Effects of long-term oral administration of levothyroxine sodium on serum thyroid hormone concentrations, clinicopathologic variables, and echocardiographic measurements in healthy adult horses

OBJECTIVE: To determine the effects of long-term oral levothyroxine sodium (L-T(4)) administration on serum thyroid hormone concentrations, thyroid gland function, clinicopathologic variables, and echocardiographic examination measurements in adult euthyroid horses. ANIMALS: 6 healthy adult mares. PROCEDURES: Horses received L-T(4) (48 mg/d) orally for 48 weeks. Every 4 weeks, physical examinations were performed; blood samples were collected for CBC, plasma biochemical analyses, and assessments of serum total triiodothyronine (tT(3)) and thyroxine (tT(4)) concentrations. Plasma creatine kinase MB activity and cardiac troponin I concentration were also measured. Echocardiographic examinations were performed before and at 16, 32, and 48 weeks during the treatment period. RESULTS: During the treatment period, mean body weight decreased significantly; heart rate varied significantly, but the pattern of variation was not consistent. Significant time effects were detected for certain clinicopathologic variables, but mean values remained within reference ranges. Cardiac troponin I was only detectable in 8 of 24 plasma samples (concentration range, 0.01 to 0.03 ng/mL). Serum creatine kinase MB activity did not change significantly over time. Compared with the pretreatment value, 5.4-, 4.0-, and 3.7-fold increases in mean serum tT(4) concentrations were detected at 16, 32, and 48 weeks, respectively. Some cardiac measurements changed significantly over time, but mean values remained within published reference ranges. Mean fractional shortening was lower than the pretreatment mean value at 16 and 32 weeks. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, long-term oral administration of 48 mg of L-T(4)/d significantly increased serum tT(4) concentrations and did not appear to adversely affect health.     

Short-term influence of prednisone and phenobarbital on thyroid function in euthyroid dogs.

The short-term effects of prednisone and phenobarbital on serum total thyroxine (tT4), free thyroxine (fT4), and thyroid stimulating hormone (TSH) were evaluated in euthyroid dogs. Twenty-six beagles were randomly divided into 3 groups receiving, respectively, a placebo, prednisone (1.2 to 2 mg/kg body weight, per os, every 12 hours for 3 weeks), or phenobarbital (1.8 to 3 mg/kg body weight for 1 week, then 2.7 to 4.5 mg/kg body weight, per os, every 12 hours for 2 weeks). Blood samples taken over a 6-week period were assayed for serum tT4, fT4, and TSH. Phenobarbital therapy in our study did not affect serum tT4, fT4, or TSH concentrations. Prednisone therapy, however, significantly decreased serum tT4 and fT4, but did not affect serum TSH concentrations.     

Thyroid hormone concentrations differ between donkeys and horses

Reasons for performing study: Reference intervals for thyroid hormones (TH) concentrations have not been previously established for donkeys, leading to potential misdiagnosis of thyroid disease. Objectives: To determine the normal values of TH in healthy adult donkeys and compare them to TH values from healthy adult horses. Methods: Thirty‐eight healthy Andalusian donkeys and 19 healthy Andalusian horses from 2 different farms were used. Donkeys were divided into 3 age groups: <5, 5–10 and >11 years and into 2 gender groups. Serum concentrations of fT3, tT3, rT3, fT4 and tT4 were quantified by radioimmunoassay. All blood samples were collected the same day in the morning. None of the animals had received any treatment for 30 days prior to sampling or had any history of disease. Both farms were in close proximity and under similar management. Differences between groups were determined using a one‐way ANOVA analysis followed by Fisher's LSD test. P<0.05 was considered significant. Results: Serum TH concentrations were higher in donkeys than in horses (P<0.01). Donkeys <5 years had higher serum rT3, fT4 and tT4 concentrations than donkeys >5 years (P<0.05). Furthermore, older donkeys (>11 years) had lower serum fT3 and tT3 concentrations than younger donkeys’ groups (<5 and 5–10 years, P<0.05). TH concentrations were not different between genders (fT3: P = 0.06; tT3: P = 0.08; rT3: P = 0.15; fT4: P = 0.89; and tT4: P = 0.19). Conclusions: Thyroid hormone concentrations are different between healthy adult donkeys and horses. Potential relevance: Establishing species‐specific TH reference ranges is important when evaluating clinicopathologic data in equids in order to avoid the misdiagnosis of thyroid gland dysfunction. Further studies to elucidate the physiological mechanisms leading to these differences are warranted.     

Evaluation of the effects of clomipramine on canine thyroid function tests

To evaluate the effect of long-term clomipramine administration on the hypothalamic-pituitary-thyroid axis in healthy dogs, 14 healthy adult dogs were enrolled in a prospective study. Clomipramine (3 mg/kg PO q12h) was administered to all dogs beginning on day 0, and continued for 112 days. Serum total thyroxine (T4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3; rT3), and thyroid-stimulating hormone (TSH) were measured on days 0, 7, 28, 42, 56, and 112. Thyrotropin-releasing hormone (TRH) response tests were performed concurrently. Significant decreases were noted in serum T4, f4, and rT3 concentrations beginning on day 28 through the end of the study period. The lowest mean (+/-SEM) concentrations of T4 (26 +/- 1.2 to 17 +/- 0.5 nmol/L) and rT3 (1.21 +/- 0.13 to 0.83 +/- 0.08 nmol/L) occurred at day 112, whereas the lowest mean fT4 (29 +/- 2.4 to 18 +/- 1.7 pmol/L) was found on day 56 of clomipramine treatment. The effect of treatment over time on serum T3 concentration also was significant, but the deviation in T3 from baseline was variable. No significant effect of clomipramine treatment was noted on either pre- or post-TRH TSH concentrations. The 35 and 38% decreases in serum T4 and fT4 concentrations, respectively, during clomipramine administration may lead to a misdiagnosis of hypothyroidism. Although no evidence of hypothyroidism was noted in this study population, subclinical hypothyroidism may have occurred. A longer duration of treatment might further suppress thyroid function, and concurrent illness or other drug administration might exacerbate clomipramine's effects.     

Clinical Evaluation of a Novel Liquid Formulation of L-Thyroxine for Once Daily Treatment of Dogs with Hypothyroidism

Background: A liquid solution of levothyroxine (L-T4) is available for treatment of canine hypothyroidism.
Hypothesis: Once daily oral administration of a liquid L-T4 solution is effective and safe for controlling hypothyroidism in dogs.
Animals: Thirty-five dogs with naturally occurring hypothyroidism.
Methods: Dogs received L-T4 solution PO once daily at a starting dosage of 20 μg/kg body weight (BW). The dose was adjusted every 4 weeks, based on clinical signs and peak serum total T4 (tT4) concentrations. Target peak serum tT4 and thyroid stimulating hormone (TSH) concentrations, 4–6 hours posttreatment, were 35–95 nmol/L and < 0.68 ng/mL, respectively. Dogs were followed for up to 22 weeks after establishment of the maintenance dose.
Results: Clinical signs of hypothyroidism improved or resolved in 91% of dogs after 4 weeks of L-T4 treatment at 20 μg/kg once daily. The maintenance dose was established in 76, 94, and 100% of dogs after 4, 8, and 12 weeks of treatment, respectively. This was 20 μg L-T4/kg BW for 79% of the dogs, 30 μg/kg BW for 15%, and 10–15 μg/kg BW in the remaining 6%, once daily. Thereafter, median peak tT4 and TSH concentrations were 51 nmol/L and 0.18 ng/mL, respectively, and remained stable during the 22-week follow-up; clinical signs did not recur.
Conclusions and Clinical Importance: All of the hypothyroid dogs had rapid clinical and hormonal responses to supplementation with the PO-administered L-T4 solution. The starting dosage of 20 μg L-T4/kg BW once daily was suitable for 79% of dogs.     

Effect of levothyroxine administration on hemostatic analytes in Doberman Pinschers with von Willebrand disease

Levothyroxine administration has been suggested to be an effective treatment for canine von Willebrand disease (vWd), but evidence supporting this treatment is lacking. Effects of levothyroxine administration were evaluated in 8 euthyroid Doberman Pinschers with plasma von Willebrand factor (vWf) concentrations < 15%, characteristic of type 1 vWd. Levothyroxine (0.04 mg/kg PO q12h) and placebo were administered for 30 days in a 2-period, 2-treatment, double-blinded, crossover design with a 30-day washout period between treatments. Buccal mucosal bleeding time (BMBT), plasma vWf concentration (vWf: Ag), vWf collagen binding activity (vWf:CBA), factor VIII coagulant activity (FVIII:C), and serum concentrations of total thyroxine (T4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured on days 0, 2, and 30 of each treatment period. The 8 dogs (1 male, 7 females) had markedly low plasma vWf:Ag (mean, 8.9%; reference range, 70-180%) and vWf:CBA (mean, 11.1%; reference range, >70%). Response to placebo versus levothyroxine treatment was not significantly different between groups at day 0, 2, or 30 for BMBT, vWf:Ag, vWf:CBA, and FVIII:C. Serum T4, fT4, and T3 concentrations were significantly higher and serum TSH significantly lower in the levothyroxine-treated group than in the placebo group at days 2 and 30. Administration of levothyroxine at 0.04 mg/kg caused laboratory evidence of hyperthyroidism but did not affect plasma FVIII:C and vWf:Ag concentrations or vWf-dependent collagen binding and BMBT. The results of this study failed to identify a direct action of levothyroxine supplementation on plasma vWf concentration or activity in euthyroid Doberman Pinschers with vWd.     

Use of recombinant human thyroid-stimulating hormone for thyrotropin-stimulation testing of euthyroid cats

OBJECTIVE: To evaluate response of euthyroid cats to administration of recombinant human thyroid-stimulating hormone (rhTSH). ANIMALS: 7 healthy cats. PROCEDURE: Each cat received each of 5 doses of rhTSH (0, 0.025, 0.050, 0.100, and 0.200 mg), IV, at 1-week intervals. Serum concentration of total thyroxine (TT4) and free thyroxine (fT4) was measured immediately before each injection (time 0) and 2, 4, 6, and 8 hours after administration of each dose. RESULTS: Overall TT4 response did not differ significantly among cats when administered doses were > or = 0.025 mg. Serum TT4 concentrations peaked 6 to 8 hours after administration for all doses > or = 0.025 mg. For all doses > or = 0.025 mg, mean +/- SEM TT4 concentration at 0, 6, and 8 hours was 33.9 +/- 1.7, 101.8 +/- 5.9, and 101.5 +/- 5.7 nmol/L, respectively. For all doses > or = 0.025 mg, mean fT4 concentration at 0, 6, and 8 hours was 38.7 +/- 2.9, 104.5 +/- 7.6, and 100.4 +/- 8.0 pmol/L, respectively. At 8 hours, the fT4 response to 0.025 and 0.050 mg was less than the response to 0.100 and 0.200 mg. Adverse reactions after rhTSH administration were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: The TSH stimulation test can be performed in cats by IV administration of 0.025 to 0.200 mg of rhTSH and measurement of serum TT4 concentrations at time of injection and 6 or 8 hours later. Clinical validation of the TSH stimulation test would facilitate development of additional tests of thyroid gland function, such as a TSH assay.     

Effects of long-term oral administration of levothyroxine sodium on glucose dynamics in healthy adult horses

OBJECTIVE: To determine the effects of long-term oral administration of levothyroxine sodium (L-T(4)) on glucose dynamics in adult euthyroid horses. ANIMALS: 6 healthy adult mares. PROCEDURES: Horses received L-T(4) (48 mg/d) orally for 48 weeks. Frequently sampled IV glucose tolerance test procedures were performed on 3 occasions (24-hour intervals) before and at 16, 32, and 48 weeks during the treatment period. Data were assessed via minimal model analysis. The repeatability of measurements was evaluated. RESULTS: During treatment, body weight decreased significantly from the pretreatment value; mean +/- SD weight was 49 +/- 14 kg, 43 +/- 7 kg, and 25 +/- 18 kg less than the pretreatment value at weeks 16, 32, and 48, respectively. Compared with pretreatment findings, 1.8-, 2.4-, and 1.9-fold increases in mean insulin sensitivity (SI) were detected at weeks 16, 32, and 48, respectively; SI was negatively correlated with body weight (r = -0.42; P < 0.001). During treatment, glucose effectiveness increased and the acute insulin response to glucose decreased. Overall mean within-horse coefficients of variation were 5% and 29% for plasma glucose and serum insulin concentrations, respectively, and 33%, 26%, and 23% for SI, glucose effectiveness, and the acute insulin response to glucose, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Long-term administration of L-T(4) was associated with weight loss and increased SI in adult euthyroid horses, although other factors may have confounded results. Levothyroxine sodium may be useful for the treatment of obesity and insulin resistance in horses, but further studies are required.     

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.     

Thyroid function testing in Greyhounds.

OBJECTIVE: To evaluate thyroid function in healthy Greyhounds, compared with healthy non-Greyhound pet dogs, and to establish appropriate reference range values for Greyhounds. ANIMALS: 98 clinically normal Greyhounds and 19 clinically normal non-Greyhounds. PROCEDURES: Greyhounds were in 2 groups as follows: those receiving testosterone for estrus suppression (T-group Greyhounds) and those not receiving estrus suppressive medication (NT-group Greyhounds). Serum thyroxine (T4) and free thyroxine (fT4) concentrations were determined before and after administration of thyroid-stimulating hormone (TSH) and thyroid-releasing hormone (TRH). Basal serum canine thyroid stimulating hormone (cTSH) concentrations were determined on available stored sera. RESULTS: Basal serum T4 and fT4 concentrations were significantly lower in Greyhounds than in non-Greyhounds. Serum T4 concentrations after TSH and TRH administration were significantly lower in Greyhounds than in non-Greyhounds. Serum fT4 concentrations after TSH and TRH administration were significantly lower in NT-group than T-group Greyhounds and non-Greyhounds. Mean cTSH concentrations were not different between Greyhounds and non-Greyhounds. CONCLUSIONS AND CLINICAL RELEVANCE: Previously established canine reference range values for basal serum T4 and fT4 may not be appropriate for use in Greyhounds. Greyhound-specific reference range values for basal serum T4 and fT4 concentrations should be applied when evaluating thyroid function in Greyhounds. Basal cTSH concentrations in Greyhounds are similar to non-Greyhound pet dogs.     

Endotoxn-induced nonthyroidal illness in dogs

OBJECTIVE: To determine the effects of endotoxin administration on thyroid function test results and serum tumor necrosis factor-alpha (TNF-alpha) activity in healthy dogs. ANIMALS: 6 healthy adult male dogs. PROCEDURES: Serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3), free T4 (fT4), and endogenous canine thyroid stimulating hormone (TSH), and TNF-alpha activity were measured before (day-1; baseline), during (days 0 to 3), and after (days 4 to 24) IV administration of endotoxin every 12 hours for 84 hours. RESULTS: Compared with baseline values, serum T3 concentration decreased significantly, whereas rT3 concentration increased significantly 8 hours after initial endotoxin administration. Serum T4 concentration decreased significantly at 8 and 12 hours after initiating endotoxin administration. Serum T4 concentration returned to reference range limits, then decreased significantly on days 6 to 12 and 16 to 20. Serum fT4 concentration increased significantly at 12, 24, and 48 hours after cessation of endotoxin treatment, compared with baseline values. Serum rT3 concentration returned to reference range, then decreased significantly days 5 and 7 after stopping endotoxin treatment. Serum TNF-alpha activity was significantly increased only 4 hours after initial endotoxin treatment, compared with baseline activity. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxin administration modeled alterations in thyroid function test results found in dogs with spontaneous nonthyroidal illness syndrome. A decrease in serum T4 andT3 concentrations and increase in serum rT3 concentration indicate impaired secretion and metabolism of thyroid hormones. The persistent decrease in serum T4 concentration indicates that caution should be used in interpreting serum T4 concentrations after resolution of an illness in dogs.     

Effects of oral administration of levothyroxine sodium on concentrations of plasma lipids, concentration and composition of very-low-density lipoproteins, and glucose dynamics in healthy adult mares

OBJECTIVE: To evaluate glucose and lipid metabolism in healthy adult horses administered levothyroxine sodium (L-T4). ANIMALS: 12 healthy adult mares. PROCEDURE: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provide between 7 AM and 8 AM in the morning grain meal for 2 weeks. Four additional horses remained untreated. Serum concentrations of nonesterified fatty acids, triglyceride (TG), total cholesterol (TC), and very-low-density lipoprotein (VLDL) were measured and composition of VLDL examined in samples obtained between 8 AM and 9 AM at weeks 0, 2, 4, 6, and 8. Glucose dynamics were assessed by use of a combined IV glucose-insulin tolerance test (IVGITT) conducted before and at the end of the 8-week treatment period. Data for each combined IVGITT were interpreted by use of the minimal model. RESULTS: Plasma TG, TC, and VLDL concentrations significantly decreased over time in treated horses. At the completion of the 8-week treatment period, mean plasma VLDL concentration was 46% of the mean value for week 0 in treated horses. Insulin sensitivity significantly increased (> 2-fold) in treated horses, but glucose effectiveness and net insulin response were not affected. Levothyroxine sodium significantly increased the rate of insulin disposal. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-T4 decreases blood lipid concentrations, improves insulin sensitivity, and increases insulin disposal in horses. Levothyroxine sodium may have potential as a treatment for horses with reduced insulin sensitivity.     

Serum concentrations of thyroxine, 3,5,3'-triiodothyronine, thyrotropin, and prolactin in dogs before and after thyrotropin-releasing hormone administration

Serum concentrations of thyrotropin (TSH), prolactin, thyroxine, and 3,5,3'-triiodothyronine in 15 euthyroid dogs and 5 thyroidectomized and propylthiouracil-treated dogs after thyrotropin-releasing hormone (TRH) administration were measured. Although thyroidectomized and propylthiouracil-treated dogs had higher (P less than 0.01) base-line concentrations of TSH in serum than did euthyroid dogs, concentrations of TSH after TRH administration varied at 7.5, 15, and 30 minutes with 14 of 45 samples obtained from healthy dogs having lower TSH concentrations than before TRH challenge. Similarly, concentrations of 3,5,3'-triiodothyronine in the serum of euthyroid dogs 4 hours after TRH administration were similar (P less than 0.05) to concentrations before TRH challenge. Although the mean concentration of thyroxine in serum was elevated (P less than 0.05) 4 hours after administration of TRH to euthyroid animals, as compared with base-line levels, the individual response was variable with concentrations not changing or decreasing in 4 dogs. Therefore, the TRH challenge test as performed in the current investigation was of limited value in evaluating canine pituitary gland function. Although mean concentrations of TSH in serum were higher (P less than 0.05) in euthyroid dogs after TRH administration, the response was too variable among individual animals for accurate evaluation of pituitary gland function. Concentrations of prolactin in the sera of dogs after TRH administration, confirmed previous reports that exogenously administered TRH results in prolactin release from the canine pituitary and indicated that the TRH used was biologically potent.     

Serum thyroid hormone concentrations and thyrotropin responsiveness in dogs with generalized dermatologic disease.

Fifty-eight dogs with generalized dermatologic disease that had not been given glucocorticoids systemically or topically within 6 weeks of entering the study were evaluated for thyroid function by use of the thyrotropin-response test. Dogs were classified as euthyroid or hypothyroid on the basis of test results and response to thyroid hormone replacement therapy. Baseline serum thyroxine (T4), free T4 (fT4), and triiodothyronine (T3) concentrations were evaluated in the 58 dogs. Serum T4, fT4, and T3 concentrations were evaluated in 200 healthy dogs to establish normal values. Hormone concentrations were considered low if they were less than the mean -2 SD of the values for control dogs. Specificity of T4 and fT4 concentrations was 100% in predicting hypothyroidism; none of the euthyroid dogs with generalized skin disease had baseline serum T4 or fT4 concentration in the low range. Sensitivity was better for fT4 (89%) than for T4 (44%) concentration. Significant difference was not observed in serum T4 and fT4 concentrations between euthyroid dogs with generalized skin disease and healthy control dogs without skin disease. Serum T3 concentration was not accurate in predicting thyroid function; most of the euthyroid and hypothyroid dogs with skin disease had serum T3 concentration within the normal range.     

Comparison of serum-free thyroxine concentrations determined by standard equilibrium dialysis, modified equilibrium dialysis, and 5 radioimmunoassays in dogs

Measurement of serum-free thyroxine (fT4) concentration provides a more accurate assessment of thyroid gland function than serum thyroxine (T4) or 3,5,3'-triiodothyronine (T3). Techniques for measuring serum fT4 concentration include standard equilibrium dialysis (SED), radioimmunoassay (RIA), and a combination of both (modified equilibrium dialysis [MED]). This study compared results of serum fT4 measurements by means of SED, MED, and 5 RIAs in 30 healthy dogs, 10 dogs with hypothyroidism, and 31 euthyroid dogs with concurrent illness for which hypothyroidism was a diagnostic consideration. Serum fT4 concentrations were comparable when determined by the SED and MED techniques, and mean serum fT4 concentrations were significantly (P < .01) lower in dogs with hypothyroidism than in healthy dogs and euthyroid dogs with concurrent illness. Significant (P < .05) differences in fT4 concentrations were identified among the 5 RIAs and among the RIAs and MED and SED. Serum fT4 concentrations were consistently lower when fT4 was determined by the RIAs, compared with either equilibrium dialysis technique. Serum fT4 concentrations were significantly lower (P < .01) in dogs with hypothyroidism than in healthy dogs for all RIAs; were significantly lower (P < .05) in dogs with hypothyroidism than in euthyroid dogs with concurrent illness for 4 RIAs; and were significantly lower (P < .01) in euthyroid dogs with concurrent illness than in healthy dogs for 4 RIAs. RIAs had the highest number of low serum fT4 concentrations in euthyroid dogs with concurrent illness. This study documented differences in test results among fT4 assays, emphasizing the importance of maintaining consistency in the assay used to measure serum fT4 concentrations in the clinical or research setting.     

Effect of oral administration of prednisolone on thyroid function in dogs

To determine the effect of oral administration of prednisolone on thyroid function, 12 healthy Beagles were given 1.1 mg of prednisolone/kg of body weight every 12 hours for 22 days after 8 days of diagnostic testing of the dogs before treatment with prednisolone. Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) response tests were performed before treatment (days 1 and 8 of the study) and during treatment (days 21 and 28 of the study). Blood samples were collected daily at 8 AM and 2 and 8 PM to rule out normal daily hormone fluctuations as the cause of a potential decrease in serum triiodothyronine (T3), thyroxine (T4), and free T4 (fT4) concentrations. Serum T3, T4, and fT4 concentrations before treatment and 1 day and 21 days after the first prednisolone dose were compared by analyses of variance. Post-TSH and -TRH serum T3 and T4 concentrations before and during treatment were compared, using the Student t test for paired data. Oral administration of prednisolone significantly (P less than 0.005) decreased serum T3, T4, and fT4 concentrations in the 8 AM and 2 and 8 PM samples obtained 1 day and 21 days after the first prednisolone dose. Serum T4 and fT4 concentrations in 8 AM and 2 PM samples were significantly (P less than 0.05) lower 21 days after the first prednisolone dose than they were at 1 day after the first dose. Before treatment, serum T4 concentration in the 2 PM samples was significantly (P less than 0.05) higher than serum T4 concentration in 8 AM and 8 PM samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

Equine thyroid function assessment with the thyrotropin-releasing hormone response test

The effect of thyrotropin-releasing hormone (TRH) on equine thyroid function was determined by quantifying serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) before and after TRH administration. Thyrotropin-releasing hormone was administered IV to adult horses (n = 5) and ponies (n = 6) at a dose of 1 mg or 0.5 mg, respectively. Serum T4 and T3 concentrations were determined before and 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after TRH administration. Serum T4 increased from a basal concentration of 24.4 +/- 8.7 ng/ml (mean +/- SD) to a maximum value of 48.2 +/- 10.2 by 4 hours after TRH administration. Serum T3 increased from a basal concentration of 0.44 +/- 0.18 ng/ml to a maximum value of 1.31 +/- 0.37 ng/ml by 2 hours after TRH administration. Seemingly, TRH increases serum concentrations of T4 and T3 and may be useful as a test of equine hypophysis-thyroid function.     

Thyrotropin-releasing hormone stimulation testing in healthy dogs

Serum triiodothyronine (T3) and thyroxine (T4) concentrations were determined after IV administration of 200 micrograms of thyrotropin-releasing hormone (TRH) to 10 healthy euthyroid dogs. Significant (P less than 0.05) changes were not found in the T3 concentration throughout an 8-hour sampling interval. All dogs had a significant increase (P less than 0.05) in the T4 concentration at 4, 5, 6, 7, and 8 hours after TRH administration. The largest increase in the serum T4 concentration occurred 4 hours after TRH injection. From 4 to 8 hours after TRH administration, the mean increase above basal T4 concentrations was 13.9 +/- 5.4 ng/ml.     

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.     

Assessment of serum thyroid hormone concentrations in lambs with selenium deficiency myopathy

OBJECTIVE: To assess changes in serum concentrations of thyroid hormones associated with selenium deficiency myopathy in lambs. ANIMALS: 35 lambs with selenium deficiency myopathy and 30 healthy lambs. PROCEDURES: Blood samples were collected via jugular venipuncture from lambs with selenium deficiency myopathy and healthy lambs. Activities of markers of selenium deficiency myopathy (erythrocyte glutathione peroxidase [GSH-Px] and plasma creatine kinase [CK]) and serum thyroid-stimulating hormone (TSH) and total thyroxine (tT(4)) and total triiodothyronine (tT(3)) concentrations were assessed; values in affected lambs were compared with those in healthy lambs. Correlations of erythrocyte GSH-Px and plasma CK activities with serum concentrations of TSH, tT(4), and tT(3) were investigated, and the tT(3):tT(4) concentration ratio was evaluated. RESULTS: Compared with findings in healthy lambs, erythrocyte GSH-Px activity, serum tT(3) concentration, and tT(3):tT(4) concentration ratio were significantly decreased and serum concentrations of tT(4) and TSH and the activity of plasma CK were significantly increased in affected lambs. Analysis revealed a significant negative correlation in the affected group between erythrocyte GSH-Px activity and each of the following: plasma CK activity (r = -0.443), serum TSH concentration (r = -0.599), serum tT(4) concentration (r = -0.577), and serum tT(3) concentration (r = -0.621). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that notable changes in circulating amounts of thyroid hormones develop in association with selenium deficiency in lambs. Such alterations in thyroid hormone metabolism may be involved in the high incidence of disorders, such as stillbirths and neonatal deaths, in selenium-deficient flocks.