Focal points of the 5th Global Equine Endocrine Symposium (GEES) held in January 2023 in Bern, Switzerland, were diagnosis of endocrine diseases, treatment and monitoring of pituitary pars intermedia dysfunction (PPID) in the daily routine, and management of horses with obesity and EMS. In this article, we will highlight some key takeaways from the 37 presentations and multiple discussions at GEES. The main objectives of the Symposium were to review relevant science, including some research that had not been published at the time of the meeting.
(Editor’s note: The GEES meeting is hosted by Boehringer Ingelheim, Inc., which sponsored this coverage of the presentations.)
Key discussions at the GEES meeting centered around equine metabolic syndrome (EMS), PPID, ACTH (adrenocorticotropic hormone, which is released from the pituitary gland), thyrotropin-releasing hormone stimulation test (TRH is a hormone synthesized in the hypothalamus that stimulates secretion of thyroid-stimulating hormone—TSH—by the anterior lobe of the pituitary gland), leptin (a hormone expected to be increased in EMS horses), and insulin (insulin levels are used to determine if a horse is considered insulin dysregulated and at a higher risk of laminitis, such as in horses with EMS and approximately 30-47% of PPID horses).
These key takeaways from GEES are available for download here.
Diagnosis of Endocrine Disorders
According to the AAEP, the most common endocrine disorders dealt with today by equine practitioners and owners are pituitary pars intermedia dysfunction (PPID or equine Cushing’s disease) and equine metabolic syndrome (EMS).
It’s fairly simple to find the horse that has hirsutism (long, non-shedding haircoat) or hypertricosis often associated with PPID. (Editor’s note: Hypertricosis is considered the more correct term for acquired increase in hair length and lack of shedding that often occurs when horses have disease of the pars intermedia.)
It can become more difficult when signalment of endocrine disease is less obvious or specific. 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 usually 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 at GEES 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).
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 both the highest rates of PPID (61.52%) and ID (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 ID (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.
Decreased athletic performance was not statistically associated with any endocrine classification or combination evaluated, although it was less prevalent in Clade 2 than in Clade 6 (Clydesdale and Shire).
Laminitis, however, was statistically associated with horses that had both PPID and ID, as well as those with ID only. Clades 1 (Peruvian Paso and Paso Fino) and 3 had statistically higher rates of laminitis than several other clades.
Horses in this data set were more likely to have both PPID and ID rather than only PPID. In fact, horses were more likely to have only ID or no identified endocrine disorder than only have PPID. 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 for equine practitioners 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 ID might lead to an oversimplification of the endocrine dynamic within patients, inadvertently allowing undiagnosed endocrine comorbidities to cause further clinical signs and negatively impact patient health.
This work can also help inform veterinarians of likelihoods of endocrine disorders within a variety of specific horse and pony breeds.
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 This 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.
Among all Warmblood breeds evaluated, regional adiposity rates were highest in Warmbloods with PPID and ID versus those with PPID alone. Rates of decreased athletic performance and laminitis were not statistically associated with any endocrine classification.
Therefore, veterinarians who work with Warmbloods should be on the lookout for PPID and/or ID in their patients and utilize dynamic testing methods. 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 Ages Horses and Ponies With and Without PPID was reported on at GEES 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, as background information, some 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. She 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 (Herbst et al 2022). 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, together with the Queensland University of Technology and Boehringer Ingelheim. This evaluated, in Australia, the utility of the new MASS in a group of 31 animals (18 ponies and 13 horses more than 15 years old) with and without PPID. A PPID-positive diagnosis was established in 12 animals based on clinical signs, baseline ACTH and a TRH stimulation test.
All animals were assessed and body condition (BCS: 1-9), cresty neck (CNS: 0-5) as well as MASS (4-1: using lean or adipose charts as appropriate) scores were obtained.
Overall, the PPID animals had significantly more muscle atrophy than the non-PPID animals. The majority of the non-PPID animals showed no signs of muscle atrophy. Seven of the PPID animals had a MASS of 7 or more. Only one non-PPID animal had such a value (a 32-year-old mare with marked atrophy and chronic weight loss). These differences in MASS were found despite there being no overall difference in BCS or CNS between the two groups.
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. As the PPID animals had similar BCS and CNS to the non-PPID cohort, there appears to be no loss of adiposity due to this condition (assuming they are otherwise healthy). Rather, PPID appears to be associated with a specific loss of muscle tissue. These findings warrant further investigation and may have important implications for optimizing the nutrition of horses and ponies with PPID.”
She emphasized that the MASS therefore could be an important muscle atrophy monitoring tool for owners and veterinarians, although she recommended concentrating just on the neck, back and hindquarter regions.
Veterinarians examining older horses and ponies should pay specific attention to monitoring muscle atrophy, especially in animals with, or suspected of having, PPID. [For more information on the MASS scoring system see Herbst, A.C.; Johnson, M.G.; Gammons, H.; Reedy, S.E.; Urschel, K.L.; Harris, P.A.; and Adams, A.A. 2022 Development and evaluation of a muscle atrophy scoring system (MASS) for horses. JEVS, p.103771.]
New and Possible Treatments
There were several exciting presentations at GEES 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. However, 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.
At the GEES meeting, Drs. Sanna Lindase and Johan Brojer of the Department of Clinical Sciences, Swedish University of Agricultural Sciences, each presented on studies looking at canagliflozin.
Lindase noted that short-term treatment with canagliflozin decreased excessive hyperinsulinemia 65% compared to placebo, but there were no differences between the study doses (0.6 vs 1.2 mg/kg). The horses treated with canagliflozin decreased in body weight and had higher serum triglyceride concentrations. She could not find a correlation between decrease in body weight and increase in triglyceride concentrations.
Brojer studied how canagliflozin affected the beta-cells in the pancreas compared to placebo. The striking finding was that canagliflozin changed the function of the beta-cells. He concluded that the marked decrease in insulin response seen in insulin dysregulated horses treated with canagliflozin is caused by lower blood glucose concentrations since glucose is lost by urine, but more importantly, because the beta-cells produce less insulin in response to increases in blood glucose concentrations.
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.
The study Long-Term Response of Equids with Pituitary Pars Intermedia Dysfunction to Treatment with Pergolide was presented at GEES 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. 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). He said most owners are willing to spend $1,000 annually to treat horses, but that willingness drops off at $1,500 per year.
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 Farriers/Hoof Professionals. The survey was distributed world-wide through farrier associations, farrier magazines and social media. Of the 179 participants who completed the survey, 141 were familiar with the term PPID and all of those had heard of equine Cushing’s disease.
A total of 167 were familiar with the term EMS, and all respondents were familiar with the term “easy keeper.” Since foot maintenance is critical in managing horses affected with PPID or EMS, farriers were asked about owner compliance with those issues. It was considered “good” for 72 respondents and “average” compliance by 57.
The foot care professionals said emphasis needs to be on prevention of EMS. Many recommended boots in the acute phase of laminitis. There needs to be more basic information available for horse owners. Owner compliance is good initially, “but then they go backward.” He said more vets should be working together with farriers, and that veterinarians should talk with horse owners about diet and nutrition of their horses.
The same researcher conducted a 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 1972 participants, 955 had heard about the diseases but had not had a horse diagnosed with them, 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.
Sanchez-Londono said owners want earlier diagnoses of these diseases. They also want other treatments/management strategies for affected horses. There is need for more information about these diseases in donkeys, plus education on nutritional management in all equids. In “other” responses on this survey, there were write-in comments from about 250 owners who felt their veterinarians needed to be more “up-to-date” on information about these diseases.
There is a lot that is and is not known about endocrine diseases in equids. 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.
Veterinarians should be in the forefront of educating themselves, their lay colleagues and their clients about updates in diagnosing, treating and long-term care and management of equids that have endocrine disease.
For more information from the 2023 GEES meeting, download the Proceedings from the 5th Global Equine Endocrine Symposium.
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