Similar but Different: Equine Cushing's Disease and EMS
Photo: Christy M. West
Equine Cushing's Disease and Equine Metabolic Syndrome (EMS) are common endocrine disorders in horses that share some of the same clinical signs, so how do we separate the two conditions?
"It is important to examine the history, animal, and laboratory results when considering endocrine disorders in horses," says Nicholas Frank, DVM, PhD, Dipl. ACVIM, professor of Large Animal Medicine at Tufts University. "Equine metabolic syndrome is likely to have a genetic basis and horses are often obese and have a history of gaining weight on limited calories. They are usually younger when EMS first develops and this condition predisposes them to laminitis. In contrast, horses with Cushing's disease, which is better referred to as pituitary pars intermedia dysfunction (PPID) are middle-aged or aged when clinical signs appear and often have a leaner body condition. "
Management of EMS primarily focuses upon weight control and dietary changes, Frank said. In contrast, the drug pergolide is prescribed to manage Cushing's disease by suppressing the activity of the pars intermedia.
This article aims to make sense of the world of Cushing's and EMS. We'll describe the diseases' primary features, compare clinical signs and available diagnostics, and highlight key treatment differences.
Equine Cushing's disease is a common endocrine (hormonal) disorder that is relatively easy to diagnose in its advanced form because classic clinical signs are present. Affected horses have delayed shedding of the winter haircoat, a long curly haircoat referred to as hirsutism, muscle loss, lethargy, excessive drinking and urination, and sometimes, but not always, laminitis. Horses with advanced Cushing's are usually older (more than 20 years old), so we tend to think of this endocrine disorder as a medical condition of old horses.
However, it is increasingly being recognized that Cushing's disease, which should be referred to as PPID at this stage, begins at a younger age. Early Cushing's has been detected in horses 10 years of age and is more prevalent than previously thought. Horses with early Cushing's have a history of decreased muscle mass, loss of condition on the same diet, reduced performance, or development of abnormal fat deposits.
Further questioning may reveal that the horse has retained its winter haircoat for a few weeks longer than other horses in the barn. Longer hairs that are retained and sometimes bleached by the sun can be found in patches in some horses. Diagnosis of early Cushing's relies heavily upon the history and physical examination. One factor that should be considered is a history of EMS because horses with this syndrome appear to be at greater risk for Cushing's disease, and it may develop at a younger age in these animals.
Owners of horses with EMS should watch for the signs of Cushing's disease as their horse grows older.
Equine Cushing's is caused by enlargement of the region of the pituitary gland referred to as the pars intermedia. Normally, the primary hormone the pars intermedia produces is alpha-melanocyte-stimulating hormone (aMSH). To produce aMSH it synthesizes a large protein called pro-opiomelanocortin (POMC), which is then broken down into other hormones. In the healthy horse POMC becomes aMSH within the pars intermedia.
Dopaminergic neurons in the hypothalamus generally keep the pars intermedia in a suppressed state using an inhibitory neurotransmitter they produce, called dopamine. As the horse ages, these neurons sustain oxidative damage, which causes them to degenerate. This loss of neurons allows cells of the pars intermedia to increase in size and number (hyperplasia), and this, in turn, increases hormone production and release; adrenocorticotropin hormone (ACTH) and other derivatives of POMC are released.
Release of ACTH and other POMC peptides from the pars intermedia causes Cushing's for two reasons: 1) a region that doesn't normally secrete ACTH is secreting it in larger quantities; and 2) this region of the gland doesn't respond to negative feedback (the body's natural response to stabilize and stop secretion). Higher concentrations of ACTH and other hormones leads to the clinical disorder recognized as Cushing's.
Thus, equine Cushing's is quite different than Cushing's in people and dogs. In the latter two species, a tumor in a different part of the pituitary, the pars distalis, results in increased ACTH secretion, which subsequently increases cortisol secretion.
Diagnosing Equine Cushing's
Advanced Cushing's can be diagnosed on the basis of classic clinical signs (i.e., long, wavy hair coat, chronic laminitis, etc.) and confirmed by measuring ACTH concentrations in the blood.
Frank goes on to state that, "The real challenge with Cushing's disease is diagnosing the disorder in its earliest stages, so we recommend two tiers of testing."
The first tier tests for ECD are measurement of resting ACTH concentrations and the overnight dexamethasone suppression test. The veterinarian chooses one of these tests to screen the horse for early ECD according to his/her preference, but recognizes that horses in the earliest stage of the disorder can have negative results.
If a positive result is obtained, the diagnosis has been made and treatment can proceed. However, a negative result is difficult to interpret and leaves the veterinarian with two choices - rechecking again in a few months' time or performing the second tier test.
The thyrotropin-releasing hormone (TRH) stimulation test is recommended as the second tier test because the pars intermedia is stimulated and horses with ECD have an excessive response. This test has is not available everywhere and involves collection of two blood samples for measurement of ACTH concentrations; it is considered by experts to the best test for detecting early Cushing's disease.
If the TRH stimulation test is not available, another new approach is to recheck the ACTH concentration in August, September, or October. Frank explains that "although we previously advised against testing horses for Cushing's in the fall, we can use this natural stimulation test to identify horses with early disease, as long as we use a seasonally-adjusted reference range". These adjusted reference ranges are available now and horses with early Cushing's disease can be diagnosed in the fall when their ACTH concentrations increase more than normal horses in response to season.
The clinician should also measure glucose and insulin concentrations because some horses with Cushing's were previously affected by EMS and remain insulin resistant (have a reduced sensitivity to insulin that decreases the ability of glucose to be transported to body cells from the bloodstream). False positive results can occasionally occur with ACTH concentrations when stress and pain affect results. The veterinarian should be aware of this confounding factor and perform testing appropriately.
The vet performs a DST by taking one blood sample and injecting the horse with a small amount of dexamethasone (a steroid hormone like cortisol) intramuscularly. In normal horses administering the DST will result in a serum cortisol decrease. In contrast, horses with Cushing's are unable to respond appropriately to the dexamethasone and suppress cortisol levels. The vet must make two separate trips to the farm in a 24-hour period, and there are concerns about occasional dexamethasone-induced laminitis. Time of year can affect the DST, with false positive results occurring more often when testing is performed in the late summer and in autumn. Vets should avoid performing the test during these seasons.
While there is no cure for equine Cushing's, owners can manage affected animals via medication and supportive care. The treatment of choice for equine Cushing's is oral administration of pergolide and there is now an FDA-approved form of this drug for horses available under the brand name Prascend (Boehringer Ingelheim).
"Pergolide works by mimicking the action of dopamine and inhibiting hormone production within the pars intermedia and, thereby, lowering circulating ACTH and other hormone levels," explains Frank.
Some horses develop transient anorexia and depression at the start of pergolide treatment; veterinarians address this by reducing the dose and slowly raising it over seven days.
Cushing's researchers recommend supportive care and routine vet examinations. These management measures include clipping excessive hair, examining the horse for wounds or infections, ensuring prompt and thorough treatment of all infections (this can require prolonged use of antibiotic drugs), scheduling routine farrier and dental appointments, routine vaccination, and an appropriate deworming schedule.
Vets encourage owners of Cushing's horses to maintain the horse at a healthy body condition score, and ensure his diet is properly balanced. Well-managed horses can live for many years past diagnosis.
Equine Metabolic Syndrome
In contrast to Cushing's, EMS is both a metabolic and a hormonal disorder that describes horses with:
- Regional adiposity: a "cresty neck," fat pads near the tail head, fat accumulation in the sheath/near the mammary gland;
- Insulin resistance
- Hyperinsulinemia; and
"They are commonly referred to as 'easy keepers' because they can thrive, or even become obese, on a diet that would barely maintain the other horses in the same herd. These horses can become overweight on pasture alone."
Second, EMS is a hormonal disorder because insulin aberrations are present.
As described before, "Insulin resistance is a state in which insulin is not effective or as effective as it should be and glucose is not being taken up by the target cells," he adds.
Over time, the pancreas secretes more and more insulin to control rising blood sugar. "Blood insulin concentrations rise above normal range (hyperinsulinemia) in horses with EMS and they have excessive insulin responses to sugars in their diet," says Frank. Insulin resistance is like an early form of diabetes, but horses remain in this state for years, with only a few animals developing true diabetes mellitus."
Laminitis is also an important feature of EMS in horses. In fact, it is the recognition of chronic laminitis that often spurs an owner or vet to consider EMS as the underlying cause. Laminitis often occurs right after a dietary change (e.g., in the spring when the horse is turned out on lush pastures).
Unlike horses with Cushing's, horses are at risk for developing EMS as soon as they reach maturity. While any breed can be affected, EMS is more commonly observed in ponies and breeds that tend to be metabolically efficient, such as Morgans, Spanish Mustangs, Peruvian Pasos, and Paso Finos.
"Horses prone to EMS likely have some sort of genetic predisposition for the disease," suggests Frank. "For example, these horses have likely evolved in harsh climates and their metabolic systems have been programmed to be highly efficient. As a result, they easily gain weight when fed good quality hay or pasture."
EMS, like Cushing's, typically has an insidious onset, meaning it develops so gradually that it's well-established before becoming apparent. Clinical signs, most notably obesity and/or regional adiposity and laminitis (which is often recurrent or chronic), are usually the tip-off that there might be a problem. In contrast, delayed shedding of the winter hair coat or a long, curly hair coat are the most common clinical signs in horses with Cushing's.
"Diagnosis should be pursued when the horse is not in the midst of a laminitic episode, because pain and stress affect results," advises Frank. Testing for EMS also has two tiers. The first tier test involves measuring glucose and insulin concentrations after a short period of fasting. The horse should be held off pasture in a stall or enclosure and fed only one flake of hay at 10 p.m. the night before testing. A blood sample is then collected the following morning. This is a screening test for hyperglycemia and hyperinsulinemia. If the horse or pony has an abnormally high insulin concentration, we have diagnosed EMS, and no further testing is required.
"Occasionally we detect ... hyperglycemia," notes Frank. "No matter what the insulin concentration is, we consider this to be a more serious situation. Unless hyperglycemia can be explained by pain or stress, we consider it to be an indication of diabetes mellitus, which demands more intensive management. The last scenario encountered is the horse or pony with obvious clinical signs of EMS, such as generalized obesity, a thick, cresty neck, and laminitis, that does not have an elevated glucose or insulin concentration. In this case, we remain suspicious of insulin resistance, but the screening test has failed to confirm the diagnosis. We must then perform a dynamic test."
The latest test to be developed for EMS is the oral sugar test (OST) and this is the second tier test in cases where the resting glucose and insulin concentrations are within referenced ranges. This test examines the horse's insulin response to sugars; in this case corn syrup. A measured dose of corn syrup is given by mouth and then a blood sample is collected between 60 and 90 minutes later. Horses with EMS have higher insulin concentrations than normal horses and cut-off values have been established.
"Although some horse owners have been concerned about the test causing laminitis, more than 500 horses have been tested with only one suspected case of laminitis, that was not confirmed" says Frank.
Like the diabetes solution for obese people, there's a three-pronged "Biggest Loser"-type approach to EMS management:
- Weight loss;
- Dietary changes; and
- Regular exercise.
Believe it or not, most horses can be maintained on a forage-only diet. In fact, EMS horses (typically easy keepers) can become obese even on poor-quality forage. It is important to first recognize what a healthy body weight for your horse is, then feed him appropriately to achieve and maintain this healthy weight.
"Limit or even eliminate concentrates and limit or eliminate access to pasture," advises Frank. "Work with an equine nutritionist. Have your hay analyzed and feed hays with a low sugar and starch content."
Frank also recommends instituting an exercise program to properly manage EMS horses. Specifically, daily or near-daily exercise is advised: hand walking, longeing, long-lining, driving, riding, ponying, or any combination of the above. But don't jump the gun. Keep your newfound enthusiasm for your horse's fitness in check, and ensure he's not currently suffering from a laminitic episode. Institute dietary changes, wait for the episode to resolve (if he is, in fact, battling one), then slowly increase your horse's exercise level.
"For extreme cases that simply cannot be managed by instituting these three changes alone, there is some evidence that levothyroxine (drug to treat low thyroid activity) and metformin (an anti-diabetic drug) are beneficial," relays Frank.
Point of Confusion
One confusing aspect of this topic is that veterinarians sometimes detect insulin resistance in horses with Cushing's disease. According to Frank, "We suspect that horses and ponies with EMS are predisposed to Cushing's disease, and insulin resistance appears to get worse when horses with EMS develop Cushing's later in life."
It is therefore important to check horses with Cushing's for insulin resistance. This problem often improves with Cushing's disease treatment, but the veterinarian should make appropriate dietary recommendations to manage insulin resistance. The owner should consider the carb content of feed, but vets do not recommend calorie restriction for thinner horses. Low-starch/low-sugar pelleted feeds are available.
When it comes to equine metabolic and hormonal disorders, it is not appropriate to shrug our shoulders and think, "Six of one and half a dozen of the other."
"Successful management mandates that we distinguish between the two using all available tools and tests," Frank concludes.
About the Author
Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.