Influence of Isoflurane General Anesthesia or Anesthesia and Surgery on Thyroid Function Tests in Dogs

Background: Anesthesia and surgery affect thyroid function tests in humans but have not been studied in dogs. Hypothesis: Anesthesia and anesthesia with surgery will affect thyroid function tests in dogs. Animals: Fifteen euthyroid dogs. Methods: Prospective, controlled, interventional study. Dogs were assigned to one of 3 groups: control, general anesthesia, and general anesthesia plus abdominal exploratory surgery. Dogs in the anesthesia and surgery groups were premedicated with acepromazine and morphine, induced with propofol, and maintained on isoflurane. Samples for measurement of serum thyroxine (T₄), free T₄ (fT₄) by equilibrium dialysis, triiodothyronine (T₃), reverse T₃ (rT₃), and thyroid‐stimulating hormone concentrations were collected from each dog immediately before premedication, at multiple times during anesthesia, surgery, 4, 8, 12, 24, 36, and 48 hours after anesthesia, once daily for an additional 5 days, and once 14 days after anesthesia. Sampling was performed at identical times in the control group. Results: Serum T₄ decreased significantly from baseline in the surgery and anesthesia groups compared with the control group at 0.33 (P= 0.043) and 1 hour (P= 0.018), and 2 (P= 0.031) and 4 hours (P= 0.037), respectively, then increased significantly in the surgery group compared with the control group at 24 hours (P= 0.005). Serum T₃ decreased significantly from baseline in the anesthesia group compared with the control group at 1 hour (P= 0.034). Serum rT₃ increased significantly from baseline in the surgery group compared with the control and anesthesia groups at 8 (P= 0.026) and 24 hours (P= 0.0001) and anesthesia group at 8, 12, 24, and 36 hours (P= 0.004, P= 0.016, P= 0.004, and P= 0.014, respectively). Serum fT₄ increased significantly from baseline in the surgery group compared to the control at 24 hours (P= 0.006) and at day 7 (P= 0.037) and anesthesia group at 48 hours (P= 0.023). Conclusions and Clinical Importance: Surgery and anesthesia have a significant effect on thyroid function tests in dogs.     

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.     

Thyroid Function in Anhidrotic Horses

Background: This study was performed to determine whether anhidrotic horses have altered thyroid function compared with horses that sweat normally.
Hypothesis: Anhidrotic horses have normal thyroid function.
Animals: Ten client-owned horses with clinical signs of anhidrosis were paired with 10 horses living in the same environment that had normal sweat production.
Methods: Horses were diagnosed as having normal sweat production or being anhidrotic based on responses to intradermal injections of terbutaline and physiologic responses to lunging exercise. Control horses were selected from the same environment and matched as closely as possible to anhidrotic horses in terms of age, sex, breed, and athletic condition. Thyrotropin-releasing hormone (TRH) stimulation tests were performed in both horses at the same time, once in the summer or fall, and once again in winter.
Results: Anhidrotic horses produced less sweat in response to intradermal injections of terbutaline and exercise than did control horses. They also had greater increases in body temperature and respiratory rate in response to exercise. Resting concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) were not different between anhidrotic and control horses. Thyroid hormone responses to TRH also were not different between the 2 groups of horses. However, anhidrotic horses had a significantly different TSH response to TRH compared with control horses, particularly in the winter.
Conclusions and Clinical Importance: The biologic relevance of the altered TSH response to TRH in anhidrotic horses is uncertain, considering that TSH concentrations remained within previously reported normal ranges and thyroid hormone responses were not different between anhidrotic and control horses.     

Thyrotropin-releasing hormone stimulation test to assess thyroid function in severely sick cats

Basal serum thyroxine (T4) concentration and the thyrotropin-releasing hormone (TRH) stimulation test were used to assess thyroid function in 36 critically ill cats examined between July 1996 and October 1998. Of the 36 cats. hyperthyroidism (as underlying or complicating disease) was suspected in 22 based on clinical signs, palpable thyroid nodules, and abnormal thyroid gland histology (study group). Hyperthyroidism was not suspected in the remaining 14 cats, which served as the control group. Based on serum T4 concentrations, suppression of thyroid function was documented in 14 (64%) cats of the study group and in 10 (71%) cats of the control group. The TRH stimulation test revealed an increase in serum T4 of less than 50% of the baseline concentration in 18 (82%) cats of the study group, and in 6 (43%) cats of the control group. In conclusion, based on the results of serum T4 determinations and the TRH stimulation tests, it was not possible to differentiate between cats with clinical and histologic evidence of thyroid dysfunction (hyperthyroidism) and cats with severe nonthyroidal illnesses.     

Euthyroid sick syndrome in dogs with idiopathic epilepsy before treatment with anticonvulsant drugs

Euthyroid sick syndrome is a common finding in dogs and is attributable to nonthyroidal illness or treatment with any of a variety of drugs such as phenobarbital. In dogs with epilepsy, treatment with anticonvulsant drugs can lead to subnormal plasma thyroid hormone concentrations despite normal thyroid function. One-hundred thirteen dogs with seizure activity were retrospectively evaluated to determine the influence of idiopathic epilepsy (IE) on thyroid hormone concentrations. Blood samples were taken from 60 dogs with IE before initiation of anticonvulsant therapy. Control groups consisted of 34 dogs with IE and receiving anticonvulsants and 19 dogs with secondary epilepsy. Thyroid concentrations consistent with euthyroid sick syndrome were diagnosed in 38% of dogs with untreated IE without clinical signs of hypothyroidism or concomitant diseases. There was a significant correlation (r = 0.363, P = .01) between seizure frequency and plasma thyroid hormone concentrations: the longer the interval between 2 seizure events, the higher the serum total thyroxine concentration. There was no correlation between the degree of alteration of thyroid hormone concentrations and the time span between the most recent seizure event and blood collection, the type of the most recent seizure event, the duration of the complete seizure history, or the predominant seizure type. These results suggest that IE can be a reason for euthyroid sick syndrome in dogs. The effect of phenobarbital on plasma thyroid hormone concentrations must be investigated in future studies, as it might be less pronounced than expected.     

Pharmacokinetics of Total Thyroxine after Repeated Oral Administration of Levothyroxine Solution and its Clinical Efficacy in Hypothyroid Dogs

Background

Oral levothyroxine (l‐T₄) supplementation is commonly used to treat hypothyroid dogs.

Objectives

Investigate the plasma profile and pharmacokinetics of total thyroxine (tT₄) after PO administration of a l‐T₄ solution and its clinical efficacy in hypothyroid dogs.

Animals

Ten dogs with naturally occurring hypothyroidism.

Methods

After hypothyroidism diagnosis and supplementation with l‐T₄ solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT₄ were determined over 34 hours and the clinical condition of the dogs was evaluated.

Results

Before dosing for pharmacokinetic evaluation, mean tT₄ concentration was 23 ± 9 nmol/L. l‐T₄ was absorbed rapidly (t _max, 5 hours), reaching a mean maximal tT₄ concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.

Conclusions and Clinical Importance

The pharmacokinetics of l‐T₄ in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T₄ solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.     

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.     

Optimal Testing for Thyroid Hormone Concentration after Treatment with Methimazole in Healthy and Hyperthyroid Cats

Background: Methimazole suppresses thyroid hormone synthesis and is commonly used to treat feline hyperthyroidism. The degree of variation in thyroid hormone concentrations 24 hours after administration of methimazole and optimal time for blood sampling to monitor therapeutic efficacy have not been determined.
Objective: To assess thyroid hormone concentration variation in serum of normal and hyperthyroid cats after administration of methimazole.
Animals: Four healthy cats and 889 retrospectively acquired feline thyroid hormone profiles.
Methods: Crossover and retrospective studies . In the crossover study, healthy cats were treated with increasing doses of oral methimazole until steady state of thyroid suppression was achieved. Thyroid hormones and thyroid stimulating hormone (TSH) were serially and randomly monitored after methimazole. Paired t -tests and a 3-factor analysis of variance were used to determine differences between thyroid hormone concentrations in treated and untreated cats in the crossover study. Thyroid profiles from methimazole-treated hyperthyroid cats were retrieved from the Diagnostic Center for Population and Animal Health database and reviewed. Linear regression analysis evaluated relationships of dosage (mg/kg), dosing interval (q24h versus q12h), and time after methimazole to all thyroid hormone concentrations.
Results: All serum concentrations of thyroid hormones were significantly suppressed and TSH was significantly increased for 24 hours after administration of oral methimazole in healthy cats ( P < .005). In hyperthyroid cats, there were no significant relationships between thyroid hormone concentrations and time postpill or dosing interval.
Conclusions: Timing of blood sampling after oral methimazole administration does not appear to be a significant factor when assessing response to methimazole treatment.     

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.     

Effect of a Limited Iodine Diet on Iodine Uptake by Thyroid Glands in Hyperthyroid Cats

Background

The effect of feeding a limited iodine diet on radioactive iodine uptake in the thyroid glands of hyperthyroid cats is unknown.

Objectives

To determine how feeding limited dietary iodine affects radioactive iodine uptake by the thyroid glands of hyperthyroid cats.

Animals

Eight geriatric cats with spontaneous hyperthyroidism.

Methods

Prospective study of eight client owned hyperthyroid cats fed a commercially available iodine limited diet for 6 months. Clinical signs were evaluated and TT4 and fT4 were measured during consumption of the diet. Uptake of ¹²³I was determined before and 8–16 weeks after exclusive consumption of the diet.

Results

Clinical signs of hyperthyroidism resolved in all cats, but there was no significant increase in body weight. TT4 and fT4 decreased into the reference range by 8–16 weeks in all cats. Mean TT4 before consumption of the diet was 9.7 μg/dL (SD 5.2) and after consumption of the diet was 3.1 μg/dL (SD 0.9). Scintigraphy revealed unilateral uptake of isotope in 5 cats and bilateral uptake in 3 cats. Mean percentage uptake of ¹²³I by the thyroid gland at 8 hours after isotope administration was 16.2 (SD 11.8) before diet consumption and 34.6 (SD 11.7) 8–16 weeks after exclusive consumption of the diet. The percentage increase was variable between cats (38–639%).

Conclusions and clinical importance

Limited iodine diets increase iodine uptake in the autonomous thyroid glands of hyperthyroid cats. Further studies are necessary to determine if consumption of a limited iodine diet changes sensitivity of the thyroid gland to ¹³¹I treatment.