Making Sense of the Cushing's-EMS-Hypothyroidism Puzzle
You've heard the words murmured like catchphrases in the tack room at the barn, by the farrier's truck, and even at Happy Hour amongst your horsey friends. You've always nodded your head in understanding, but after a while it all gets confusing. Once and for all, what is the difference between equine Cushing's disease, equine metabolic syndrome, and hypothyroidism?
Here we'll help make sense of these three conditions.
Pituitary Pars Intermedia Dysfunction (Cushing's Disease)
Commonly known as equine Cushing's disease, pituitary pars intermedia dysfunction (PPID) is a progressive syndrome affecting older horses. Common clinical signs include weight loss; a long, thick hair coat and delayed shedding; increased frequency of drinking/urination; and chronic laminitis (an inflammation of the laminae--the interlocking leaflike tissues attaching the hoof wall to the coffin bone). A loss of muscle mass along the horse's topline and sagging abdominal musculature can also cause the affected horse to develop a pot-bellied appearance.
The condition is thought to arise from age-related chronic oxidative stress (the production of oxygen free radicals that can damage many kinds of tissues), which leads to degeneration of the neurons that inhibit the pars intermedia portion of the pituitary gland (the endocrine gland at the base of the brain that stores and/or secretes many hormones important to body function). This causes the pars intermedia to increase in size (hyperplasia) and overproduce its derivatives, namely adrenocorticotropic hormone (ACTH, which regulates cortisol--the "stress hormone"--secretion). This overproduction causes the adrenal gland to secrete excess cortisol and leads to the horse drinking and urinating more, along with a predisposition to laminitis and, to some degree, insulin resistance (the body's inability to control glucose--or blood sugar--levels with normal amounts of the hormone insulin).
Veterinarians most commonly diagnose PPID in horses by measuring blood ACTH levels in the resting horse and by using the dexamethasone suppression test, whereby the veterinarian obtains a blood sample, gives an injection of dexamethasone, then measures the cortisol level in blood several hours later. This helps detect an ACTH increase or persistently high cortisol levels. However, clinical signs are sometimes more specific indicators of PPID than blood tests.
"Horses with chronic Cushing's disease can have decreased immune function," says Nora Nogradi, DVM, Dipl. ACVIM, a graduate student at Purdue University. "Therefore, we often check resting ACTH levels on our geriatric patients battling chronic infections (pneumonia, sinusitis, or periodontal disease, for example), to see whether underlying Cushing's disease plays a role. In these cases getting the endocrine disorder under control is essential for a successful recovery from the bacterial infection."
There is no cure for PPID, but it can be managed effectively with long-term administration of pergolide (Editor's note: For updated information about FDA-approval of a pergolide drug for horses, please see our March 2012 article "FDA No Longer Supports Compounded Pergolide Production"), which should cause the horse's clinical signs to diminish and diagnostic test results to improve within the first two months of use in 85% and 60% of horses, respectively.1
Equine Metabolic Syndrome
Equine metabolic syndrome (EMS) is a condition of obesity, insulin resistance, and laminitis in horses and, more commonly, ponies. It affects mainly younger horses and ponies from 5 to 15 years of age. Typically, affected horses are classic "easy keepers" (maintaining or gaining weight on a minimum amount of food) that are obese and/or have increased fat (adipose tissue) deposition in the neck (cresty necks), tailhead, and behind the shoulder. This is known as regional adiposity.
Both environmental and genetic factors are thought to contribute to EMS development. Overfeeding, insufficient exercise, and ponies' natural adaptation to survive on very little nutrition in the wild all contribute to obesity. Adipose tissue is associated with decreased insulin sensitivity. Scientists believe the resulting high levels of insulin (which the body produces to regulate circulating glucose levels) impair the digital blood vessels' ability to dilate and respond during times of challenge and, therefore, contribute to laminitis.
Three diagnostic criteria exist to identify a horse with this syndrome: obesity or regional adiposity, predisposition to laminitis, and insulin resistance. Veterinarians might diagnose insulin resistance through resting or dynamic blood tests of insulin levels, provided the horse is not under stress and has not ingested a high-carbohydrate meal recently.
Owners can manage horses with EMS through exercising them regularly (at least 30 minutes a day of riding or longeing) and changing their diets. "While regular exercise is key in managing horses with EMS to improve insulin sensitivity, most horses are diagnosed with this syndrome during an acute flare-up of laminitis," Nogradi explains. "In these cases it is recommended to adjust the diet, care for the feet, and resume the regular exercise regimen when the laminitis is under control."
Dietary modifications to manage EMS should include limiting or eliminating pasture access by using a grazing muzzle or confining a horse to a drylot; restricting/limiting hay intake to 1.5% of the horse's body weight; soaking the horse's hay for 30 minutes to decrease the starch content; and replacing grain with a commercial ration balancer. The latter should provide essential vitamins and minerals to supplement a forage diet without superfluous amounts of carbohydrates. Short-term L-thyroxine (synthetic thyroid hormone) supplementation can help initiate weight loss when necessary. Metformin and pioglitazone are insulin-sensitizing drugs that have been used to improve insulin resistance in humans, but they are still being researched as EMS treatment options.
In years past, veterinarians attributed a syndrome of obesity-associated laminitis (now known as EMS) to hypothyroidism (decreased thyroid function) because ¬affected horses had low thyroid hormone levels in the blood, they responded to thyroid hormone supplementation, and clinical signs were similar to those of dogs with hypothyroidism.
One study has since shown that horses that have their thyroid gland removed do not develop laminitis, however, and another study indicates that the hormonal pathway between the pituitary gland and thyroid gland (pituitary-thyroid axis) was normal when veterinarians performed thyroid stimulation tests on horses with EMS. This means most adult horses do not have primary hypothyroidism (which is a disorder of the thyroid gland itself), but instead have a metabolic disturbance that has caused the pituitary gland to produce less thyroid-stimulating hormone. Treatment with phenylbutazone (Bute, such as for chronic laminitis in EMS) can also falsely decrease thyroid hormone levels.
Insulin resistance in EMS-affected horses does improve when horses are given a thyroid hormone supplement (e.g., L--thyroxine), but this is likely because of its use as a weight loss aid. Thus, this supplement should only be used as a short-term weight loss aid, as it might cause side effects when used long-term. These side effects include hyperthyroidism (thyroid overactivity) in horses with normal thyroid hormone levels prior to supplementation; secondary hypothyroidism when supplementation is discontinued suddenly; and owner reliance on the drug and, therefore, inappropriate EMS management.
According to Mary Durando, DVM, PhD, Dipl. ACVIM, of Equine Sports Medicine Consultants, in Newark, Dela., hypothyroidism is likely overdiagnosed when veterinarians detect low resting thyroid hormone levels, resulting in horses that "are placed on thyroid supplementation without a comprehensive (or accurate) diagnosis, even though they may have normal thyroid glands. Often the reason is vague poor performance, although thyroid disorders may have nothing to do with their performance problems."
True hypothyroidism in the adult horse is extremely rare and is seen more often in foals. Clinical signs include anemia (low red blood cell count); low body temperature, heart rate, and respiratory rate; lethargy; coarse hair coat; and obesity. Hypothyroidism in adult horses usually results from insufficient iodine intake and can be treated with thyroprotein or iodinated casein (a protein found in milk that is used as a binding agent). With treatment, these horses typically start showing improvement in two weeks.
Comparing the Conditions
So why are these three conditions often confused? It's easy to get early PPID and EMS mixed up because both diseases alter cortisol and insulin levels and, therefore, share signs of laminitis, infertility, and fat redistribution. Overlap can also occur as some EMS horses develop PPID over time. Equine metabolic syndrome and hypothyroidism might also be difficult to differentiate due to similar signs of obesity, low thyroid hormone levels, and positive response to L-thyroxine treatment. However, it is important to distinguish between PPID, EMS, and hypothyroidism since treatment for each condition differs greatly.
The best distinguishing factors between PPID and EMS are blood tests (typically measuring ACTH levels), age (average age of 19-21 years for PPID versus 5-15 years for EMS), and obesity (muscle-wasting and weight loss in PPID horses versus generalized or regional adiposity in EMS). Especially early in the disease process, the horse owner's astute observations can help distinguish the two conditions. According to Durando, an owner often "recognizes subtle changes earlier than the veterinarian, who only sees the horse once a year and may not be so familiar with it. In this way (the owner) can help to guide the vet as to early physical changes they may be seeing, and this may help pinpoint the problem earlier or add weight to equivocal lab tests."
Over time, as the disease progresses, PPID can be further distinguished from other conditions by the abnormal hair coat that most affected horses develop. Furthermore, insulin resistance is not a consistent finding in PPID-affected horses. True hypothyroidism is extremely rare in adult horses and can be distinguished from the other two conditions using a thyroid stimulation test.
Endocrine diseases of adult horses can be difficult to sort out. Nogradi emphasizes that "while in most cases the phenotype (physical characteristics) can be suggestive of the disease process, it is always recommended to seek veterinary assistance to achieve accurate diagnosis and initiate the appropriate management/treatment plan." Keep in mind the facts about PPID, EMS, and hypothyroidism so you will not only be well-armed during conversations at the barn but also be able to help your veterinarian arrive at an early diagnosis and develop a treatment plan for your horse.
1. Donaldson MT, LaMonte BH, Morresey P, Smith G, Beech J. Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing's disease). J Vet Intern Med. 2002 Nov-Dec;16(6):742-6.
|AT A GLANCE|
|Equine Cushing’s Disease||Equine Metabolic Syndrome||Hypothyroidism|
|Average age||19-21 years||
|Foals; rare in adults|
|Breed||Any, although prevalent in pony breeds||
Pony breeds, Morgans,
Paso Finos, Arabians, Saddlebreds, Warmbloods
|No breed predisposition|
|Hair||Long, thick, sometimes curly, delayed shedding||Normal||Coarse|
Weight loss, especially along topline; swayback; pendulous (fat distribution)
|Obesity or regional adiposity||Obesity|
|Thyroid test result||High cortisol levels detectable during thyrotropin-releasing hormone stimulation test||Usually low thyroid hormones detectable in the bloodstream, but normal thyroid stimulation test results||Low thyroid hormones in the bloodstream at rest and as a result of thyroid stimulation tests|
|Insulin level||Often high||High||
|Glucose level||Often high||High||
|Gold standard test method||Dexamethasone suppression test||Combined glucose-insulin test||Thyroid stimulation test|
|Appropriate diet||Balanced diet aimed at producing a low glycemic response (small amounts frequently)||Ration balancer, feeding 1.5% body weight in hay, no grass in feed||Minimum 0.1 mg/kg iodine in feed|
|Medications||Pergolide. Also bromocriptine or cyproheptadine (a serotonin blocker)||
L-thyroxine (synthetic thyroid (a dopamine agonist) or hormone), metformin, or pioglitazone (the latter two are
|Iodinated casein or thyroprotein; L-thyroxine|
About the Author
Board-certified in internal medicine. Professional interests include neonatology, respiratory disease, and gastroenterology.
POLL: University Equine Hospitals