Diagnosis and management of thyroid disorders and thyroid hormone supplementation in adult horses and foals.

Equine thyroid disorders pose a diagnostic challenge in clinical practice because of the effects of nonthyroidal factors on the hypothalamic-pituitary-thyroid axis, and the horse's ability to tolerate wide fluctuations in thyroid hormone concentrations and survive without a thyroid gland. While benign thyroid tumours are common in older horses, other disorders like primary hypothyroidism or hyperthyroidism in adult horses and congenital hypothyroidism in foals are rare. There is a common misunderstanding regarding hypothyroidism in adult horses, especially when associated with the clinical profile of obesity, lethargy, and poor performance observed in dogs and humans. Low blood thyroid hormone concentrations are often detected in horses as a secondary response to metabolic and disease states, including with the nonthyroidal illness syndrome; however, it is important to note that low thyroid hormone concentrations in these cases do not necessarily indicate hypothyroidism. Assessing equine thyroid function involves measuring thyroid hormone concentrations, including total and free fractions of thyroxine (T4) and triiodothyronine (T3); however, interpreting these results can be challenging due to the pulsatile secretion of thyroid hormones and the many factors that can affect their concentrations. Dynamic testing, such as the thyrotropin-releasing hormone stimulation test, can help assess the thyroid gland response to stimulation. Although true hypothyroidism is extremely rare, thyroid hormone supplementation is commonly used in equine practice to help manage obesity and poor performance. This review focuses on thyroid gland pathophysiology in adult horses and foals, interpretation of blood thyroid hormone concentrations, and evaluation of horses with thyroid disorders. It also discusses the use of T4 supplementation in equine practice.

Glucose and Insulin Responses to an Intravenous Glucose Load in Thoroughbred and Paso Fino Horses.

Certain breeds of horses may be genetically predisposed to developing insulin dysregulation, which is a risk factor for development of endocrinopathic laminitis in horses. This study was performed to test the hypotheses that Paso Fino horses exhibit evidence of insulin dysregulation compared with Thoroughbred horses and that obesity exaggerates the insulin dysregulation. Intravenous glucose tolerance tests were performed in 14 moderate-weight Thoroughbreds, 12 moderate-weight Paso Finos, and 12 overweight Paso Finos. Moderate Paso Finos had greater baseline serum insulin concentrations, area under the insulin concentration curve, peak insulin, insulin-to-glucose ratio, area under the insulin to glucose curve, and modified glucose-to-insulin ratio compared with moderate Thoroughbreds. The reciprocal inverse square of basal insulin (RISQI) and glucose-to-insulin ratio were significantly lower in moderate Paso Finos compared with moderate Thoroughbreds. Overweight Paso Finos had greater baseline insulin concentrations, area under the insulin concentration curve, time to peak insulin, baseline plasma glucose concentration, insulin-to-glucose ratio, and area under the insulin to glucose curve compared with moderate Paso Finos. The RISQI and glucose-to-insulin ratio were significantly lower in overweight Paso Finos compared with moderate Paso Finos. In conclusion, moderate-weight Paso Finos had higher baseline serum insulin concentrations and an excessive hyperinsulinemic response to an intravenous glucose load when compared with moderate-weight Thoroughbreds. Overweight Paso Finos had even greater baseline insulin concentrations and hyperinsulinemic responses to glucose compared with moderate Paso Finos, as well as greater baseline plasma glucose concentrations. Paso Finos exhibit insulin dysregulation compared with Thoroughbreds.

Thyroid Hormone and Thyrotropin Concentrations and Responses to Thyrotropin-Stimulating Hormone in Horses with PPID Compared with Age-Matched Normal Horses.

Glucocorticoids are known to exert inhibitory action on the hypothalamic-pituitary-thyroid axis. With recent evidence that free plasma cortisol and urinary excretion of cortisol metabolites may be increased in horses with pituitary pars intermedia dysfunction (PPID), it is important to further examine thyroid function in horses with PPID. To test the hypothesis that serum thyrotropin (TSH) concentrations are decreased in horses with PPID, baseline serum thyroid hormone and TSH concentrations, and responses to TSH-releasing hormone (TRH), were compared between 12 horses diagnosed as having PPID and 14 age-matched normal horses. Horses with PPID had resting serum concentrations of free thyroxine by equilibrium dialysis (fT4D) and TSH that were significantly lower than serum concentrations of fT4D and TSH in age-matched normal horses. Serum concentrations of total T4 and total and free triiodothyronine (T3) were also lower in horses with PPID compared with normal horses, but the differences did not reach statistical significance. Thyroid hormone and TSH responses to TRH administration were not different between horses with PPID and normal horses. In conclusion, serum fT4D concentrations are decreased in horses with PPID without an appropriate increase in serum TSH concentrations. Normal serum thyroid hormone and TSH concentration responses to exogenous TRH administration support the theory that increased glucocorticoid activity in horses with PPID may exert prolonged tonic suppression, but not complete inhibition, of TRH and subsequent TSH release, similar to what has been observed in other species.

Serum Thyroid Hormone and Thyrotropin Concentrations in Adult Horses as They Age.

With more horses remaining active longer in life, it is important to characterize changes that occur normally with aging, so that these can be differentiated from development of disease. The objective of the study was to test the hypotheses that geriatric horses have lower circulating concentrations of thyroid hormones and/or higher serum thyrotropin (TSH) concentrations compared to younger horses. Serum thyroid hormone and TSH concentrations from 71 normal, healthy horses that had participated in prior research projects were analyzed for effects of age, sex, and season when samples were obtained. All samples had been assayed in the same previously validated radioimmunoassays. There were no differences in serum concentrations of thyroid hormones or TSH by sex or season. Serum total thyroxine (T4) was greater in 3- to 6-year-old horses compared to all other age groups and was negatively correlated with age. There were no differences among age groups for free T4 and total and free tri-iodothyronine (T3). Serum TSH concentration was significantly greater in old horses (≥15 or ≥20 years) compared to young (3-10 years) and intermediate (11-14 years) age groups. Serum TSH was positively correlated with age. There were no significant differences in thyroid hormone responses to thyrotropin releasing hormone (TRH) among young, intermediate, or old horses. However, the TSH response to TRH was significantly different in both groups of older horses compared to intermediate and young horses. Serum total thyroxine concentrations decrease and serum TSH concentrations increase in horses as they age, with no changes in free T4 or T3.

Extreme lymphocytosis with myelomonocytic morphology in a horse with diffuse large B-cell lymphoma.

An 11-year-old, 443-kg Haflinger mare was presented to the North Carolina State University Veterinary Teaching Hospital with a 2-week history of lethargy and a 3-day duration of anorexia, pyrexia, tachycardia, and ventral edema. Severe pitting edema, peripheral lymphadenopathy, and a caudal abdominal mass were noted on physical examination. An extreme leukocytosis (154.3 × 103 /µL) and microscopic hematologic findings suggestive of myelomonocytic leukemia were observed. Serum protein electrophoresis revealed a monoclonal gammopathy and urine protein electrophoresis revealed a monoclonal light chain proteinuria. Necropsy and histopathology confirmed widespread neoplastic infiltration in many organs with a heterogenous population of cells; there was no apparent evidence of bone marrow involvement. Immunohistochemistry confirmed presence of a majority of B cells with a limited antigen expression, admixed with a lower number of T cells. Molecular clonality analysis of IgH2, IgH3, and kappa-deleting element (KDE, B cell) on whole blood and KDE on infiltrated tissues revealed clonal rearrangements, and the KDE intron clones that amplified in blood and in infiltrated tissue were identical. In contrast, the clonality analysis of T-cell receptor γ revealed no clonality on blood cells and infiltrated tissues. In conjunction with the histopathologic changes, the lesion was interpreted to be composed of neoplastic B cells with a reactive T-cell population. Polymerase chain reaction testing for equine herpes virus 5 was negative. The final diagnosis was diffuse large B-cell lymphoma with a marked hematogenous component.

Disorders of the equine thyroid gland.

Regulatory control of the thyroid gland in horses is similar to other species. Clinical signs of hypothyroidism in adult horses are minimal. Several drugs and physiologic and pathophysiological states can cause circulating thyroid hormone concentrations to be low without actual pathology of the thyroid gland. Thus, nonthyroidal factors must be ruled out before a diagnosis of hypothyroidism can be made. Thyroid hormone supplementation seems to be well tolerated, even in euthyroid horses. Neonatal foals have very high circulating thyroid hormone concentrations, and deficiencies result in significant clinical signs. Unlike in adults, two syndromes of hypothyroidism are well described in foals.

Cardiovascular effects of acute pulmonary obstruction in horses with recurrent airway obstruction.

BACKGROUND: Recurrent airway obstruction (RAO) is common in horses. Although pulmonary artery (PA) pressure increases during RAO, cardiac function in horses with RAO has received limited attention. HYPOTHESIS: The purpose of this study was to noninvasively determine the cardiovascular effects of acute pulmonary obstruction (APO) in horses with RAO and their reversibility. ANIMALS: Five geldings with RAO, inducible by exposure to moldy hay, were studied. METHODS: Pulmonary mechanics, echocardiography, serum troponin I concentrations, arterial blood gases, and hematocrit were obtained before and after 7 days of APO. Heart rate, PA diameter and flow characteristics, right and left ventricular luminal dimensions and wall thicknesses, global cardiac performance, and evidence of myocardial damage were evaluated. Pulmonary mechanics and echocardiography were reevaluated during remission. RESULTS: [corrected] Severe, transient APO did not induce chronic cor pulmonale in horses, because cardiac anatomy and function were normal between episodes. An acute episode of APO produced anatomical and functional cardiac changes in both the right and left heart (including increased PA diameter, abnormal septal motion, and decreased left ventricular diameter and estimated stroke volume), possibly because of the development of pulmonary hypertension, without apparent myocardial damage. The decrease in stroke volume was offset by the increase in heart rate. CONCLUSIONS AND CLINICAL IMPORTANCE: With APO of 7 days' duration, cardiovascular abnormalities and the functional airway changes that produce them are reversible when the offending allergens are removed.

Measurement of free thyroxine concentration in horses by equilibrium dialysis.

The purpose of the study reported here was to validate measurement of free thyroxine (fT4) concentration in equine serum by equilibrium dialysis (fT4D), and to compare values with fT4 concentration measured directly and with total T4 (TT4) concentration. The fT4D, fT4, and TT4 concentrations were measured over a range of values in euthyroid horses and horses made hypothyroid by administration of propylthiouracil (PTU). Concentrations of fT4D (<1.8-83 pmol/L) were consistently higher than those of fT4 (<1-40 pmol/L). There was a significant (P < .001) regression of fT4D on fT4 in 503 samples from normal horses (y = 2.086x - 0.430). In baseline samples from 71 healthy euthyroid horses, fT4 concentration ranged from 6-21 pmol/L (median, 11 pmol/L; 95% confidence interval [CI]10.5-11.8 pmol/L), and fT4D concentration ranged from 7-47 pmol/L (median, 22 pmol/L; 95% CI 20.9-25.1 pmol/L). Free T4D, fT4, and TT4 concentrations were also measured in 34 ill horses. Horses consuming PTU and ill horses had significantly (P < .05) lower serum concentration of TT4, fT4, and fT4D than did clinically normal, healthy horses. If serum samples from ill horses were further subdivided into samples from horses that lived and samples from horses that died, fT4D concentration was not significantly different in ill horses that lived, compared with that in healthy horses, whereas fT4 concentration was still significantly decreased in ill horses that died (P < 0.001). We conclude that measurement of fT4 concentration by equilibrium dialysis is a valid technique in the horse, and its use may provide improved ability to distinguish nonthyroidal illness syndrome from hypothyroidism in that species.

Thyroid function in mature horses ingesting endophyte-infected fescue seed.

OBJECTIVE: To determine whether ingestion of fescue seed infected with the endophyte Neotyphodium coenophialum would alter thyroid function in adult horses. DESIGN: Original study. ANIMALS: 4 adult mares that were not pregnant and 6 adult geldings. PROCEDURE: Thyrotropin releasing hormone stimulation tests were performed while horses received a standard diet and after infected seed (2.3 kg/d [5 lb/d]) had been fed for 1 and 2 months. Serum prolactin concentrations were measured to verify endophyte absorption. RESULTS: Serum prolactin concentrations indicated that at least 8 of 10 horses absorbed the endophyte. Baseline concentrations of thyroid stimulating hormone, total and free triiodothyronine, and total and free thyroxine and the change in hormone concentrations in response to administration of thyrotropin releasing hormone (1 mg, i.v.) were not altered by ingestion of endophyte-infected fescue seed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that ingestion of fescue seed infected with the endophytic fungus N. coenophialum for 2 months has little effect on thyroid function in adult horses that are not pregnant.

Congestive heart failure in horses: 14 cases (1984-2001).

OBJECTIVE: To identify clinical signs, underlying cardiac conditions, echocardiographic findings, and prognosis for horses with congestive heart failure. DESIGN: Retrospective study. ANIMALS: 14 horses. PROCEDURE: Signalment; history; clinical signs; clinicopathologic, echocardiographic, and radiographic findings; treatment; and outcome were determined by reviewing medical records. RESULTS: All 14 horses were examined because of a heart murmur; tachycardia was identified in all 14. Twelve horses had echocardiographic evidence of enlargement of 1 or more chambers of the heart. Other common clinical findings included jugular distention or pulsation, crackles, cough, tachypnea, and ventral edema. Nine horses had signs consistent with heart failure for > 6 days. Underlying causes for heart failure included congenital defects, traumatic vascular rupture, pericarditis, pulmonary hypertension secondary to heaves, and valvular dysplasia. Seven horses were euthanatized after diagnosis of heart failure; 5 were discharged but were euthanatized or died of complications of heart disease within 1 year after discharge. The remaining 2 horses were discharged but lost to follow-up. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that congestive heart failure is rare in horses. A loud heart murmur accompanied by either jugular distention or pulsation, tachycardia, respiratory abnormalities (crackles, cough, tachypnea), and ventral edema were the most common clinical signs. Echocardiography was useful in determining the underlying cause in affected horses. The long-term prognosis for horses with congestive heart failure was grave.

Thyroid-stimulating hormone in adult euthyroid and hypothyroid horses.

The purpose of this study was to validate a thyroid-stimulating hormone (TSH) assay in a model of equine hypothyroidism. Thyrotropin-releasing hormone (TRH) stimulation tests were performed in 12 healthy adult mares and geldings, aged 4 to greater than 20 years. before and during administration of the antithyroid drug propylthiouracil (PTU) for 6 weeks. Serum concentrations of equine TSH, total and free thyroxine (T4), and total and free triiodothyronine (T3) were measured. Before PTU administration, mean +/- standard deviation baseline concentrations of TSH were 0.40 +/- 0.29 ng/mL. TSH increased in response to TRH, reaching a peak concentration of 0.78 +/- 0.28 ng/mL at 45 minutes. Total and free T4 increased from 12.9 +/- 5.6 nmol/L and 12.2 +/- 3.5 pmol/L to 36.8 +/- 11.4 nmol/L and 23.1 +/- 5.9 pmol/L, respectively, peaking at 4-6 hours. Total and free T3 increased from 0.99 +/- 0.51 nmol/L and 2.07 +/- 1.14 pmol/L to 2.23 +/- 0.60 nmol/l and 5.78 +/- 1.94 pmol/L, respectively, peaking at 2-4 hours. Weekly measurements of baseline TSH and thyroid hormones during PTU administration showed that total and free T, concentrations fell abruptly and remained low throughout PTU administration. Total and free T4 concentrations did not decrease dramatically until weeks 5 and 4 of PTU administration, respectively. A steady increase in TSH concentration occurred throughout PTU administration, with TSH becoming markedly increased by weeks 5 and 6 (1.46 +/- 0.94 ng/mL at 6 weeks). During weeks 5 and 6 of PTU administration, TSH response to TRH was exaggerated, and thyroid hormone response was blunted. Results of this study show that measurement of equine TSH in conjunction with thyroid hormone measurement differentiated normal and hypothyroid horses in this model of equine hypothyroidism.