Suspect EMS Syndrome

I have one vet telling me PPID not likely, and another telling me suspected PPID. In the lab results, there is this comment (below) relative to the Leptin level which is high at 24.83. (See below) I’m reading this as PPID is more likely if the Leptin level is low in conjunction with high ACTH and high Insulin. My vet is pointing to EMS, but ruled out PPID. (She is very young and new. I’m sure competent, but probably doesn’t have as much experience under her belt.) We have ordered Levothyroxine to help her lose weight. What happens if I give her Pergolide, and she doesn’t have PPID? Is Pergolide required, or can we proceed with diet and exercise changes and see if that is effective? Also, attached is this mare as a yearling, so being hairy is definitely part of her DNA. Like I said, she does shed out normally, but is a beast during the winter. She has NOT foundered.

Normal levels are 1-10 ng/mL; intermediate levels are 10-20 ng/mL; and high levels are >20 ng/mL. Friesians and other draft or light draft-type horses appear to have a higher normal range than light horses in a limited study. The light draft normal range is < 15 ng/mL. In Equine Metabolic Syndrome (EMS), the concentration of leptin is generally in the high or intermediate reference range. Horses with Pituitary Pars Intermedia Dysplasia (PPID, Cushing’s syndrome) with high ACTH and high insulin, but low leptin are more likely to have hyperinsulinemia caused by PPID rather than EMS. High leptin levels alone do not mean a horse has EMS, it may indicate an increased potential for developing EMS and/or the horse is overweight or obese. Ideally leptin levels will decrease as animals are treated for EMS. Leptin levels generally decrease 1-2 months before insulin levels in these horses

Thank you for your response. We may be splitting hairs. I believe that her lameness was the beginning of laminitis, but she does not appear to be in any pain at this time. Nor do I see any evidence of a laminitis episode. There are no x-rays to prove that there is no rotation, though. I trimmed a foundered horse for almost 30 years, so usually the new hoof coming out of the coronet band tells the story without x-rays. I’m not seeing any new growth yet that points to any structural changes.

Your response has confirmed my confusion over the comments by the lab, my vet, the other vet, etc. There does appear to be some gray here. Especially, with the ACTH levels even fluctuating by season.

I asked GROK. Musk’s new AI engine and ChatGPT. You might be interested in the results:

GROK:

Based on the provided levels for this 20-year-old Friesian horse:

ACTH (Adrenocorticotropic Hormone): The level of 48 pg/mL is significantly elevated. Normally, ACTH levels should be below 35 pg/mL, and a level above this threshold could indicate pituitary pars intermedia dysfunction (PPID), commonly known as equine Cushing’s disease. However, seasonal influences should be considered, as ACTH levels can naturally rise in the fall months, particularly in November, when this test was conducted.
Insulin: An insulin level of 45.6 μIU/mL suggests insulin resistance, especially since this horse was not fasted. A fasting insulin level above 20 μIU/mL is indicative of insulin dysregulation, and this horse’s level is considerably higher, reinforcing concerns about insulin resistance or metabolic syndrome (EMS).
Glucose: A glucose level of 90 mg/dL is within the normal range for horses, but in the context of high insulin, it indicates a compensatory mechanism where the horse’s body is still managing to keep glucose levels normal despite insulin resistance. However, this could be a precursor to more severe glucose dysregulation if not managed.
Leptin: With a leptin level of 24.83 ng/mL, there’s an indication of leptin resistance, common in obese horses. Leptin is produced by adipose tissue, and high levels suggest that the horse’s body is not responding effectively to this satiety hormone, leading to continued hunger and overeating, exacerbating obesity.

Interpretation and Considerations:

Overweight and Acorn Consumption: The horse’s condition of being overweight and having consumed a large amount of acorns (which are high in tannins and can affect gastrointestinal health) complicates the interpretation of these results. Acorns can cause changes in the horse’s metabolic profile, potentially leading to increased insulin and ACTH levels due to stress or digestive upset.
Management:
Diet: The horse should be on a low non-structural carbohydrate (NSC) diet to manage insulin resistance. The consumption of acorns should be controlled or eliminated due to their toxicity in large amounts.
Exercise: If possible, increasing exercise can help with weight management and insulin sensitivity.
Medical Treatment: For PPID, pergolide might be considered, but only after confirming the diagnosis with additional tests like a TRH stimulation test, as high ACTH can also be seasonal. For insulin resistance, dietary management is key, but in some cases, medications like metformin might be discussed with a vet.
Further Testing: Since this horse was not fasted, retesting after a controlled fasting period might provide a clearer picture of insulin dynamics. Additionally, considering the season, a TRH stimulation test could differentiate between seasonal ACTH elevation and true PPID.

This scenario underscores the importance of a comprehensive approach involving dietary changes, monitoring, and potentially further diagnostic testing to manage this horse’s health effectively.

ChatGPT:

These laboratory values, paired with the horse’s clinical context (a 20-year-old, overweight Friesian consuming acorns in November), raise significant concerns. Let’s analyze each parameter:

1. ACTH (48 pg/mL):
Interpretation:
ACTH levels naturally rise in the fall (August–November) as part of seasonal variations in pituitary function. A level of 48 pg/mL may still fall within the normal range for this time of year, but it’s borderline and should be interpreted in light of clinical signs (e.g., abnormal hair coat, excessive drinking/urination, weight changes).
Given the age (20 years) and breed (Friesians are predisposed to metabolic conditions), PPID (Pituitary Pars Intermedia Dysfunction) should remain on the differential list. A TRH stimulation test could help confirm or rule out PPID.
2. Insulin (45.6 μIU/mL):
Interpretation:
This is elevated compared to normal fasting insulin levels (<20 μIU/mL). While the horse was not fasted, the level still suggests insulin dysregulation.
Insulin dysregulation is a hallmark of Equine Metabolic Syndrome (EMS), especially in overweight horses. This value warrants further dynamic testing, such as an oral sugar test, to evaluate the horse’s insulin response.
3. Glucose (90 mg/dL):
Interpretation:
Glucose levels are normal (60–120 mg/dL in horses). However, a normal glucose level paired with elevated insulin suggests compensated insulin resistance—the horse can still maintain normal glucose levels by overproducing insulin.
4. Leptin (24.83 ng/mL):
Interpretation:
This is significantly elevated (normal leptin levels are <7–10 ng/mL). High leptin levels are a sign of leptin resistance, which often accompanies obesity and EMS.
Leptin resistance also indicates disrupted energy balance and suggests that this horse’s adipose tissue is metabolically active, contributing to systemic inflammation and insulin dysregulation.
Acorn Consumption:
Acorns are high in tannins and can be toxic, potentially causing gastrointestinal upset (colic, diarrhea) and renal damage. While these lab results do not directly indicate acorn toxicity, any signs of lethargy, colic, diarrhea, or abnormal urination warrant immediate veterinary attention.
Breed-Specific Considerations:
Friesians are predisposed to metabolic issues, including insulin dysregulation and PPID, making these findings particularly concerning in this breed.
Recommendations:
Management:

Dietary Changes:
Eliminate access to acorns immediately.
Transition to a low-sugar, low-starch diet with forage tested for non-structural carbohydrates (NSC <10%).
Provide measured hay rations to encourage weight loss (1.5% of ideal body weight per day).
Exercise:
If no signs of laminitis, implement a gradual exercise program to enhance insulin sensitivity.
Diagnostics:

Conduct a TRH stimulation test to investigate PPID.
Perform a dynamic insulin test (e.g., oral sugar test) to assess the severity of insulin dysregulation.
Evaluate renal function and liver enzymes to check for acorn toxicity effects.
Monitoring:

Check for clinical signs of laminitis (heat in hooves, shifting weight, reluctance to move).
Monitor body condition score (BCS) and adjust feeding plans accordingly.
Treatment Options:

If PPID is confirmed, consider starting pergolide.
For EMS, focus on weight reduction and managing insulin resistance through diet and exercise.
Would you like more details on any of these aspects, such as specific diet plans or testing protocols?

I was surprised at how detailed and thorough the AI responses were. Thank you for your advice on PPID. Happy Holidays! Laurie

So I’ve read now what state the horse should be in to take these tests. No sweet feed. No stress, etc. Well, my horse had Triple Crown Senior which does include molasses within 12 hours and as late as the trailer ride to lure her into the trailer. She was also throwing a fit at the vet which we trailored to. We had to put a lip chain on her to pull the blood. I’m guessing we need to start over with our baseline testing. Given the seasonal issues, what is the best time of year to test for ACTH and insulin?