Exercise intolerance, endocrine disorders and chronic weight loss

Common clinical complaints in adult equine patients include exercise intolerance, chronic weight loss and suspect endocrine disorders. Determining the underlying cause for these conditions requires formulation of a complete list of Differential and the appropriate diagnostic procedures. Some diagnostic procedures may require the expertise from a referral veterinary hospital; however, the following review is structured to provide insight on the causes of these conditions and the recommended diagnostics for the ambulatory practitioner.

This pony mare presents hirsutism, secondary to PPID. This condition is chronic and progressive; therefore, the goal of therapy is to achieve a satisfactory quality of life for the equine patient.

Exercise intolerance is defined as a disinclination to move quickly in the absence of any apparent physical lameness, incoordination or respiratory distress. Determination of the underlying cause requires a thorough history and extensive physical exam. The list of Differential should be subdivided into major organ systems. These include the cardiovascular, respiratory and metabolic systems.

• Cardiovascular evaluation

Evaluation of the cardiovascular system begins with careful, bilateral auscultation of the cardiac sounds. Care should be taken to listen for at least 60 seconds while calculating the heart rate and listening for any arrhythmias. In addition, the arterial pulse (facial or transverse facial artery) should be palpated simultaneously to determine if the arterial pulses are synchronous with every heart beat. Cardiac murmurs should be described by intensity (Grade 1 to 5), point of maximum intensity (PMI) and timing (systolic versus diastolic). Auscultation of abnormal heart sounds and/or rhythm provides adequate indication for performing an electrocardiogram (ECG) and two-dimensional echocardiography. Second-degree AV block is the most common arrhythmia in

normal

horses — especially fit athletic horses. The ECG findings include QRS complexes preceded by a P wave with normal to near-normal PR interval, but there are occasional P waves not followed by a QRS complex. Less common, advanced second-degree AV block typically causes significant exercise intolerance and potentially collapse. The ECG findings are similar to "normal" second-degree AV block except for frequent and multiple unconducted P waves. The most common arrhythmia in horses associated with clinical signs is atrial fibrillation. Auscultation of heart sounds reveal an irregular heart rhythm that may be normal or accelerated in rate. Both advanced second-degree AV block and atrial fibrillation require immediate medical attention.

Differentials for exercise intolerance associated with the upper respiratory tract include laryngeal hemiplegia (left), displacement of the soft palate, aryepiglottic entrapment and obstructive upper airway lesions, including ethmoid hematomas, cysts and sinusitis.

In addition to arrhythmias, valvular insufficiency as detected by the auscultation of a murmur may result in signs of exercise intolerance. Additional clinical signs include distended jugular pulses, tachycardia, distal-limb edema and generalized poor doing. Mitral valve insufficiency is the most common cause of cardiac failure in adult horses and results in a systolic murmur that is loudest on the left side of the horse. In contrast, aortic insufficiency is the most common cause of heart murmurs in horses and typically it is not associated with clinical signs of cardiac disease. Aortic valve regurgitation often presents as a diastolic murmur that is musical and loudest on the left or right side of the horse. Irrespective, the detection of a cardiac murmur is sufficient indication to perform two-dimensional echocardiography.

• Respiratory check

Following auscultation of the cardiac sounds, careful inspection of the respiratory tract should be included in assessment of an equine patient with exercise intolerance. Careful evaluation of respiratory sounds and effort should be compared between inspiration and expiration. The respiratory system should be divided into the upper and lower respiratory tracts. Differential for exercise intolerance associated with the upper respiratory tract include laryngeal hemiplegia, displacement of the soft palate, aryepiglottic entrapment and obstructive upper airway lesions, including ethmoid hematomas, cysts and sinusitis. Evaluation of the upper respiratory tract requires endoscopy of the middle and dorsal nasal meatus, naso-pharynx, guttural pouches, larynx and proximal trachea. In addition, skull radio-graphs often are helpful in discerning the extent of obstructive lesions. Complete endoscopic assessment of the naso-pharynx and larynx might require treadmill analysis in order to determine if intermittent displacement of the soft palate is occurring and to determine the degree of laryngeal hemiplegia.

Differential for exercise intolerance associated with the lower respiratory tract include broncho-pneumonia, interstitial pneumonia, pleural pneumonia, inflammatory airway disease, heaves, exercise-induced pulmonary hemorrhage and tracheal collapse. Initial evaluation of the lower airway requires a thorough history, physical exam and a re-breathing exam. Airway sounds in adult horses at rest normally are difficult to discern, hence a re-breathing exam should be performed to increase the respiratory rate and inspiratory effort. Sick horses often will cough and might not tolerate the re-breathing exam for more than 30-45 seconds. If an infectious process is suspected, then a CBC, trans-thoracic ultrasound and thoracic radiographs are indicated.

Treating a horse with chronic weight loss requires the determination of whether the horse is eating or is anorexic. If the horse is not eating, then a thorough systemic assessment of the horse is indicated to determine the cause of inappetence. In addition, the farm management and feed quality should be documented.

Two diagnostic procedures available to sample fluid from within the pulmonary tree include a bronchio-alveolar lavage (BAL) and trans-tracheal wash (TTW). Both procedures can be performed in the field, however the indications to perform these exams are distinct. The sample of fluid collected from a BAL is representative of a large area of the pulmonary tree, in particular the dorsal lung fields. The fluid is not sterile and is not valuable for culture and sensitivity purposes. However, the cell population is very helpful for diagnosing heaves, exercise-induced pulmonary hemorrhage and inflammatory airway disease. In contrast, the sterile fluid collected via a TTW represents the cranial-ventral — and to some degree caudal-ventral — lung fields and is ideal for culture and sensitivity when diagnosing infectious causes of pulmonary disease. Often, both a BAL and TTW are performed, but the TTW must be performed before the BAL for the culture results to be diagnostic. When diagnosing pleuropneumonia, a TTW is indicated along with culture of the pleural fluid. Often more than one pathogen is present, and the appropriate antibiotic coverage is dependent on the culture results of the TTW and pleural fluid.

• Metabolism

In addition to exercise intolerance caused by cardiovascular and respiratory tract abnormalities, the condition may be associated with carbohydrate metabolism irregularities.

An increasing percentage of horses have been diagnosed with various degrees of genetically predisposed carbo-hydrate intolerance. These include polysaccharide storage myopathy (PSSM) in Quarter Horses, equine polysaccharide storage myopathy (EPSM) in Draft Breed horses, and idiopathic chronic exertional rhabdomyolysis in Standardbred and Arabian horses. These conditions are characterized by repeated episodes of exertional rhabdomyolysis that can be induced by minimal exercise. Clinical signs associated with these conditions include a repeated history of stiff gait, anxiety and reluctance to move.

These signs are associated with elevations in muscle enzymes. The predominant characteristic of these diseases is mild to severe accumulation of abnormal polysaccharide within the myoplasm, and the cause appears to be related to glucose metabolism. In PSSM, significant accumulation of abnormal polysaccharide might not be visible until 3 years of age in some horses. Muscle biopsies from these horses demonstrate greater total muscle glycogen content compared to normal horses. More importantly, horses with PSSM appear to store glycogen in the form of straight chains of glucose rather than the branched configuration of glucose molecules that make up normal glycogen.

The abnormal accumulation of glucose molecules in straight chains reduces the sites for the enzymes responsible for breaking down glycogen to operate. Therefore, when there is a physiologic demand for glucose via glycogen breakdown, horses with PSSM experience episodes of rhabdomyolysis. Diagnosis is based on the presence of abnormal polysaccharide on a periodic acid-schiff stained muscle biopsy. In addition, an exercise tolerance test can be a useful diagnostic tool. Effected horses commonly experience a doubling or more of baseline CK activity after 15 minutes of trotting on a lunge line. Treatment involves nutritional management. The diet should be modified to provide adequate calories for the level of activity of the horse but should limit the intake of carbohydrate. Diets containing increased percentage of crude fat rather than grains have proven effective in combination with quality forage and mineral/vitamin supplements.

Equine polysaccharide storage myopathy (EPSM) in Draft Breed horses is similar to PSSM, however some clinical variations exist. EPSM is associated with a second clinical syndrome characterized by progressive poor performance, shivers, progressive muscle wasting, muscle weakness and recumbency. Similar to PSSM, diagnosis of EPSM is based on clinical signs and demonstrating abnormal glycogen accumulation in muscle biopsies. In addition, treatment of EPSM involves increasing fat intake and reducing carbohydrate intake. Idiopathic chronic exertional rhabdomyolysis in Standardbred and Arabian horses is similar to EPSM and PSSM with regards to clinical history. However, some horses do not respond to dietary changes, and muscle biopsies are not always consistent.

• Endocrine disorders

Endocrine disorders in adult horses include thyroid dysfunction, pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome. In general, endocrine disorders are rare in horses, yet the most common is PPID, otherwise known as Cushing's disease. This endocrine condition in the horse is attributed to hyperplasia or adenoma formation of the pituitary pars intermedia. This results in excessive production of the hormones pro-opiomelanocortin (POMC) and adrenocorticotropic hormone (ACTH) by the pars intermedia. The mean age of effected horses is 18 to 23 years, and clinical signs include hirsutism, weight loss, poor performance, polyuria, polydipsia (PU/PD) and chronic recurrent laminitis. As the condition progresses, it is common to note deposition of fat along the crest of the neck, over the tail head and in the supraorbital areas. In addition, delayed wound healing and an increased incidence of secondary infections are reported in equids with PPID. The diagnosis of PPID is based on the documentation of clinical signs, a complete serum chemistry analysis and the dexa-methasone suppression test (DTS). Additional supportive data may include serum insulin and ACTH levels. Measurement of plasma cortisol levels alone is not a valid diagnostic test because of its diurnal rhythm and the substantial interindividual variation in cortisol levels among healthy and sick horses. Although the DST is considered the "gold standard" endocrine test for diagnosis of PPID, administration of the test should be considered carefully, especially in patients with a history of laminitis. In brief, the overnight DST includes measuring cortisol in the afternoon, followed by administration of dexa-methasone (40 ug/kg, IM) and subsequently measuring cortisol levels 17 to 19 hours later. Normal suppression should be tenfold. Treatment of PPID is a combination of management changes and medical treatment. Management includes dietary modifications to monitor caloric intake, routine body clipping, routine dental prophylaxis and frequent farrier visits. In addition, serotonin antagonist (cyproheptadine) and dopamine agonist (pergolide) are medications that have been used to treat horses with PPID. This condition is chronic and progressive; therefore, the goal of therapy is to achieve a satisfactory quality of life for the equine patient.

Equine metabolic syndrome is an endocrine disorder that has been described in obese horses suffering from recurrent laminitis. This condition has also been termed "peripheral cushing-oid syndrome" and is not well described. A state of insulin-resistance or refractoriness is believed to develop secondary to excessive fat deposition and the overproduction of endogenous glucocorticoids (cortisol). Horses with metabolic syndrome are typically obese and range in age between 8 and 18 years. An increased incidence of this condition has been reported in Paso Fino and pony breeds. Clinical signs include development of a "cresty neck" and rump due to excess accumulation of subcutaneous fat. Often, the horse presents for recurrent laminitis and is described as an overweight "easy keeper" for which losing weight is challenging. Hyperinsulinemia in the presence of normal or slightly elevated glucose levels in the fasted animal is suggestive of equine metabolic syndrome. This condition must be differentiated from PPID.

By far, the most over-diagnosed endocrine condition in adult horses is hypo-thyroidism; however, true hypothyroidism is exceptionally rare in adult horses. A combination of clinical signs including obesity, laminitis, infertility and low circulating levels of T3 and T4 typically result in the erroneous diagnosis. The majority of equine patients misdiagnosed are euthyroid, and the underlying cause of the clinical signs and low thyroid hormones usually does not involve the thyroid gland. True hypothyroid equids suffer from cold intolerance, coarse hair coat, weight loss, hirsutism and exercise intolerance. Equine-specific TSH (thyroid stimulating hormone) assays and TSH- or TRH-stimulation tests are required to diagnose hypothyroidism in horses accurately. Unfortunately, these tests are not easily accessible or commonly performed. Thyroid hormone supplementation should be reserved only for well-documented cases of hypo-thyroidism.

• Chronic weight loss

Chronic weight loss is a common complaint that often presents as a diagnostic challenge to the practitioner. Working up a case of chronic weight loss requires a consistent and systematic approach. The first most important question to ask is whether the horse is eating or is anorexic (see Table 1,). If the horse is not eating, then a thorough systemic assessment of the horse is indicated to determine the cause of inappetence. In addition, the farm management and feed quality should be documented. If the initial assessment has determined that the horse is consuming a sufficient quantity of a quality feed yet losing weight or not gaining weight, decreased nutrient utilization, increased metabolic demand or organ failure should be considered. Decreased nutrient utilization may result from conditions effecting the gastric mucosa, small intestine and large intestine. These include diseases, such as gastric ulcers, infiltrative bowel disease and regional colitis. Gastric ulceration includes the non-glandular and glandular portion of the equine stomach. Typically, weight loss is associated with a decrease in feed intake due to the pain associated with eating. However, an additional component may involve decreased digestive capability due to ulceration of the glandular stomach. Diagnosis of gastric ulceration is dependent on gastroscopy.

Table 1: Cause, protocols for diagnosing chronic weight loss

A broader disease category that is associated with decreased nutrient utilization is infiltrative bowel disease. This includes plasmacytic-lymphocytic enteritis, eosinophilic enteritis, granulocytic enteritis and intestinal lymphosarcoma. A less common disease due to the advent of ivermectin is Strongylus vulgaris migration through the cranial mesentery vasculature resulting in micro-thrombi formation. Although the etiologies vary, all of these conditions result in nutrient malabsorption and chronic weight loss. Diagnosis is dependent on evaluating absorptive ability via a xylose absorption test followed by intestinal biopsy. Occasionally, trans-abdominal ultrasound reveals thickened loops of small intestine suggestive of an infiltrative process. These conditions carry a guarded prognosis and may respond to steroid administration. Nutritional care requires highly digestible feed such as complete feeds or senior feeds with a source of quality forage.

The most common example of regional colitis is right dorsal colitis (RDC). The inflammation of the colon is initiated by the use of non-steroidal anti-inflammatory drugs (NSAIDs), especially phenylbutazone, which results in significant protein loss through the compromised bowel wall. Although these horses have normally functioning small intestine, the protein loss through the large colon wall results in a catabolic state. Patients typically present with a history of orthopedic ailment that was addressed with NSAIDs followed by a period of reduced appetite, ± colic, and ventral edema. Serum albumin levels are reduced resulting in reduced oncotic pressure, and trans-abdominal ultrasound may reveal a thickened right dorsal colon. Diagnosis is based on ruling out all other causes of hypoproteinemia and a consistent history. Treatment involves serum transfusions and diet modification that reduce forage quantity to allow the colon time to heal.

Michael B. Porter earned his master's in science, PhD and DVM from the University of Florida. He completed a residency in large animal internal medicine at the University of Florida in July, 2004, and he currently is a clinical assistant professor at its School of Veterinary Medicine. He is director of the new Mobile Equine Diagnostic Service (MEDS).