The Latest Research in Equine Endocrine Diseases

The Global Equine Endocrine Symposium highlighted new research that continues to broaden the understanding, diagnosis and treatment of equine endocrine diseases.

(Editor’s note: The Global Equine Endocrine Symposium (GEES), shared the latest research in equine endocrine diseases. It was hosted by Boehringer Ingelheim, Inc., which sponsored this coverage of the presentations.)

There were 37 presentations on the diagnosis, treatment and management of equine endocrine diseases during the 5th Global Equine Endocrine Symposium (GEES) held in January 2023 in Bern, Switzerland. Focus was on treatment and monitoring of pituitary pars intermedia dysfunction (PPID, also known as Cushing’s disease) and management of horses with obesity and equine metabolic syndrome (EMS).

The main objective of the Symposium was to review relevant science, including some research that had not been published at the time of the meeting.

The key research topics covered EMS, PPID, testing for metabolic issues and possible new treatments for these diseases.

Diagnosis of Endocrine Disorders

According to the AAEP, the most common equine endocrine disorders are PPID (equine Cushing’s disease) and equine metabolic syndrome (EMS).

It’s fairly simple to notice the horse that has a long, non-shedding haircoat (which is called hypertricosis) often associated with PPID.

hairy pony
A long non-shedding haircoat is often associated with PPID. Diagnosing endocrine diseases when clinical signs are less obvious is more difficult.
© iStock

It can become more difficult to diagnose endocrine diseases when clinical signs are less obvious. Aside from failure to shed properly and a long, curly hair coat, horses with PPID can have increased water intake and urination (polyuria/polydipsia or PU/PD), laminitis (often recurring), hoof abscesses, lethargy, chronic infections, excessive or inappropriate sweating, loss of muscle mass, pot-bellied appearance and reproductive issues.

Equine metabolic syndrome can have some similar clinical signs in horses as PPID, including laminitis. EMS-affected horses also have insulin resistance (IR) and excess fat deposits, especially a cresty neck and fat pads at the tailhead.

There were multiple presentations at the GEES meeting that discussed diagnosis of endocrine diseases. Those discussions centered around ACTH/TRH and insulin (oral sugar) testing.

One presentation discussed PPID and insulin dysregulation (ID) in horse breeds classified by genetic clade (Prevalence of Pituitary Pars Intermedia Dysfunction and Insulin Dysregulation in Horse Breeds Classified by Genetic Clade, authored by Rachel Lemcke, MS, of Amwell Data Services LLC, in New Jersey; Steve Grubbs, DVM, PhD, DACVIM; and Kelly Graber of Boehringer Ingelheim Animal Health USA, Inc.).

This retrospective analysis was performed on veterinarian-provided data from a 2016-2020 study in the United States on 6,266 ponies and horses with suspected endocrine disorders (primarily PPID). This study did not include Quarter Horses or Paints due to the high risk of breed misclassification. The enrolled horses were separated by breed into 13 clades, which is a branch of a genetic cladogram that includes a single common ancestor and all of that individual’s descendants. Several clades included closely related breeds. Frequency of endocrine-associated clinical signs were also compared among endocrine classifications and clades.

The research showed that the highest rates of PPID (61.52%) and insulin dysregulation (72.22%) occurred in Clade 3, which included Miniature Horses, Shetland ponies and dwarf ponies.

The lowest rate of PPID (21.70%) was found in Clade 2 (Lusitano and Andalusian). Clade 7 (Percheron and Belgian Draft) had the lowest rate of insulin dysregulation (24.84%).

In addition, endocrine disorders were identified in over half the horses 10 years old and younger in the majority of clades, highlighting the need for endocrine testing in younger horses.

Overweight pony
Equine metabolic syndrome-affected horses have excess fat deposits, especially cresty necks and fat pads at their tailheads.
iStock-Nigelb

Laminitis was statistically associated with horses that had both PPID and insulin dysregulation, as well as those with insulin dysregulation only. Clades 1 (Peruvian Paso and Paso Fino) and 3 (which included Miniature Horses, Shetland ponies and dwarf ponies) had statistically higher rates of laminitis than several other clades.

Horses in this research were more likely to have both PPID and insulin dysregulation rather than only PPID. In fact, horses were more likely to have only insulin dysregulation or no identified endocrine disorder than only have PPID. (Editor’s note: It is important to note that the majority of these horses and ponies were not tested using dynamic testing, suggesting these frequencies of endocrine disorders might be underestimated.)

This research highlights the continued need to evaluate younger and older horses and ponies with clinical signs for endocrine disorders, preferably using dynamic testing (which is more sensitive than static testing). Testing for only PPID or insulin dysregulation might lead to an oversimplification of the endocrine dynamic within patients, inadvertently allowing undiagnosed endocrine comorbidities to cause further clinical signs and negatively impact horse health.

That same group also reported on Exploring Endocrine Disorders within Warmblood Breeds: Frequency of PPID and ID. This study used the same group of horses as above, but they compared rates of endocrine disorders among nine Warmblood breeds. A second comparison was performed examining the frequency of endocrine-associated clinical signs in three specific Warmblood breeds (Dutch Warmblood, Hanoverian and Oldenburg) versus non-breed-specific Warmbloods.

The study results showed that endocrine disorders were identified in 55-85% of specific Warmblood breeds versus 69% of non-breed-specific. There was not a significant difference in endocrine disorder prevalence among any Warmblood breed evaluated.

Of the three Warmblood breeds compared to non-breed-specific Warmbloods, regional adiposity was the only endocrine-associated clinical sign statistically different among the comparisons. Oldenburgs had a lower rate of regional adiposity regardless of endocrine classification versus non-breed-specific Warmbloods.

Jumper horse
Study results showed that endocrine disorders were identified in 55-85% of specific Warmblood breeds versus 69% of non-breed-specific.
© iStock – K.R. Simon

Among all Warmblood breeds evaluated, regional adiposity rates were highest in Warmbloods with PPID and insulin dysregulation versus those with only PPID.

The researchers noted that, “Hair coat changes were statistically associated with horses with PPID as well as those without endocrine disorders, suggesting many horses in this study may have undiagnosed PPID. Rates of regional adiposity were lowest in PPID-only horses, further highlighting the need for dynamic testing.”

A study titled Muscle Atrophy Scores in a Population of Aged Horses and Ponies With and Without PPID was reported on by Pat Harris MA, PhD, DipECVCN, VetMB, MRCVS. She is head of the Equine Studies Group at Waltham Petcare Science Institute in the United Kingdom and Director of Science for Mars Horsecare.

Harris shared recent survey results from more than 2,000 owners of senior horses in the USA. The survey had been carried out in collaboration with the Gluck Equine Research Center in Kentucky. The owners had reported that nearly 20% of their older horses had low muscle mass. While age was a major contributor, PPID was also an important risk factor.

Harris also introduced the new Muscle Atrophy Scoring system (MASS) that had recently been developed for use in horses by the Gluck Equine Research Center in collaboration with Waltham. She explained that this required users to first determine for each of the assessment areas whether the lean MASS or the adipose MASS scoring chart should be used in order to minimize any confusion between adipose tissue and muscle.

Harris went on to describe in more detail the study undertaken in collaboration with Melbourne University the Queensland University of Technology and Boehringer Ingelheim.

In her conclusions, Harris stated: “The results confirm that muscle atrophy is a common feature of PPID; and that the scoring system developed in horses is also applicable to ponies, including Shetland/Miniature ponies. The majority of non-PPID animals (of a similar age to the PPID group) showed no evidence of muscle atrophy, indicating that old age per se is not automatically associated with muscle loss in healthy animals. PPID appears to be associated with a specific loss of muscle tissue. These findings warrant may have important implications for optimizing the nutrition of horses and ponies with PPID.”

She emphasized that the MASS could be an important muscle atrophy monitoring tool for owners and veterinarians, although she recommended concentrating just on the neck, back and hindquarter regions.

New and Possible Treatments

There were several exciting presentations that offered initial research on medicines used to treat insulin dysregulation in horses. The specific drugs that were researched were velagliflozin (researched for horses) and canagliflozin (Invokana® for humans).

Velagliflozin and canagliflozin are both sodium-glucose co-transport 2 (SGLT2) inhibitors that reduce renal glucose reabsorption, promote glucosuria, and consequently, decrease blood glucose and insulin concentrations.

In horses, velagliflozin has been researched to counteract the effects of insulin dysregulation, including the development of laminitis. The study presented at the GEES meeting was The sodium-glucose cotransporter-2 inhibitor velagliflozin decreases basal plasma insulin concentrations in horses with moderate-severe insulin dysregulation and was presented by Kristen Thane, DVM, DACVIM (Large Animal), of Tufts. She noted that velagliflozin decreased plasma insulin concentrations in horses with moderate/severe hyperinsulinemia. She said that serum triglyceride concentrations increased in all horses treated with velagliflozin. This hypertriglyceridemia typically improved gradually during the 40-week trial.

Development of marked hypertriglyceridemia was observed in some horses after starting treatment with velagliflozin. Therefore, serum triglycerides should be monitored when initiating therapy with an SGLT2 inhibitor. No laminitis developed while horses were receiving velagliflozin treatment.

Canagliflozin in previous research showed it had the ability to lower insulin levels in horses, reverse or reduce fat pads and eliminate laminitis pain in horses with refractory hyperinsulinemia and laminitis.

Understanding PPID

The study Factors influencing owner decision-making regarding the management and treatment of pituitary pars intermedia dysfunction was presented by Jo L. Ireland, BVMS, PhD, Cert AVP(EM), FHEA, FRCVS, of the University of Liverpool’s School of Veterinary Science. This study investigated owner understanding of PPID and treatment. What the study found was that:

• Where horses were not exhibiting typical signs of PPID, the disease became “abstract and difficult to comprehend.”

• Owners with horses that had concurrent health issues such as EMS and PPID found it difficult to differentiate between the diseases.

• Owners believed they knew their horses best.

• Balancing management and treatment was complex, i.e., for weight management horses need to be kept off grass but if they had arthritis then movement was needed.

• Owners wanted horses to have time to be out with other horses.

• The vet-owner relationship was important in the care of the horse.

• Small improvements in veterinary-to-owner communication could have a large impact on treatment compliance.

• Cost of treatment was not the main consideration, but it was a concern.

• Health and happiness go hand-in-hand, and owners think horses can’t have one without the other.

• The perceived risk of laminitis was troubling to owners.

Long-Term PPID Treatment

The study Long-Term Response of Equids with Pituitary Pars Intermedia Dysfunction to Treatment with Pergolide was presented by Hal Schott, DVM, DACVIM, of Michigan State University. He said PPID is being increasingly recognized and treated. However, there is limited data on long-term response to treatment with pergolide.

This study determined that long-term treatment of equids with PPID produced clinical improvement in nearly all affected animals. However, horses might not need progressively increasing drug doses. Endocrine test results can improve in PPID horses treated with pergolide over a prolonged period of time. Treatment with pergolide improves the quality of life but does not prolong life.

Schott said that overall, there is high client satisfaction with extended use of
Prascend® (pergolide tablets).

Management of Obesity and EMS

Alfredo Sanchez-Londoño, DVM, MS, DACVIM (Large Animal), of Auburn University, created a web-based Survey of Knowledge of Equine Endocrine Diseases by Horse Owners. A total of 1,972 respondents completed the survey, the vast majority of which were based in the United States. Of that total, 1,286 participants were familiar with the term PPID, 679 were not and 7 did not respond. From the 1,972 participants, 955 had heard about PPID and EMS but had not had a horse diagnosed with either, 511 had a horse diagnosed with PPID, 251 had a horse diagnosed with both EMS and PPID, and 202 had a horse diagnosed with EMS.

Take-Home Message

Researchers have provided much-needed new information about endocrine diseases in equids in recent years. More research is being conducted, but it is hard for busy veterinarians, farriers and owners to get that new information and put it to use.

For more information from the 2023 GEES meeting, search for an article on EquiManagement.com titled “Key Takeaways from the 5th GEES” and download the Proceedings from the 5th Global Equine Endocrine Symposium

IMPORTANT SAFETY INFORMATION: PRASCEND treatment may cause loss of appetite. Most cases are mild. Adverse reactions may occur if animals other than horses ingest PRASCEND tablets. Not for human use. Do not ingest the product. Refer to the package insert for complete product information.

PRASCEND® is a registered trademark of Boehringer Ingelheim Vetmedica GmbH, used under license. ©2023 Boehringer Ingelheim Animal Health USA Inc., Duluth, GA. All Rights Reserved. US-EQU-0114-2023

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