Endocrinologic laminitis (Proceedings)

The term endocrinologic laminitis was coined by Dr. Phil Johnson and colleagues in 2004, and is meant to describe laminitis that arises from hormonal abnormalities – primarily insulin resistance – rather than inflammatory or mechanical causes. It encompasses pasture-associated laminitis, and is thus the most common manifestation of laminitis seen in horses and ponies. The two most common conditions that predispose to endocrinologic laminitis are equine metabolic syndrome (EMS) and pituitary pars intermediate dysfunction (PPID, Equine Cushing's Disease).

Defining a subset of the horses with laminitis as suffering from “endocrinopathic” laminitis is a double edged sword. It helps practitioners remember that abnormal glucose and insulin metabolism is the central disorder in many cases of laminitis, and that insulin resistance must be addressed as part of the treatment of the disease. The term has the potential to mislead, however, as it suggests that endocrinopathic laminitis has a separate pathogenesis from the cases that occur secondary to inflammatory disease. Advances in the field happen all the time, but the depth of our current understanding of the inciting events of laminitis does not permit us to make that claim.

First and foremost, an underlying endocrinologic abnormality should always be suspected when a horse suddenly develops laminitis without an obvious precipitating factor. This includes the pony that develops “Labor Day Laminitis” in the fall or the animal that has trouble during times of lush pasture growth. Studies of pasture-associated laminitis reveal a marked over-representation of ponies when compared to horses. 

There appears to be genetic predisposition for pasture-associated laminitis within breeds. A large study of closely observed ponies found that development of laminitis ran within lines with many related ponies developing the disease while unrelated animals were spared. Affected lines of ponies were found to be insulin-resistant prior to the onset of laminitis, linking these two disorders.

The mechanism by which high insulin concentrations produce laminitis is not well understood. Experimentally, inducing hyperinsulinemia for prolonged periods of time will result in the development of laminitis in horses and ponies without any other predisposing factors. Insulin has various effects on the endothelial cells, and the most current theory is that insulin-mediated endothelial damage in the sensitive laminae of the hoof may predispose to laminar inflammation. In addition, many insulin resistant horses are obese, and increased adipose mass is associated with an increase in pro-inflammatory cytokines and other factors that can also produce endothelial cell damage.

Glucocorticoid-associated laminitis

The experimental evidence linking glucocorticoid administration to acute laminitis is lacking. Despite this, many equine practitioners can recall a patient who suffered a bout of laminitis shortly after glucocorticoid administration, and there is ample anecdotal evidence linking exogenous corticosteroids with laminitis. Glucocorticoids are potent insulin antagonists. Injection with 0.05 mg/kg triamcinolone I.M. resulted in hyperglycemia and hyperinsulinemia for over 48 hours. This potential association should not prevent a practitioner from administering corticosteroids in horses that require their treatment, such as a horse with purpura hemorrhagica. It does behoove clinicians to use this class of drugs sparingly and only when indicated.

PPID associated laminitis

PPID is a common disease of aged horses, with over 15% of the aged population suffering from the disease. Not all horses with PPID are insulin-resistant, but those that are have a high risk of developing laminitis. In one study, horses with PPID that presented with high serum insulin conditions when diagnosed were much more likely to develop laminitis and die within 2 years of diagnosis than horses that had normal or only mildly elevated insulin concentrations at diagnosis.

Ponies are over-represented in population surveys testing for PPID, and they may develop the signs at an earlier age than other horses. Although the presence of hirsutism makes identification of advanced cases of PPID quite easy, many horses have pituitary dysfunction for years before they develop an abnormal hair coat. Laminitis may be the first clinical sign noted. In one study, 70% of horses with unexplained laminitis had evidence of PPID as determined by elevated αMSH concentrations.

There is a certain subset of horses with PPID that appear to have adrenal gland involvement and are much more likely to experience severe laminitis and frequent flare-ups. The recently-described HCG response test may be helpful in identifying these animals. In brief, serum cortisol concentrations are measured before and then 5, 15, and 30 minutes after administration of 10,000 IU (one bottle) of HCG. A spike in cortisol concentrations indicates an abnormal response of the adrenal gland.

The 3β-hydroxysteroid dehydrogenase inhibitor (Trilostane®) may be of benefit in these horses. In one abstract, the clinical signs of laminitis were improved in 13 of 16 horses with PPID after trilostane administration. It is an extremely expensive drug, however, and even the compounded form is out of reach for many horse owners.

Management of Endocrinologic Laminitis

Horses with PPID should be treated with pergolide at a dose sufficient to bring endogenous ACTH concentrations and/or evocative test results back into normal ranges. In many instances, a low dose of pergolide results in some improvement in clinical appearance, but does not yield a decrease in ACTH concentrations. These horses remain at risk for laminitis.

Horses with insulin resistance can be extremely challenging to manage. Often a combination of pharmacologic, dietary, and management changes are needed.  [See the discussions of Equine Metabolic Syndrome in these proceedings for a more in-depth discussion of EMS]. Losing weight will improve insulin sensitivity. If the horse is over-conditioned, the diet should be restricted so that weight is lost until the animal has a condition score of no more than 6 out of 9.

Treatment of laminitis

Once laminitis develops, excellent ongoing hoof care is imperative. Corrective trimming based on the radiographic appearance of the feet is essential. The feet should be trimmed in a way that allows easy breakover and broad-based support of the foot. There seem to be as many opinions as to the most correct way to trim and shoe a horse with chronic laminitis as there are veterinarians and farriers. A good rule of thumb is to “let pain be your guide.” A trimming and shoeing strategy that allows a horse to be comfortable is the ultimate goal. What works for one horse may cause the next one more pain.

Trimming and shoeing should be avoided immediately after an acute flare-up when the foot is still painful. Access to the sole should be preserved as subsolar abscesses are extremely common, particularly in horses with PPID. Many times, what is initially perceived to be a flare-up of laminitis is in fact the development of another painful foot condition. It is important for the practitioner to carefully examine the sole for bruising and other defects when evaluating a lame horse with laminitis which suddenly experiences much more pain.

Forage

Pasture-associated laminitis is difficult to study due to the ever changing nutritional content of pasture grasses. Plant constituent concentrations change rapidly in response to weather conditions, rainfall, plant species and maturity of the plant. Local conditions have a larger bearing on plant make-up than species, which makes planting “safe” pasture grasses impossible. The relatively rapid changes in plant carbohydrate content can make grazing especially dangerous to very high risk horses. Some horses tolerate grazing muzzles, which allows them to spend time on pasture while ingesting very limited amounts of forage. In some instances, restricting all pasture access is needed before laminitis flare-ups can be eliminated.

There are two times in the year when pastures tend to have high non-structural carbohydrate concentrations: the spring and autumn. In both seasons there tends to be ample rain fall, high daytime temperatures, and low or freezing nighttime temperatures. Normally, plants use the sun's energy during the day to form nonstructural carbohydrates and other constituents. At night, these are turned into the structural elements needed for plant growth and development. When night temperatures are low, the enzymatic processes that convert non-structural to structural carbohydrates are inhibited and nonstructural carbohydrate levels increase.

The nonstructural carbohydrate concentration of hay is largely dependent on the make-up of the plants when they were cut. Hay analysis is needed to determine the nutrient breakdown. Study after study has demonstrated that one can not use the hay's plant composition, color, or feel to determine non-structural carbohydrate concentrations. Hay that is considered excellent quality due to a bright green color and lack of stems may in fact contain few nutrients and be safe to feed to an insulin-resistant horse. Meanwhile, a second bale that would easily be mistaken for straw may have extremely high carbohydrate levels.

There are many independent laboratories that will provide hay analysis at relatively low cost. As forage is the basis of a feeding program, it is extremely important to know what a high-risk horse is consuming when it eats hay. Soaking hay in water for 30 to 60 minutes will remove some of the soluble carbohydrate and can be a technique used to lower the non-structural carbohydrate concentration. Unfortunately, the amount of soluble carbohydrate removed is not constant, and is often a relatively small percent of the total. Also, care must be taken to ensure that the hay does not become moldy before it is fed, as this can lead to respiratory problems.

There are numerous supplements and dietary constituents that have been shown to improve insulin sensitivity in man or other species. These include various herbs, chromium, magnesium, and cinnamon. To date, none of these products have improved insulin sensitivity in equine studies.

The most important factors when feeding an animal with laminitis and insulin resistance is to feed a diet that is balanced for macro- and micronutrients and has the calories needed to maintain a normal weight. The amount of nonstructural carbohydrate should be monitored, composing no more than 10-12% of the total diet. Many feed companies have responded to the increased awareness of the problems associated with feeding typical high carbohydrate diets to horses by marketing low-starch feeds.

When evaluating these, one should look for feeds that are specifically designed for insulin-resistant horses with low overall caloric density. Many of the low-starch feeds marketed for horses with such muscle problems replace carbohydrate calories with fat. The insulin-resistant horse does not need the caloric density fat provides.

Exercise

It can be extremely difficult for insulin-resistant horses to reap the benefits from exercise as their lameness prevents much more than hand walking. Researchers have shown that regular exercise, even mild exercise such as 30 minutes of trotting per day, improves insulin sensitivity in the muscles. In addition, exercise decreases the circulating concentrations of tumor necrosis factor and other pro-inflammatory cytokines that can be over -xpressed in insulin-resistant, obese animals.

The positive effects of exercise do not persist after cessation of activity. Thus, regular exercise will benefit a horse that is sound enough to partake in a daily routine, but will not have a lasting or residual benefit if a bout of laminitis prevents continued activity.  There have been no studies published on the beneficial effects of non-weight bearing exercise in laminitic horses such as swimming or exercising on a treadmill in water. Presumably a lame horse would enjoy the positive benefits of exercise without pain or further damage to the hoof.