plasma was separated and ACTH concentration was immediately measured on a chemiluminescent assay. Neither tube type nor storage time had a significant effect on plasma immunoreactive ACTH concentration.

Conclusion

When stored at 4°C as whole blood for up to six hours, equine ACTH concentrations do not significantly differ when blood is collected into glass tubes compared to plastic tubes.

Development of a stall-side ELISA for measurement of ACTH

Measurement of plasma ACTH concentrations for the diagnosis of PPID is complicated by pre-analytical variables that can affect concentration, including sample storage, handling and time to analysis.

A new study reports the development of an ELISA for ACTH measurement that could ultimately form the basis for a stall-side equine ACTH test3. The ELISA was shown to reliably detect rat recombinant ACTH.

Conclusion

A stall-side equine ACTH test may be available in the future.

Effect of breed on ACTH and insulin concentrations

The most commonly used diagnostic test for PPID is documentation of increased plasma ACTH concentrations. However, several studies have demonstrated that healthy mixed-breed ponies have increased circulating concentrations of ACTH compared with horses^4,5.

Evidence also shows breed differences in insulin sensitivity⁶.

A new study compared ACTH and insulin concentrations in quarter horses and Welsh ponies in spring and autumn and found that ACTH and insulin concentrations were higher in horses compared to ponies in autumn and insulin concentrations were higher in autumn compared to spring within the ponies⁷.

Conclusion

Breed should be considered when interpreting ACTH and insulin concentration results.

Long-term response to treatment with pergolide

The long-term response results from the original field clinical efficacy study for Prascend (pergolide; Boehringer Ingelheim has been published.

A group of 30 horses and ponies with PPID were enrolled in an extended treatment study and animals were re-assessed at set time points until death or euthanasia over a period of 14.5 years⁸.

Five animals died and 24 were euthanised (five for chronic laminitis) during the study period (median survival time, 3.6 years; range 0.6–10.5 years); 7 of 13 animals had a dosage increase to 4 µg/kg PO q24h (maximum study dose) between 1.7 to 4.7 years of the study. After 5.5 years, owners of 13 surviving equids reported sustained clinical improvement and endocrine test results normalised in 75%. After 9.5 years of treatment, only two of six surviving equids had normal endocrine test results.

Conclusion

Long-term treatment of PPID-affected equids with pergolide produces clinical improvement in nearly all affected animals and normalisation of endocrine test results in some cases.

Furthermore, this extended treatment study determined that equids can respond favourably long-term to the initial pergolide dose, rather than needing a progressive increase in dose over time.

Effect of pergolide treatment on ID

ID appears to be the cause of laminitis in animals with PPID. Dopamine has been shown to attenuate glucose-stimulated insulin secretion in other species by acting on pancreatic receptors, thus it is possible that the dopamine agonist pergolide could reduce hyperinsulinaemia and improve ID in animals with PPID.

When 16 horses and ponies, comprising 8 matched pairs (PPID+ID or ID-only), were given pergolide at a dose of 2µg/kg bodyweight orally once daily for 4 weeks, pergolide treatment did not alter any of the variables derived from a combined glucose and insulin tolerance test (CGIT), but the insulin response to a carbohydrate meal was reduced in the PPID+ID group⁹.

Conclusion

Pergolide has no effect on tissue insulin sensitivity, but may limit postprandial hyperinsulinaemia in animals with PPID and ID.

Influence of PPID on reproductive performance in Thoroughbred mares

PPID is an age-related disease considered to have a negative impact on fertility. To understand the true impact of PPID on fertility, the influence of age must be considered.

A study of 322 Thoroughbred mares aged 10-20 years aimed to assess the impact of PPID on fertility while accounting for the effect of ageing¹⁰.

The study found that fertility decreased with age in animals with PPID, but not in non-PPID mares and treatment with pergolide did not significantly improve fertility in mares with PPID.

Conclusion

PPID negatively impacts fertility, and this is not improved with pergolide therapy.

Gut microbiota in animals with PPID

Although the links between gut microbiota and neurodegenerative diseases are unclear, the presence of misfolded α-synuclein aggregates in the enteric nervous system has been associated with intestinal inflammation and increased gut permeability in people with Parkinson’s disease.

Such intestinal changes are associated with a shift in gut microbiota with decreased abundance of short-chain fatty acid-producing taxa.

This shift plays an important role in the pathogenesis of Parkinson’s disease by promoting the characteristic ascending neurodegenerative spread of misfolded α-synuclein aggregates from the enteric nervous system to the brain.

PPID in horses is also characterised by the accumulation of misfolded α-synuclein aggregates in the pituitary pars intermedia, thus the effect of PPID on the faecal microbiota was investigated in 9 horses with PPID and 13 age-matched controls¹¹. The abundance of some bacteria was increased and of others decreased in horses with PPID.

Conclusion

The faecal microbial composition is altered in horses with PPID, and the microbiota-gut-brain axis may play a role in the pathogenesis of PPID.

Objective assessment of quality of life in animals with PPID

The clinical signs of PPID are frequently mistaken for “normal” ageing and their impact on an individual animal’s quality of life (QoL) may not be optimally assessed.

Objective QoL assessment could improve clinical decision-making relating to treatment and/or euthanasia. A tool comprising 37 questions has been developed to calculate a QoL score for animals with PPID. Horses with PPID had a worse QoL score compared to non-PPID animals and PPID horses with another chronic disease had worse QoL scores compared to PPID animals without another chronic disease.

Conclusion

The quality of life of animals with PPID can be objectively assessed using an online tool and this could be used to assess the impact of treatment and/or changes in QoL over time.

The effect of pasture consumption and obesity on ID and adiponectin concentrations

ID and hypoadiponectinaemia are risk factors for laminitis and they are sometimes, but not always, associated with obesity.

The effect of pasture-induced weight gain across 12 weeks and maintained obesity for a further 12 weeks on ID and circulating total adiponectin concentrations was determined in non-laminitic UK native breed ponies.

Basal insulin concentration did not change significantly during the study, but post-oral sugar test (OST) insulin concentrations were increased, and insulin tolerance test (ITT) results were decreased at certain time points. Low IIT results coincided with the grass being either short and stressed or long and lush grass. Adiponectin concentrations decreased in all ponies and were significantly lower from week 10 onwards.

Conclusion

Pasture-induced obesity was associated ID at some point during the study in all ponies, but ID status varied throughout the study, sometimes changing from week to week, although these changes were not consistent across ponies. In addition, all ponies showed hypoadiponectinaemia during the study.

Effect of phenylbutazone on insulin sensitivity in animals with ID

Laminitis in animals with ID is frequently managed using phenylbutazone. Previously, it has been shown that phenylbutazone reduces blood glucose and serum insulin concentrations in animals with ID after an oral glucose test¹².

A further study has shown that phenylbutazone reduces insulin concentrations in horses with ID by modulating tissue insulin sensitivity¹³.

Conclusion

The relevance of phenylbutazone in the management of ID extends beyond laminitis-associated pain.

Dapagliflozin treatment in horses with hyperinsulinaemia

In humans, there are differences in pharmacological effects between SGLT2i due in part, to differences in SGLT2/SGLT1 receptor selectivity.

Drugs such as ertugliflozin, are highly selective for the SGLT2 receptor, while dapagliflozin and canagliflozin are less selective for SGLT2 versus SGLT1 than ertugliflozin (approximately 1,000 to 2,000-fold). Ertugliflozin is commonly prescribed for horses, but is not available in some countries.

Canagliflozin and dapagliflozin are more widely available globally as human tablet preparations. A recent horse-owner survey reported that dapagliflozin was prescribed to manage hyperinsulinaemia-associated laminitis, but there are no published studies investigating its use in horses.

A retrospective study evaluated blood parameters in horses treated with either ertugliflozin (0.05mg/kg; n=24) or dapagliflozin (0.02mg/kg; n=34) orally once daily¹⁴.

Both drugs results in significant decreases in basal insulin and lameness grade and increases in triglyceride concentrations from baseline after 7 and 30 days and there was no significant difference in the effects of the two drugs.

Conclusion

Dapagliflozin reduces insulin concentrations and improves lameness to a similar degree as ertugliflozin. Side effects were noted with both drugs, emphasising the need for close monitoring during treatment.

This article appeared in Vet Times (2025), Volume 55, Issue 40, Pages 6-12