Effect of storage of reconstituted recombinant human thyroid-stimulating hormone (rhTSH) on thyroid-stimulating hormone (TSH) response testing in euthyroid dogs

Bovine thyrotropin (bTSH) stimulation testing has long been considered the gold standard for diagnosis of canine hypothyroidism. Unfortunately, bTSH is no longer commercially available. Recently, the use of recombinant human thyrotropin (rhTSH) to perform thyroid-stimulating hormone (TSH) stimulation testing in dogs was described. The cost of an rhTSH vial (1.1 mg) limits the practical use of this product. The study reported here was performed to determine the effects of storing rhTSH on the post-TSH increase of serum total (TT4) and free (FT4) thyroxine concentrations during TSH stimulation testing in 12 euthyroid Beagles in a crossover trial. Three TSH tests with recombinant human thyrotropin (rhTSH; 91.5 microg IV) were performed on each dog during 3 different periods: 1 with freshly reconstituted rhTSH (fresh); 1 with rhTSH, reconstituted and stored at 4 degrees C for 4 weeks (refrigerated); and 1 with rhTSH, reconstituted and frozen at -20 degrees C for 8 weeks (frozen). Blood samples for determination of TT4 and FT4 concentrations were collected before and 4 and 6 hours after rhTSH administration. There was no significant difference in TT4 or FT4 concentration after stimulation with fresh, refrigerated, and frozen rhTSH. Furthermore, there was no significant difference between TT4 or FT4 serum concentration observed 4 and 6 hours after rhTSH administration. In conclusion, reconstituted rhTSH can be stored at 4 degrees C for 4 weeks and at -20 degrees C for 8 weeks without loss of biological activity, allowing clinicians to perform more TSH response tests per vial.     

Effects of administration of a low dose of frozen thyrotropin on serum total thyroxine concentrations in clinically normal dogs.

Thyroid function was evaluated in 18 healthy dogs by thyrotropin (TSH) stimulation. Two dose regimens were used in each dog: 0.1 IU/kg body weight of freshly reconstituted lyophilized TSH and 1 IU/dog of previously frozen and stored TSH (up to 200 days), both given intravenously. Blood samples were collected prior to and at four and six hours after TSH administration. Serum was evaluated for total thyroxine concentrations by radioimmunoassay. All dogs were classified as euthyroid on the basis of response to 0.1 IU/kg body weight of freshly reconstituted TSH at four and six hours. The 1 IU dose of TSH, previously frozen for up to 200 days, induced increases in serum total thyroxine concentration over baseline at four and six hours that were not significantly different from those resulting from the use of the higher dose of fresh TSH. In all test groups, there were no statistically significant differences between total thyroxine concentrations at four and six hours post-TSH administration. It was concluded that an adequate TSH response can be achieved with the use of 1 IU of TSH/dog for clinically normal dogs between 29.0 kg and 41.6 kg body weight, even if this TSH has been frozen at -20 degrees C for up to 200 days. Further, blood collection can be performed at any time between four and six hours. Similar studies are needed to evaluate this new protocol in hypothyroid dogs and euthyroid dogs suffering nonthyroidal systemic diseases.     

Serum thyroid hormone concentrations in clinically normal dogs after administration of freshly reconstituted vs previously frozen and stored thyrotropin

Concentrations of serum thyroxine (T4) and 3,3',5-triiodothyronine (T3) were determined in 7 clinically healthy adult dogs before and after administration of freshly reconstituted thyrotropin (TSH) and TSH that had been previously reconstituted and frozen for 1, 2, and 3 months. The 4 TSH response tests were performed at 30-day intervals by collecting blood samples for serum T4 and T3 determinations before and 4 and 6 hours after IV administration of TSH (0.1 U/kg of body weight). Baseline serum concentrations of T4 and T3 were similar at each of the 4 sample collection times over the 3-month period of the study. Mean serum concentrations of T4 and T3 increased significantly (P less than 0.01) over baseline values after administration of freshly reconstituted TSH or TSH that had been previously frozen for 1, 2, or 3 months. Significant difference was not found in the mean post-TSH serum T4 or T3 concentration after injection of freshly reconstituted TSH or TSH that had been previously frozen for 1, 2, or 3 months. In 2 of the 7 dogs, mild reactions--mild ataxia and weakness--were observed during the last of the series of TSH response tests (ie, after IV administration of TSH that had been previously frozen for 3 months). Results of this study suggest that for use in dogs, reconstituted TSH stored at -20 C maintains adequate biological activity for at least 3 months. The ability to store reconstituted TSH for a longer period than the recommended 48 hours represents an economic advantage, because it allows clinicians to perform more TSH response tests per vial of TSH.     

Evaluation of recombinant human thyroid-stimulating hormone to test thyroid function in dogs suspected of having hypothyroidism

OBJECTIVE: To evaluate the use of recombinant human (rh) thyroid-stimulating hormone (TSH) in dogs with suspected hypothyroidism. ANIMALS: 64 dogs with clinical signs of hypothyroidism. PROCEDURES: Dogs received rhTSH (75 microg/dog, IV) at a dose independent of their body weight. Blood samples were taken before and 6 hours after rhTSH administration for determination of total serum thyroxine (T(4)) concentration. Dogs were placed into 1 of 3 groups as follows: those with normal (ie, poststimulation values indicative of euthyroidism), unchanged (ie, poststimulation values indicative of hypothyroidism; no thyroid gland stimulation), or intermediate (ie, poststimulation values between unchanged and normal values) post-TSH T(4) concentrations. Serum canine TSH (cTSH) concentration was determined in prestimulation serum (ie, before TSH administration). RESULTS: 14, 35, and 15 dogs had unchanged, normal, and intermediate post-TSH T(4) concentrations, respectively. Basal T(4) and post-TSH T(4) concentrations were significantly different among groups. On the basis of basal serum T(4) and cTSH concentrations alone, 1 euthyroid (normal post-TSH T(4), low basal T(4), and high cTSH concentrations) and 1 hypothyroid dog (unchanged post-TSH T(4) concentration and low to with-in reference range T(4) and cTSH concentrations) would have been misinterpreted as hypothyroid and euthyroid, respectively. Nine of the 15 dogs with intermediate post-TSHT(4) concentrations had received medication known to affect thyroid function prior to the test, and 2 of them had severe nonthyroidal disease. CONCLUSIONS AND CLINICAL RELEVANCE: The TSH-stimulation test with rhTSH is a valuable diagnostic tool to assess thyroid function in selected dogs in which a diagnosis of hypothyroidism cannot be based on basal T(4) and cTSH concentrations alone.     

Serum concentrations of thyroxine and 3,5,3'-triiodothyronine in dogs before and after administration of freshly reconstituted or previously frozen thyrotropin-releasing hormone

Concentrations of serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were determined after the administration of freshly reconstituted thyrotropin-releasing hormone (TRH), reconstituted TRH that had been previously frozen, or thyrotropin (TSH) to 10 mature dogs (6 Greyhounds and 4 mixed-breed dogs). Thyrotropin-releasing hormone (0.1 mg/kg) or TSH (5 U/dog) was administered IV; venous blood samples were collected before and 6 hours after administration of TRH or TSH. Concentrations of the T4 and T3 were similar (P greater than 0.05) in serum after administration of freshly reconstituted or previously frozen TRH, indicating that TRH can be frozen at -20 C for at least 1 week without a loss in potency. Concentrations of T4, but not T3, were higher after the administration of TSH than they were after the administration of TRH (P less than 0.01). Concentrations of T4 increased at least 3-fold in all 10 dogs given TSH, whereas a 3-fold increase occurred in 7 of 10 dogs given freshly reconstituted or previously frozen TRH. Concentrations of T4 did not double in 1 dog given freshly reconstituted TRH and in 1 dog given previously frozen TRH. Concentrations of T3 doubled in 5 of 10, 2 of 10, and 5 of 10 dogs given TSH, freshly reconstituted TRH, or previously frozen TRH, respectively. Results suggested that concentrations of serum T4 are higher 6 hours after the administration of TSH than after administration of TRH, using dosage regimens of 5 U of TSH/dog or 0.1 mg of TRH/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs

OBJECTIVE: To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration. DESIGN: Prospective study. ANIMALS: 7 healthy euthyroid dogs. PROCEDURE: Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed. RESULTS: Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.     

Comparison of the biological activity of recombinant human thyroid-stimulating hormone with bovine thyroid-stimulating hormone and evaluation of recombinant human thyroid-stimulating hormone in healthy dogs of different breeds

OBJECTIVE: To evaluate whether use of recombinant human (rh) thyroid-stimulating hormone (TSH) induces equivalent stimulation, compared with bovine TSH (bTSH), and to evaluate activity of rhTSH in dogs of various large breeds. ANIMALS: 18 healthy research Beagles and 20 healthy client-owned dogs of various breeds with body weight > 20 kg. PROCEDURES: The 18 Beagles were randomly assigned to 3 groups, and each dog received either 75 microg of rhTSH, IM or IV, or 1 unit of bTSH, IM, respectively, in a crossover design. The 20 client-owned dogs received 75 microg of rhTSH, IV. Blood samples were taken before and 6 hours after TSH administration for determination of total serum thyroxine (T(4)) concentration. Additional blood samples were taken after 2 and 4 hours in Beagles that received rhTSH, IM. RESULTS: There was a significant increase in T(4) concentration in all dogs, but there were no differences between values obtained after administration of bTSH versus rhTSH or IV versus IM administration of rhTSH. Although there was a significant difference in age and body weight between Beagles and non-Beagles, there was no difference in post-TSH simulation T(4) concentration between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated an equivalent biological activity of rhTSH, compared with bTSH. Use of 75 microg of rhTSH, IV, did not induce a different magnitude of stimulation in large-breed dogs, compared with Beagles. Euthyroidism was confirmed if post-TSH simulation T(4) concentration was > or = 2.5 microg/dL and at least 1.5 times basal T(4) concentration.     

Comparison of two doses of aqueous bovine thyrotropin for thyroid function testing in dogs

Thyroid function was evaluated in 20 healthy dogs by thyrotropin (TSH) response testing. Two dose regimens were used: 5 IU of TSH given IV and 1 IU of TSH given IV. Blood samples were collected prior to and at 4 and 6 hours after TSH administration. Serum was obtained and analyzed for total 3,5,3'-tri-iodothyronine and thyroxine (T4) concentrations by radioimmunoassay. All dogs were classified as euthyroid on the basis of response to 5 IU of TSH at 4 and 6 hours. The 1-IU dose of TSH failed to induce adequate increase in T4 concentration in 7 dogs at 4 and 6 hours when the criteria for normal response were post-TSH serum concentration T4 greater than or equal to 3.0 micrograms/dl and serum T4 increase by greater than or equal to 100% over baseline serum T4 concentration. One IU of TSH induced increase in serum T4 concentration over baseline; however, the increase was significantly (P less than 0.05) less than that in response to a 5-IU dose at 6 hours after administration of TSH.     

Serum-free thyroxine concentrations, measured by chemiluminescence assay before and after thyrotropin administration in healthy dogs, hypothyroid dogs, and euthyroid dogs with dermathopathies.

The purpose of this study was to determine the usefulness of free thyroxine (FT4) measured by chemiluminescence in evaluating thyroid function in dogs. Total thyroxine (TT4) concentration measured by radioimmunoassay (RIA) and FT4 measured by chemiluminescence were evaluated in 30 healthy dogs, 60 euthyroid dogs with concurrent dermatopathies, and 30 hypothyroid dogs before and after intravenous stimulation with 1 or 2 IU of thyrotropin (TSH). Median basal TT4 and median TT4 concentrations at 4 h post-TSH administration were not significantly different (P < 0.0001) between healthy dogs and euthyroid dogs with dermatopathies, but were significantly higher than those in hypothyroid dogs. In healthy dogs, the median TT4 concentrations at 4 and 6 h post-TSH administration were not significantly different. Median basal FT4 and median FT4 concentrations at 4 h post-TSH administration in healthy dogs were significantly lower (P < 0.0001) than those in euthyroid dogs with dermatopathies, but significantly higher than the same parameters in hypothyroid dogs. There was a significant difference between the median FT4 concentrations at 4 h post-TSH administration and median basal FT4 concentrations for healthy dogs and euthyroid dogs with dermatopathies, but not for hypothyroid dogs. Lastly, in healthy dogs, median FT4 concentrations at 4 and 6 h post-TSH administration were not significantly different. Free thyroxine measured by chemiluminescence was highly correlated (P < 0.0001; Spearman r = 0.91) with FT4 measured by the reference method for free hormone analysis, namely, equilibrium dialysis, when sera from 56 dogs were used.     

Assessment of thyroid functional reserve in the cat by the thyrotropin-stimulation test

Serum thyroxine (T4) concentrations before and after various IV doses of bovine thyrotropin (TSH) were measured over a 48-hour period in 19 healthy cats. Base-line T4 values, as measured by radioimmunoassay, varied greatly. The peak T4 concentration occurred 6 hours after TSH injection, and there was an increase in post-TSH serum T4 concentration that was linearly related to the logarithm of the dose. Greatest stimulation was seen with the highest dose used (1 U of TSH/kg of body weight), and 6 hours after administration of this dose, the serum T4 concentration range was 4.1 to 8.4 micrograms/dl. The post-TSH serum T4 concentration and the absolute increase in serum T4 concentration after TSH administration correlated more closely with the TSH dose than did the ratio of post-TSH serum T4 concentration to base-line T4 concentration. Therefore, in cats with normal thyroid-binding protein concentrations, the former indices should represent the most reliable assessment of thyroid functional reserve.     

Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.     

Comparison of 2 Doses of Recombinant Human Thyrotropin for Thyroid Function Testing in Healthy and Suspected Hypothyroid Dogs

Background: Various protocols using different doses of recombinant human thyrotropin (rhTSH) in TSH stimulation testing have been described. However, the influence of TSH dosage on thyroxine (T4) concentration has not yet been evaluated in suspected hypothyroid dogs.
Objective: To evaluate the effectiveness of 2 doses of rhTSH.
Animals: Fifteen dogs with clinical signs consistent with hypothyroidism and abnormal stimulation results with 75 μg rhTSH and 18 clinically healthy dogs.
Methods: All dogs were stimulated with 75 and 150 μg rhTSH IV in a 1st and 2nd stimulation test, respectively. Blood samples were taken before and 6 hours after rhTSH administration for determination of total T4 concentration.
Results: Using the higher dose led to a normal test interpretation in 9 of the 15 dogs, in which stimulation had been abnormal using the lower dose. Based on follow-up information, hypothyroidism was excluded in 7 of these 9 dogs. In all 6 dogs with a blunted response to the higher dose, hypothyroidism could be confirmed. Healthy dogs showed significantly higher post-TSH T4 concentrations with the higher compared with the lower dose. Post-TSH T4 concentrations after TSH stimulation were not related to dogs' body weight in either healthy or diseased dogs.
Conclusions and Clinical Relevance: TSH dose significantly influenced test interpretation in suspected hypothyroid dogs. Differentiation between primary hypothyroidism and nonthyroidal disease was improved with 150 μg rhTSH. Because this effect was independent of the dogs' body weight, the higher dose is recommended in dogs that have concurrent disease or are receiving medication.     

Thyroid function and serum hepatic enzyme activity in dogs after phenobarbital administration

Phenobarbital is the drug of choice for control of canine epilepsy. Phenobarbital induces hepatic enzyme activity, can be hepatotoxic, and decreases serum thyroxine (T4) concentrations in some dogs. The duration of liver enzyme induction and T4 concentration decreases after discontinuation of phenobarbital is unknown. The purpose of this study was to characterize the changes in serum total T4 (TT4), free T4 (FT4), thyroid-stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) after discontinuation of long-term phenobarbital administration in normal dogs. Twelve normal dogs were administered phenobarbital at a dosage of approximately 4.4-6.6 mg/kg PO q12h for 27 weeks. Blood was collected for analysis before and after 27 weeks of phenobarbital administration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T4 and FT4 were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in estimate of thyroid function (TT4, FT4, TSH) persisted for 1-4 weeks after discontinuation of phenobarbital, whereas changes in hepatic enzyme activity (ALT, ALP) and cholesterol concentration resolved in 3-5 weeks. To avoid false positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevated serum activity of hepatic enzymes 6-8 weeks after discontinuation of phenobarbital may indicate hepatic disease.     

Effects of racing and nontraining on plasma thyroid hormone concentrations in sled dogs

OBJECTIVE: To determine the effects of racing and nontraining on plasma thyroxine (T4), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and thyroglobulin autoantibody (TgAA) concentrations in sled dogs and compare results with reference ranges established for dogs of other breeds. DESIGN: Cross-sectional study. ANIMALS: 122 sled dogs. PROCEDURE: Plasma thyroid hormone concentrations were measured before dogs began and after they finished or were removed from the Iditarod Trail Sled Dog Race in Alaska and approximately 3 months after the race. RESULTS: Concentrations of T4 and fT4 before the race were less than the reference range for nonsled dogs in 26% and 18% of sled dogs, respectively. Immediately after racing, 92% of sled dogs had plasma T4 concentrations less than the reference range. Three months after the race, 25% of sled dogs had plasma T4 concentrations less than the reference range. For T4, fT4, TSH, and TgAA, significant differences were not detected in samples collected before the race versus 3 months later. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma T4, fT4, and TSH concentrations decreased in dogs that complete a long distance sled dog race. Many clinically normal sled dogs have plasma T4 and fT4 values that are lower than the reference range for nonsled dogs. We suggest that the reference ranges for sled dogs are 5.3 to 40.3 nmol/L and 3.0 to 24.0 pmol/L for plasmaT4 and fT4 concentrations, respectively, and 8.0 to 370 mU/L for TSH.     

Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease

OBJECTIVE: To determine whether nonthyroidal disease of various causes and severity is associated with abnormalities in baseline serum concentrations of total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone [TSH]) in dogs believed to be euthyroid. DESIGN: Case-control study. ANIMALS: 223 dogs with confirmed nonthyroidal diseases and presumptive normal thyroid function, and 150 clinically normal dogs. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations were measured in dogs with confirmed nonthyroidal disease. Reference ranges for hormone concentrations were established on the basis of results from 150 clinically normal dogs. RESULTS: In dogs with nonthyroidal disease, median serum concentrations of total T4, total T3, and free T4 were significantly lower than those in clinically normal dogs. Median serum TSH concentration in sick dogs was significantly greater than that of clinically normal dogs. When stratified by severity of disease (ie, mild, moderate, and severe), dogs with severe disease had low serum concentrations of total T4, total T3, or free T4 more commonly than did dogs with mild disease. In contrast, serum TSH concentrations were more likely to remain within the reference range regardless of severity of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that serum total T4, free T4, and total T3 concentrations may be low (ie, in the hypothyroid range) in dogs with moderate to severe nonthyroidal disease. Serum TSH concentrations are more likely to remain within the reference range in sick dogs.     

Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in healthy, hypothyroid and euthyroid sick dogs

Recombinant human thyroid-stimulating hormone (rhTSH) was evaluated for the diagnosis of canine hypothyroidism, using TSH response tests. Phase I stimulation tests were performed in 6 healthy dogs weighing over 20 kg, using 50 and then 100 microg of freshly reconstituted rhTSH administered intravenously. In phase II, the same dogs were stimulated by using 100 microg of rhTSH frozen for 3 months at -20 degrees C. Phase III stimulation tests were performed by using 50 or 100 microg of freshly reconstituted or frozen rhTSH in healthy (n = 14), euthyroid sick (n = 11) and hypothyroid dogs (n = 9). A dose of 100 microg of rhTSH was judged more appropriate for dogs weighing more than 20 kg. Biological activity of rhTSH after freezing at -20 degrees C for up to 12 weeks was maintained. When stimulated, significant (P < 0.05) increases in total thyroxine concentration were observed only in healthy and euthyroid sick dogs. Results of this study show that the rhTSH stimulation test is able to differentiate euthyroidism from hypothyroidism in dogs.     

Thyroid function tests in euthyroid dogs treated with L-thyroxine

The effects of treatment with L-thyroxine (1 mg/m2 of body surface/d, PO, for 8 weeks) on the thyroxine (T4) and triiodothyronine (T3) responses to thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) administration were determined in 10 euthyroid Beagles; 4 other dogs acted as controls. The TSH response test was performed before treatment and at weeks 2, 4, and 8 of treatment in all dogs and at 2 and 4 weeks after cessation of treatment in 6 dogs. The TRH response test was performed before treatment and at week 6 of treatment in all dogs and at 5 weeks after cessation of treatment in 6 dogs. Suppression of the T3 response to TSH was evident at treatment week 2, whereas the T4 response was suppressed at week 4 and remained suppressed for the duration of the study. Four weeks after stopping treatment, T4 and T3 responses to TSH in 2 dogs were within the hypothyroid range. The T4 response to TRH was completely suppressed after 6 weeks of thyroxine treatment, but returned to pretreatment values by 5 weeks after cessation of treatment. Suppression of thyroid and pituitary function is evident after administration of a replacement dose of L-thyroxine to euthyroid dogs.     

Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in epileptic dogs treated with anticonvulsants.

OBJECTIVE: To determine whether administration of phenobarbital, potassium bromide, or both drugs concurrently was associated with abnormalities in baseline serum total thyroxine (T4), triiodothyronine (T3), free T4, or thyrotropin (thyroid-stimulating hormone; TSH) concentrations in epileptic dogs. DESIGN: Prospective case series. ANIMALS: 78 dogs with seizure disorders that did not have any evidence of a thyroid disorder (55 treated with phenobarbital alone, 15 treated with phenobarbital and bromide, and 8 treated with bromide alone) and 150 clinically normal dogs that were not receiving any medication. PROCEDURE: Serum total T4, total T3, free T4, and TSH concentrations, as well as serum concentrations of anticonvulsant drugs, were measured in the 78 dogs with seizure disorders. Reference ranges for hormone concentrations were established on the basis of results from the 150 clinically normal dogs. RESULTS: Total and free T4 concentrations were significantly lower in dogs receiving phenobarbital (alone or with bromide), compared with concentrations in clinically normal dogs. Administration of bromide alone was not associated with low total or free T4 concentration. Total T3 and TSH concentrations did not differ among groups of dogs. CLINICAL IMPLICATIONS: Results indicate that serum total and free T4 concentrations may be low (i.e., in the range typical for dogs with hypothyroidism) in dogs treated with phenobarbital. Serum total T3 and TSH concentrations were not changed significantly in association with phenobarbital administration. Bromide treatment was not associated with any significant change in these serum thyroid hormone concentrations.     

Effect of oral administration of sulfadiazine and trimethoprim in combination on thyroid function in dogs.

The effect of oral administration of sulfadiazine and trimethoprim in combination on serum concentrations of thyroxine (T4), triiodothyronine (T3) and free thyroxine (fT4) and the thyroid hormone response to thyrotropin administration was assessed. Six dogs were administered sulfadiazine (12.5 mg/kg) and trimethoprim (2.5 mg/kg) orally for 28 days; six untreated dogs acted as controls. Serum T4, T3 and fT4 were determined weekly during and for four weeks after treatment. Thyrotropin response tests were performed prior to treatment, after four weeks of treatment and three weeks after stopping treatment. There were no significant differences in mean serum T4, T3 or fT4 concentrations between treated and control groups at any time during the study. Mean concentration of serum T4 over time did not differ significantly from baseline concentration in either group. Significant differences in the mean serum T3 and fT4 concentrations occurred at several time points in treatment and control groups, and were apparently unrelated to treatment. Significant differences in the T4 or T3 response to thyrotropin administration within or between groups were not present. Serum T3 and fT4 concentrations fluctuate in normal dogs. Administration of sulfadiazine and trimethoprim in combination does not affect tests of thyroid function in the dog.     

Biological variation of canine serum thyrotropin (TSH) concentration

The aim of the present study was to estimate the between-dog, within-dog and analytical components of variance for serum thyrotropin (TSH) in healthy dogs, and to use these components of variance to 1) estimate the critical difference for significance between serial results; 2) assess the utility of the conventional population-based reference interval; 3) set a desirable performance standard for analytical imprecision; and 4) estimate the number of samples required for determination of the true mean value for an individual dog. Using the Immulite test system, TSH was measured in serum samples collected weekly for five weeks from eight clinically healthy dogs. Results were subjected to nested analysis of variance. Between-dog variation was 43.6%, within-dog variation was 13.6%, analytical variation was 8.8%, the one-sided critical difference was 37.8%, the index of individuality was 0.4, the maximum allowable analytical imprecision was 6.8%, and the number of samples required to determine the true mean value in a single dog was 40. In practical terms, the present study indicated that the analytical imprecision of canine serum TSH measurement should be < 7%, and that comparing a single serum TSH measurement from an individual dog to the conventional population-based reference range may be too insensitive to detect small but important changes in the serum TSH level of that particular dog. In addition, when treating a hypothyroid dog, serum TSH, measured on a weekly basis, should decrease by at least one-third before any effect of exogenous thyroxine supplementation can be said to have influenced the serum TSH level.