Effects of phenobarbital treatment on serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs.

OBJECTIVE: To determine whether phenobarbital treatment of epileptic dogs alters serum thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations. DESIGN: Cross-sectional study. ANIMALS: 78 epileptic dogs receiving phenobarbital (group 1) and 48 untreated epileptic dogs (group 2). PROCEDURE: Serum biochemical analyses, including T4 and TSH concentrations, were performed for all dogs. Additional in vitro analyses were performed on serum from healthy dogs to determine whether phenobarbital in serum interferes with T4 assays or alters free T4 (fT4) concentrations. RESULTS: Mean serum T4 concentration was significantly lower, and mean serum TSH concentration significantly higher, in dogs in group 1, compared with those in group 2. Thirty-one (40%) dogs in group 1 had serum T4 concentrations less than the reference range, compared with 4 (8%) dogs in group 2. All dogs in group 2 with low serum T4 concentrations had recently had seizure activity. Five (7%) dogs in group 1, but none of the dogs in group 2, had serum TSH concentrations greater than the reference range. Associations were not detected between serum T4 concentration and TSH concentration, age, phenobarbital dosage, duration of treatment, serum phenobarbital concentration, or degree of seizure control. Signs of overt hypothyroidism were not evident in dogs with low T4 concentrations. Addition of phenobarbital in vitro to serum did not affect determination of T4 concentration and only minimally affected fT4 concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicians should be aware of the potential for phenobarbital treatment to decrease serum T4 and increase TSH concentrations and should use caution when interpreting results of thyroid tests in dogs receiving phenobarbital.     

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.     

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.     

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.     

Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy

OBJECTIVE: To determine whether there are therapeutically relevant changes in serum phenobarbital concentrations throughout a daily dosing interval in epileptic dogs receiving phenobarbital for > or = 3 weeks. DESIGN: Prospective study. ANIMALS: 33 epileptic dogs receiving phenobarbital. PROCEDURE: Serum phenobarbital concentrations were measured at 0 hour (trough), 3 hours, and 6 hours after oral administration of phenobarbital in epileptic dogs that had received phenobarbital twice daily for a minimum of 3 weeks. For each dog, trough, 3-hour, and 6-hour serum phenobarbital concentrations were evaluated to determine whether they were within the same therapeutic category (lower, middle, or upper end of the therapeutic range of 15 to 45 micrograms/ml), or whether there was a > 30% change in serum concentrations throughout the day. RESULTS: Ninety-one percent (30/33) of dogs had trough, 3-hour, and 6-hour serum phenobarbital concentrations in the same therapeutic category. Only 9% (3/33) of dogs had trough, 3-hour, and 6-hour serum concentrations in different therapeutic categories with a > 30% change in concentrations throughout the day. Significant differences were not detected among mean serum phenobarbital concentrations when comparing the trough, 3-hour, and 6-hour samples for all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: There is no therapeutically relevant change in serum phenobarbital concentrations throughout a daily dosing interval in most epileptic dogs. Therefore, timing is not important when collecting blood samples to measure serum phenobarbital concentrations in most epileptic dogs treated long-term with phenobarbital.     

Tertiary hypothyroidism in a dog

: A nine-year-old male entire Labrador was diagnosed with pituitary dependent hyperadrenocorticism. Following seven months of successful mitotane therapy, the dog presented with marked weight gain, seborrhoea and alopecia. Routine clinicopathological analyses revealed marked hypercholesterolaemia. Serum total and free thyroxine (T4) concentrations were below their respective reference ranges. Serum thyroid stimulating hormone (cTSH) concentration was within reference range. TSH and thyrotropin releasing hormone (TRH) response tests revealed adequate stimulation of total T4 in both, and cTSH in the latter test. Magnetic resonance imaging revealed a mass arising from the pituitary fossa, with suprasellar extension. A diagnosis of tertiary hypothyroidism was made. Following four weeks of levothyroxine therapy, circulating cholesterol concentration had declined, weight loss had ensued and dermatological abnormalities had improved. Euthanasia was performed four months later due to the development of neurological signs. A highly infiltrative pituitary adenoma, with effacement of the overlying hypothalamus was identified on post mortem examination. Tertiary hypothyroidism has not been previously reported in dogs.     

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.     

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.     

Serum triglyceride concentration in dogs with epilepsy treated with phenobarbital or with phenobarbital and bromide

OBJECTIVE: To compare serum triglyceride concentrations obtained after food had been withheld (i.e., fasting concentrations) in dogs with epilepsy that had been treated long term (> or = 3 months) with phenobarbital or with phenobarbital and potassium bromide with concentrations in healthy control dogs. DESIGN: Cross-sectional study. ANIMALS: 57 epileptic dogs that had been treated with phenobarbital (n=28) or with phenobarbital and bromide (29) and 57 healthy, untreated control dogs matched on the basis of age, breed, sex, neuter status, and body condition score. PROCEDURES: Blood samples were collected after food had been withheld for at least 12 hours, and serum biochemical and lipid concentrations were determined. Oral fat tolerance tests were performed in 15 control dogs and 9 dogs with epilepsy treated with phenobarbital alone. RESULTS: 19 of the 57 (33%) epileptic dogs had fasting serum triglyceride concentrations greater than the upper reference limit. Nine (16%) dogs had a history of pancreatitis, and 5 of the 9 had high fasting serum triglyceride concentrations at the time of the study. A significant relationship was found between body condition score and fasting serum triglyceride concentration in all dogs, but serum triglyceride concentration was not significantly associated with phenobarbital dosage or serum phenobarbital concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dogs treated long term with phenobarbital or with phenobarbital and bromide may develop hypertriglyceridemia. Fasting serum triglyceride concentration should be periodically monitored in dogs treated with phenobarbital because hypertriglyceridemia is a risk factor for pancreatitis.     

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.     

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.     

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 long-term phenobarbital treatment on the thyroid and adrenal axis and adrenal function tests in dogs

Phenobarbital can interfere with the thyroid axis in human beings and rats by accelerating hepatic thyroxine metabolism because of enzyme induction. In human beings, it also can interfere with the low-dose dexamethasone suppression test (LDDST) used to assess adrenal function by accelerating dexamethasone metabolism. This effect can cause a lack of suppression of pituitary ACTH and subsequent adrenal cortisol release after dexamethasone administration. The effects of phenobarbital on the thyroid axis, the adrenal axis, and adrenal function tests were prospectively investigated in 12 normal, adult dogs. Phenobarbital was administered at 5 mg per kilogram of body weight (range, 4.8–6.6 mg/kg) PO q12h for 29 weeks, resulting in therapeutic serum concentrations (20–40 μg/mL). Serum total thyroxine (TT4), free thyroxine (FT4) by equilibrium dialysis, total triiodothyronine (TT3), thyrotropin (TSH), and cholesterol were determined before and during phenobarbital treatment. LDDST, ACTH stimulation tests, and ultra-sonographic evaluation of the adrenal glands were performed before and during treatment. TT4 and FT4 decreased significantly ( P ≤ .05), TT3 had minimal fluctuation, TSH had only a delayed compensatory increase, and cholesterol increased during phenobarbital treatment. The delayed increase in TSH, despite persistent hypothyroxinemia, suggests that accelerated hepatic thyroxine elimination may not be the only effect of phenobarbital on the thyroid axis. There was no significant effect of phenobarbital on either of the adrenal function tests. With the methods employed, we did not find any effects of the drug on the hormonal equilibrium of the adrenal axis.     

Assessment of thyroid function in dogs with low plasma thyroxine concentration

BACKGROUND: Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. HYPOTHESIS: The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. ANIMALS: In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. METHODS: The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. RESULTS: Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.     

Hepatotoxicity of phenobarbital in dogs: 18 cases (1985-1989).

The medical records of 18 dogs that had hepatic disease and received phenobarbital as an anticonvulsant for 5 to 82 months were reviewed. Clinical signs included sedation and ataxia in all dogs, 5 dogs were also anorectic, 2 had coagulopathy, 3 were icteric, and 5 had ascites. Serum biochemical analysis revealed serum albumin concentration less than or equal to 2.2. g/dl in 12 dogs, serum alkaline phosphatase activity greater than or equal to 169 U/L in 18 dogs, serum alanine transaminase activity greater than or equal to 57 U/L in 15 dogs, and total bilirubin concentration greater than or equal to 1 mg/dl (in the absence of lipemia) in 7 dogs. Serum phenobarbital concentration was greater than or equal to 40 micrograms/ml in 12 of 17 dogs. Sulfobromophthalein excretion was prolonged in 8 of 10 dogs. Preprandial serum bile acid concentrations were high in 8 of 10 dogs, and 2-hour postprandial serum bile acid concentrations were high in 9 of 10 dogs. Two of 4 dogs tested had resting plasma ammonia concentrations greater than 200 mg/dl. An ammonia tolerance test was performed on 2 other dogs; both had ammonia concentration greater than or equal to 200 mg/dl in the plasma 30 minutes after receiving 100 mg of ammonium chloride/kg of body weight, PO. Nine dogs died, 1 was euthanatized, and necropsies were performed on these 10 dogs. Biopsies and necropsies of 6 dogs revealed chronic hepatic fibrosis with nodular regeneration (cirrhosis). One dog had hepatocellular carcinoma and mild cirrhosis. In 1 dog, after phenobarbital had been withheld, necropsy revealed complete recovery of the previously observed lesions.     

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.     

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.     

Effects of thyrotropin-releasing hormone on serum concentrations of thyroxine and triiodothyronine in healthy, thyroidectomized, thyroxine-treated, and propylthiouracil-treated dogs

Effects of thyrotropin-releasing hormone (TRH) on serum concentrations of thyroid hormones were studied in 36 mixed-bred dogs. Dogs were randomly assigned to 7 groups. Significant increases (P less than 0.05) of serum thyroxine (T4) values occurred as early as 2 hours and reached a peak at 6 to 8 hours after IV injection of 300 to 1,100 micrograms of TRH. Thyroxine concentrations in response to a TRH dose greater than 500 micrograms were similar to those observed with the 300-micrograms dose. Transient coughing, vomiting, salivation, and defecation after large doses (900 and 1,100 micrograms) were observed. Mean serum T4 concentration decreased from 2.1 micrograms/dl to 0.9 micrograms/dl within 1 day of thyroidectomy. Clinical signs of hypothyroidism, including lethargy, dry coats, and diffuse alopecia, were present in 2 dogs at a month after surgical operation. Thyroxine concentrations were detectable for greater than 2 months. Injection (IV) of 700 micrograms of TRH 6 weeks after surgical operation had no effect on serum concentration of T4 in thyroidectomized dogs. In 5 T4-treated dogs, TRH (700 micrograms, IV) significantly increased the serum T4 value, indicating that pituitary thyrotropes were responsive to TRH, in spite of daily medication of 0.8 mg of T4. Four dogs were treated orally with 200 mg of propylthiouracil/day for 5 weeks. Intravenous injection of 700 micrograms of TRH in propylthiouracil-treated dogs had no effect on the serum T4 concentration, indicating that TRH had no effect on serum T4 values in these dogs during the experimental period. These results indicate that TRH can replace bovine thyrotropin for the canine thyroid function test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of sulfamethoxazole-trimethoprim on thyroid function in dogs

OBJECTIVE: To evaluate effects of trimethoprim-sulfamethoxazole (T/SMX) on thyroid function in dogs. ANIMALS: 6 healthy euthyroid dogs. PROCEDURE: Dogs were administered T/SMX (14.1 to 16 mg/kg, PO, q 12 h) for 3 weeks. Blood was collected weekly for 6 weeks for determination of total thyroxine (TT4), free thyroxine (fT4), and canine thyroid-stimulating hormone (cTSH) concentrations. Schirmer tear tests were performed weekly. Blood was collected for CBC prior to antimicrobial treatment and at 3 and 6 weeks. RESULTS: 5 dogs had serum TT4 concentrations equal to or less than the lower reference limit, and 4 dogs had serum fT4 less than the lower reference limit after 3 weeks of T/SMX administration; cTSH concentrations were greater than the upper reference limit in 4 dogs. All dogs had TT4 and fT4 concentrations greater than the lower reference limit after T/SMX administration was discontinued for 1 week, and cTSH concentrations were less than reference range after T/SMX administration was discontinued for 2 weeks. Two dogs developed decreased tear production, which returned to normal after discontinuing administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of T/SMX at a dosage of 14.1 to 16 mg/kg, PO, every 12 hours for 3 weeks caused decreased TT4 and fT4 concentrations and increased cTSH concentration, conditions that would be compatible with a diagnosis of hypothyroidism. Therefore, dogs should not have thyroid function evaluated while receiving this dosage of T/SMX for >2 weeks. These results are in contrast to those of a previous study of trimethoprim-sulfadiazine.     

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.