Endocrinopathic laminitis in the horse

Abstract

Protracted laminitis and the resultant stress often results in prolonged, elevated cortisol secretion and this may contribute to the persistence and refractoriness of laminitis. Cushing’s disease is a condition in which increased secretion of pituitary pars intermedia-derived pro-opiomelanocortin (POMC) peptides leads to perpetually enhanced adrenal secretion of cortisol (hyperadrenocorticism), the physiological glucocorticoid (GC) in the equine species. The vasoconstrictive responses of equine digital arteries to catecholamines is potentiated by GCs leading to interference with hoof lamellar perfusion. The level of the steroid-transforming enzyme, 11β-hydroxysteroid dehydrogenase type 1 is sometimes elevated in hoof lamellar tissues during laminitis as a result of locally high cortisol concentrations within hoof lamellae. Obesity has been shown to be a significant risk factor for the development of laminitis. Obesity-associated laminitis may be similar to the metabolic syndrome (MS) in obese humans. Development of MS is a risk factor in humans for stroke and atherosclerosis and there may be a similar risk for laminitis in horses. GCs cause insulin resistance (IR) by inhibiting the action of insulin thus promoting the availability of glucose for cells in the CNS and other cells that do not depend on insulin for glucose uptake. GCs may impair lamellar perfusion by direct action on vascular smooth muscle and indirectly by causing IR. Equine hoof lamellar keratinocytes appear to have an exceptionally high glucose requirement and maintenance of the lamellar may rely on glucose delivery to and uptake by these keratinocytes. Chronic IR, characterized by hyperglycemia and hyperinsulinemia, subjects cells that are not dependent on insulin for glucose uptake to relatively high glucose levels over time. Glucotoxic endotheliopathy is characterized by increased production of endothelin-1 and reduced release of NO by endothelial cells and these constricting factors may impair lamellar perfusion and risk of laminitis. Horse owners and veterinarians should recognize that obesity is associated with multiple endocrinological changes that might predispose to laminitis. Feeding high glycemic index rations during long periods of physical inactivity promotes the development of obesity. A diagnosis of metabolic syndrome (MS) should be considered in horses with abnormal body fat distribution and laminitis. Identification of IR represents the most useful clinical approach to diagnosing MS in horses and rations for horses with MS should have a low glycemic index. Diagnosis of pituitary pars intermedia dysfunction (PPID) in teenage (and younger) horses before the development of the “classic” signs of hirsutism and weight loss is being reported more commonly using the e-ACTH criterion. Therefore, veterinary diagnosticians must be careful to differentiate whether obese teenage horses might be affected with either or both IR and PPID before the appearance of the more “classic” Cushing’s phenotype is evident. The extent to which these two endocrinological disturbances are related deserves further investigation.