What is Cushing's Syndrome?
Cushing’s Syndrome is a hormone disorder created by a hyper-stimulated pituitary gland over- communicating with the adrenal glands, which cause high levels of cortisol in the blood. Cushing’s Syndrome exists in the endocrine system, which is comprised of glands that secrete hormones into the bloodstream to regulate the body. These hormones control metabolism, mood, tissue function, and development. An unhealthy endocrine system will lead to serious health problems.
Cushing’s is often mislabeled as a disease; however, most horses progress along a spectrum from the first symptom to the final stage of actual destruction of structures in the body. Therefore, it makes more sense to discuss identifying symptoms and treating horses for Cushing’s as a syndrome before it progresses to the final stage where disease ravages the body.
Cushing’s Syndrome in horses, also referred to as PPID (Pituitary Pars Intermedia Dysfunction), is a result of an overactive pituitary gland. The pituitary gland, located in the base of the brain, is considered the ‘master gland’. It regulates hormone production and release, which controls many body functions. With Cushing’s Syndrome, this gland becomes neurotic due to being bombarded with stress creating inflammation in the body. At this point, the pituitary gland continually signals the adrenal glands, never allowing either gland to switch off.
The excessive amount of hormones released from the pituitary gland causes the adrenal glands (situated over the kidneys) to overproduce cortisol, creating a variety of health issues. The over-abundance of cortisol negatively affects all the normal functions it performs: breaking down of carbohydrates; counter-balancing of insulin levels; regulating nerves, muscle and connective tissue; supporting the immune system; and normalizing blood pressure. Also, when the body is under stress, cortisol is used to attack inflammation.
It may take years for an owner to recognize the group of symptoms being presented. As the number of symptoms accumulate, or as the intensity of symptoms increase, the horse exhibits an unhealthy appearance. It is important to identify Cushing’s as early as possible and begin treatment immediately. In the advanced stages of Cushing’s, the bulging pituitary gland applies pressure to the brain causing compression which may be severe enough to manifest neurological dysfunction. At this point, disease is occurring, which is very difficult to overcome.
Traditionally, it was believed that Cushing’s was caused by tumors. However, as Janice Posnikoff, DVM, effectively describes in her article published in Horse Illustrated 2005, “Cushing’s has often been described as a benign tumor of the brain, but there is still debate whether it’s a tumor or hypertrophy, which is tissue enlargement as a result of increased work (similar to the way that muscles enlarge from exercise)...It’s unknown which comes first, hypertrophy or the tumor.”
What are the symptoms of Cushing's Syndrome?
Horses with Cushing’s Syndrome display a very consistent pathology.
- Poor hair coat: long guard hairs, wavy coat, lack of shedding, excessive sweating
- Cresty neck
- Abnormal deposits of fat (typically on the crest of the neck, shoulders, rump and sheath)
- Fluid collection directly above the eye (supraorbital fossas)
- Founder/chronic laminits
- Excessive thirst (polydipsia) and excessive urination (polyuria)
- Increased appetite without corresponding weight gain
- Swaybacked or pot-bellied appearance
- Loss of muscle mass and or topline tone
- Lethargy
- Sterility
- Respiratory disease, skin infections, food abscesses and mouth ulcers
- Depleted immune system
Neurological symptoms and ataxia may occur during final stages of disease
A misconception about Cushing’s disease is that affected horses are hypothyroid and fat. They’re not. We don’t know enough about the thyroid gland and its hormones, but currently it’s believed that the thyroid does not play a direct role in equine Cushing’s disease. Thyroid supplementation hasn’t been proven to help horses with Cushing’s.
Predisposition
While Cushing’s Syndrome can occur in horses of all ages or breeds, there have been discussions among veterinarians to suggest that it may be more common in Arabians and Morgans, as well as in some pony breeds. Cushing’s was often misdiagnosed as the normal aging process since it is seen in large numbers of elderly equines.
While most common in aging equines, Cushing’s Syndrome is being increasingly identified in younger horses due in part to the evolution of more sophisticated testing methodologies for the syndrome.
Show horses are definitely at a higher risk of developing Cushing’s. These days, it is not uncommon to see 10 year old show horses with this syndrome. The stress of high sugar/carbohydrate feed programs, training, hauling, vaccinating, ‘medicating’ for shows and stall confinement all contribute to a horse exhibiting early stages of Cushing’s symptoms.
Causes
Stress has the most staggering cumulative negative effect on the health of the horse. It is then turned into inflammation, which must be neutralized by the body.
It is critical to understand the body reacts to stress like a 911 operator. The pituitary gland receives the 911 call by recognizing the newly added stressor. It dispatches an ‘ambulance’ (hormones) to race to the adrenal glands. The adrenal glands then respond by releasing cortisol to diffuse the inflammation much in the way EMT’s triage a patient on the way to the hospital.
When the horse is bombarded daily with stressors (listed below), the pituitary gland becomes stressed out and feels like it cannot take a break. Eventually, it decides to stay at full alert at all times causing the adrenal glands to continue overproducing cortisol, which is the body’s way to fight inflammation.
Equine stress is commonly associated with:
- trailering
- training/showing
- sedation (dentals, castrations, surgery)
- injury
- changes in environment
The following less commonly recognized stressors for the horse are just as damaging:
- high sugar/carbohydrate feeds
- changes in diet
- vaccinations
- daily dewormers
- synthetic medications (ACTH, Regu-Mate®, steroids)
- stall confinement (see Ulcer article)
What are the negative side effects of these common stressors?
Unfortunately, when we feed complex carbohydrates and simple sugars to our horses it is not without negative side-effects. ALL grains, when digested, are processed and metabolized as sugar. Many horses are allergic to sugar in the diet. It is commonly manifested as hives, stocking up, mood swings, tying-up and body/back soreness. High sugar/grain content diets can adversely affect the functioning of the immune system. Horses with immune mediated diseases, such as Cushing’s, or that are immune compromised should never be fed grains especially in the form of sweet feeds. Refer to the Nutrition article for more information on proper feeding.
Vaccinations cause hyper-stimulation of the immune system and a corresponding inability of the body to attend to other diseases and stresses. Killed virus vaccinations also contain Thimerosal, a mercurial compound. Mercury poisoning damages the central nervous system, the immune system, kidney function and the endocrine system. If the immune system has been previously stimulated (by the last vaccine that hasn’t worn off yet) the next time you stimulate it, you can actually tear it down. Refer to the Vaccination article for more information on a holistic approach to vaccination protocol.
Daily dewormers contain small amounts of chemicals that are designed to prevent the growth of immature worms. This provokes the body to respond to the invasion of chemical and treat it as inflammation. This may not only lead to Cushing’s, but to developing a resistance to daily dewormers. Once parasites develop resistance to daily dewormers, the next step is resistance to paste dewormers. Refer to the Deworming article (coming soon) in the Digestive section for more information on a holistic approach to deworming.
Showing and competing horses presents a unique opportunity to administer synthetic drugs to alleviate moodiness, temperament changes or anxiety, which can negatively impact the health of the horse. The owner needs to recognize that long-term use of mare estrous (heat) cycle suppressants such as Regu-Mate® interfere with a mare’s (or in some cases, stallion’s) normal hormonal activity, which can lead to further consequences in the endocrine system. The over-use of synthetic ACTH (Adrenocorticotropic hormone) and Dexamethasone (glucocorticoid steroid) given to horses for calming in competition, is believed to create serious health issues. It is also common for synthetic steroids to be given to horses with skin and respiratory allergies, which can be harmful when used over a long periods of time.
How do I diagnosis Cushing's?
There are limited means to test for Cushing’s in horses and many of them are given to false positives/negatives. The most common test utilized to verify the diagnosis of Cushing’s is the Dexamethasone (Dex) Suppression Test or DST. In this test, the horse is given a dose of Dexamethasone following the extraction of a blood sample. After 24 hours, another sample is taken to compare the level of cortisol present in the blood. Cushing’s Syndrome horses will show less reduction in their cortisol levels than normal horses. This test is not typically recommended because Dexamethasone is a key trigger for laminitic (founder) episodes in Cushing’s horses.
To avoid administering Dexamethasone, other tests have been developed which do not produce the side effect of laminitis. One option to test levels of cortisol in the blood is the ACTH stimulation test. This test is run in the same fashion as the Dex tests, with 2 blood draws over a 2-8 hour time frame. In this method, the horse is given one unit of ACTH per kg of body weight. Affected horses will show a rise of four times the amount of cortisol in their blood versus the doubling of cortisol levels in a normal horse.
Research is bringing to light the potential inaccuracy of these tests, as there is a wide range of ‘normal’ hormone levels in horses. It is not uncommon for these tests to have false negatives when the Syndrome is just not advanced enough for the test to pick up on it. In addition, simply being off feed can throw hormone levels off by as much as 50 percent in some tests.
It is common practice to run a blood profile on suspected Cushing’s cases in order to verify that the horse has elevated insulin levels. Cushing’s syndrome corresponds in its symptomology to the newly discovered Syndrome X in humans and insulin resistance. For more information on these health concerns, please read the Metabolic article.
Some new research is being devoted to testing cortisol levels in saliva. Another test monitors the fluctuations of cortisol throughout a 24 hour period. In healthy horses, cortisol levels are higher in the morning and lower at night by more than 30 percent. If no change is detected, this is an indication that the pituitary gland is not shutting down.
A recommended course of action is to treat the symptoms from a holistic perspective. Instead of running tests that can be harmful or produce false negatives, proactively nutritionally support the pituitary gland with supplements and observe the presenting symptoms for signs of improvement.
What are the treatments?
It is important to begin treatment as soon as symptoms are identified. There are many treatment options available for Cushing’s Syndrome including synthetic drugs, nutrition and herbal supplements.
Drug therapy methods of treatment are listed below:
PERGOLIDE MESYLATE (Permax): Originally used to treat Parkinson’s disease in humans, this drug is a synthetic form of dopamine. It tells the pituitary to shut down production of cortisol, thereby improving related symptomology of the disease. While Pergolide Mesylate remains the primary recommendation for treatment of Cushing’s today, it has many negative side-effects. Loss of appetite and weight loss are common complaints from use of this drug. Lethargic attitude has been observed in some cases. Also of concern is a lack of information regarding the use of this drug in stallions or mares used for breeding. As such, it cannot safely be recommended in either instance. In addition, as Joyce Harman, DVM, points out, “As there is no cure for Cushing’s it must be noted that it is thought that eventually the condition will become resistant to this drug and greatly reduce the effectiveness of the treatment.”
CYPROHEPTADINE (Periactin): This medication is a serotonin blocker which is introduced at very small doses. With this medication, polyuria and polydipsia are monitored in order to ascertain if improvement is occurring. This drug was originally the treatment of choice for Cushing’s, but studies are now showing it to be less effective than Pergolide.
BROMOCRIPTINE MESYLATE (Parlodel): Less popular than the other two treatments above, this drug displays evidence of difficulty in absorption and negative side effects.
TRILOSTANE (Modrenal): A human drug used to treat Cushing’s in dogs and cats, some minimal experimentation with its use in equine cases of Cushing’s has been undertaken with favorable results. While further study will be required before the drug will be available in the US for use in equine Cushing’s treatment, the drug appears to have less negative side effects than Pergolide Mesylate or other traditional treatments. This medication works with the adrenal glands to slow the transition of progesterone to cortisol. More research is needed to reproduce positive findings and safe use in horses for FDA approval. Trilostane is available in the United Kingdom, and also to veterinarians here through special arrangement with drug compounding companies.
Dr. DePaolo recommends prevention of Cushing’s Syndrome as the best course of action. This condition is easily managed with nutrition prior to the display of pathology as well as after the onset of symptoms. Dr. DePaolo recommends nutritional support for the pituitary rather than artificially tricking the pituitary into a reduction of cortisol production. The benefits of this methodology are evident in the lack of secondary side effects and the safety of long term use.
Are there nutrition based methods of treatment?
DIET: Proper nutrition is critical in the management of Cushing’s Syndrome. Progression of the severity of symptoms is directly related to the feed program. As stated earlier in the ‘Causes’ section, high carbohydrate/sugar feeds create an inflammatory response in the body, and should be eliminated from the diet. Lush pasture grass and sweet feeds containing molasses are contraindicated for Cushing’s Syndrome horses.
The key feed alterations for Cushing’s horses are complete removal of all sugary grains and the soaking of hay. Soaking of the hay leeches natural sugars and is therefore much safer for Cushing’s and Insulin Resistant horse’s consumption. It is important to note that hays that are less green, leaning towards yellow, tend to have less sugar and more fiber. Higher fiber content hays help to stabilize blood sugar.
Better choices include those low on the glycemic index table presented in the Nutrition section of the Health Library. Included are: grass hays, grass pellets, rice bran. The Glycemic index of sweet feed is 123, as compared to rice bran which is 16. The lower the glycemic index the better when feeding Cushing’s syndrome horses. The lower the glycemic index rating for a feed, the more suitable it will be to maintain the health of Cushing’s syndrome or insulin resistant horses. Most horses are more than adequately maintained on grass hay and a mineral supplement. Treats such as cookies, carrots and apples should be fed sparingly as they are loaded with sugars.
To assist in the feeding of Cushing’s and insulin resistant horses, numerous companies have begun to produce “low-starch” grains -- it is important to check the ingredient list for molasses as some companies still include it as a binding agent. Horses should only be fed as much concentrated feed/’grain’ (ie. Grass pellets, rice bran) in their diet as needed to provide them with necessary vitamin and mineral supplements.
CHASTE TREE BERRY POWDER (vitex agnus castus): Chaste Tree Berry Powder nutritionally supports the normal functioning of the pituitary gland. With this herbal supplement, the pituitary is allowed to thrive and perform properly by naturally helping to maintain normal dopamine levels in the blood and supporting regulation of both the pituitary and adrenal glands. Accurate dopamine levels also normalize prolactin to balance hormones in the body. Chaste Tree Berry Powder has no known negative side effects and is safe for long term use.
According to an article written by Debra Johnson, Equine Cushing’s Disease, “In a study conducted in the UK, use of Vitex agnus castus caused ‘rapid and dramatic’ improvement.”
HARMONY: Harmony™ is a powerful all-natural supplement designed to promote a healthy metabolism and Endocrine System. These active ingredients combine many key nutraceuticals which help maintain normal blood sugar and hormone levels. Harmony™ is formulated to promote healthy body function in horses dealing with the negative side effects associated with Endocrine, Metabolic, and Cushing Syndromes, as well as Insulin Resistance and Hypothyroidism. To support these horses, Harmony™ is designed to aid in the maintenance of the thyroid and adrenal glands. It is recommended for more advanced stages of Cushing’s Syndrome and combating moody mare issues. Harmony™ has no known negative side effects and is safe for long term use.
Other methods of treatment are listed below:
Cushing’s horses that are not suffering from laminitis benefit greatly from regular exercise.
Affected horses who suffer from laminitis can be made comfortable with corrective shoeing and corresponding veterinary treatment for the pain and inflammation associated with this condition. Typically bute or banamine will be recommended to reduce inflammation and reduce discomfort. Acupuncture is also a viable treatment method for pain relief and healing. In severe cases, intravenous treatment with DMSO may be required.
Cushing’s is slowly progressive and often goes unrecognized in the early stages. It is important to understand this syndrome is managed, not cured. When caught early, treatment is very successful in reducing clinical signs and allowing affected horses to live almost normal lives. For those horses in advanced stages of the disease, treatment still offers improved quality of life and longevity. Overall, horse owners shouldn’t fear Cushing’s Syndrome, but must have a healthy respect for it and become educated about prevention.
This information is for educational purposes only and should not be considered as Dr. DePaolo diagnosing your horse’s health. DePaolo Equine Concepts, Inc. recommends that you consult your regular veterinarian regarding specific health concerns.
Tips for helping the Cushing's horse:
- Learn and recognize symptoms
- Avoid stressing the horse
- Eliminate vaccinations until horse is healthy
- Eliminate unnecessary synthetic medications and daily dewormer
- Follow proper nutrition protocol
Feed low glycemic index feeds:
- Rice bran
- Grass pellets
- Flax
- Beet pulp
Avoid high sugar feeds:
- Sweet feeds/treats
- Oats
- Corn
- Barley
- Wheat
- Rye
Do not feed high glycemic additives:
- Corn oil
- Molasses
- Apple sauce
Provide pituitary nutritional support:
- Chaste Tree Berry Powder
- Harmony™
- Provide exercise
- Proper trimming/shoeing