EFFECTS OF METHIMAZOLE ON THYROID GLAND UPTAKE OF 99MTC-PERTECHNETATE IN 19 HYPERTHYROID CATS

Nineteen cats with abnormally high serum T4 concentrations underwent thyroid scintigraphy using technetium-99m pertechnetate (99mTcO4) before and after 36 +/- 6 days of methimazole administration (approximately 2.5mg PO q 12 h). Thyroid-to-salivary gland ratios (T:S ratios) and percentage thyroidal uptake of injected radioactivity at 20 and 60min after injection of 99mTcO4 were compared before and after methimazole treatment. Serum thyroid stimulating hormone (TSH) concentration was measured before and after methimazole treatment. Quantitatively, there was a positive association between the thyroid uptake of 99mTcO4 and the serum T4 before treatment (r = 0.74-0.83). TSH suppression was present when cats were first evaluated for hyperthyroidism. Methimazole treatment did not relieve TSH suppression in 17 cats. Two cats with unilateral thyroid uptake developed bilateral, asymmetric thyroid uptake of 99mTcO4 after treatment and had the greatest increase in TSH concentration after treatment. Quantitatively, thyroid scintigraphy did not significantly change after methimazole treatment (P>0.1). Evaluation of serum TSH concentration may be helpful in identifying methimazole-induced changes in the scintigraphic features of hyperthyroidism in mildly hyperthyroid cats.     

COMPUTED TOMOGRAPHIC CHARACTERISTICS OF THE THYROID GLANDS IN EIGHT HYPERTHYROID CATS PRE‐ AND POSTMETHIMAZOLE TREATMENT COMPARED WITH SEVEN EUTHYROID CATS

Hyperthyroidism is the most common feline endocrinopathy; thyroid computed tomography (CT) may improve disease detection and methimazole dose selection. Objectives of this experimental pre‐post with historical case‐control study were to perform thyroid CT imaging in awake or mildly sedated hyperthyroid cats, compare thyroid gland CT appearance in euthyroid and hyperthyroid cats pre‐ and postmethimazole treatment, and determine whether thyroid size or attenuation correlate with methimazole dose needed for euthyroidism. Premethimazole treatment, eight hyperthyroid cats received CT scans from the head to heart, which were compared to CT of seven euthyroid cats. Total thyroxine levels were monitored every 3–4 weeks. Postmethimazole CT was performed 30 days after achieving euthyroid status. Computed tomography parameters recorded included thyroid length, width, height, attenuation, and heterogeneity. Median time between CT was 70 days (53–213 days). Mild sedation was needed in five hyperthyroid cats premethimazole, and none postmethimazole. Thyroid volume was significantly larger in hyperthyroid cats compared to euthyroid cats (785.0 mm³ vs. 154.9 mm³; P = 0.002) and remained unchanged by methimazole treatment (?4.5 mm3; P = 0.50). Thyroid attenuation and heterogeneity decreased with methimazole treatment (96.1 HU vs. 85.9 HU; P = 0.02. 12.4 HU vs. 8.1 HU; P = 0.009). Methimazole dose ranged from 2.5 to 10 mg daily with a positive correlation between pretreatment thyroid gland volume and dose needed to achieve euthyroidism (P = 0.03). Euthyroid and hyperthyroid cats are easily imaged awake or mildly sedated with CT. Methimazole in hyperthyroid cats significantly lowers thyroid attenuation and heterogeneity, but not size.     

Bioavailability of transdermal methimazole in a pluronic lecithin organogel (PLO) in healthy cats

The antithyroid drug methimazole is widely used for the medical management of feline hyperthyroidism. Recently, custom veterinary pharmacies have offered methimazole in a transdermal gel containing pluronic and lecithin (PLO), with anecdotal evidence of efficacy. The purpose of this study was to determine the bioavailability, relative to i.v. and oral routes of administration, of transdermal methimazole in a PLO gel in cats. Six healthy adult cats were assigned to receive 5 mg of methimazole by the i.v., oral, or transdermal routes, in a randomized triple crossover protocol with 1 week washout between doses. Blood samples were taken for high performance liquid chromatography (HPLC) determination of serum methimazole, at 0, 5, 15, 30, 60 min, and 2, 4, 6, 12 and 24 h after dosing. Methimazole absorption following transdermal administration was poor and variable, with only two of six cats achieving detectable serum methimazole concentrations at any time point following transdermal administration. Area under the concentration-time curve (AUC), maximum concentration (Cmax), and absolute bioavailability were all significantly lower for the transdermal route (0.39 +/- 0.63 microg h/mL, 0.05 +/- 0.09 microg/mL, and 11.4 +/- 18.7%, respectively) than for either i.v. (7.96 +/- 4.38 microg h/mL, 3.34 +/- 2.00 microg/mL, 100%) or oral routes (2.94 +/- 1.24 microg h/mL, 0.51 +/- 0.15 microg/mL, 40.4 +/- 8.1%). The results of this study indicate generally low to undetectable bioavailability of methimazole in a lecithin/pluronic gel given as a single transdermal dose to healthy cats, although one individual cat did achieve nearly 100% transdermal bioavailability relative to the oral route.     

Duration of T4 Suppression in Hyperthyroid Cats Treated Once and Twice Daily with Transdermal Methimazole

Background

Transdermal methimazole is an acceptable alternative to oral treatment for hyperthyroid cats. There are, however, no studies evaluating the duration of T4 suppression after transdermal methimazole application. Such information would be valuable for therapeutic monitoring.

Objective

To assess variation in serum T4 concentration in hyperthyroid cats after once‐ and twice‐daily transdermal methimazole administration.

Animals

Twenty client‐owned cats with newly diagnosed hyperthyroidism.

Methods

Methimazole was formulated in a pluronic lecithin organogel‐based vehicle and applied to the pinna of the inner ear at a starting dose of 2.5 mg/cat q12h (BID group, 10 cats) and 5 mg/cat q24h (SID group, 10 cats). One and 3 weeks after starting treatment, T4 concentrations were measured immediately before and every 2 hours after gel application over a period of up to 10 hours.

Results

Significantly decreased T4 concentrations were observed in week 1 and 3 compared with pretreatment concentrations in both groups. All cats showed sustained suppression of T4 concentration during the 10‐hour period, and T4 concentrations immediately before the next methimazole treatment were not significantly different compared with any time point after application, either in the BID or SID groups.

Conclusions

Because transdermal methimazole application led to prolonged T4 suppression in both the BID and SID groups, timing of blood sampling does not seem to be critical when assessing treatment response.     

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.     

Lack of circulating thyroid stimulating immunoglobulins in cats with hyperthyroidism

Although feline hyperthyroidism has become a commonly diagnosed disorder of older cats, the underlying etiology remains unknown. Pathological findings of adenomatous hyperplasia involving both thyroid lobes in most hyperthyroid cats suggests the possibility that feline hyperthyroidism may be similar to human Graves' disease, which results from high circulating levels of thyroid stimulating immunoglobulins (TSIs). To exclude high circulating levels of TSIs as the cause of feline hyperthyroidism, we measured intracellular concentrations of cyclic adenosine monophosphate (cAMP) in functioning rat thyroid cells (FRTL-5) incubated with IgG extracted from hyperthyroid cat serum. Since TSIs stimulate thyroid hormone secretion through activation of cAMP, their presence can be evidenced in vitro by generation of high cAMP concentrations in cultured thyroid cells. No significant difference was found in intracellular cAMP concentrations in FRTL-5 cells incubated with IgG from normal versus hyperthyroid cats. In contrast, IgG from a human patient with Graves' disease caused substantially more cAMP generation than either normal human IgG or IgG from the cats of this study. These results indicate that feline hyperthyroidism does not result from high circulating concentrations of TSI and, in that respect, is not analogous to Graves' disease.     

Comparison of the effects of daily and intermittent-dose calcitriol on serum parathyroid hormone and ionized calcium concentrations in normal cats and cats with chronic renal failure

BACKGROUND: Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy. HYPOTHESIS: Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia. ANIMALS: Ten normal cats; 10 cats with chronic renal failure. METHODS: Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration. RESULTS: Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated. CONCLUSIONS AND CLINICAL IMPORTANCE: At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and cats with chronic renal failure. With these dosages, adverse affects of calcitriol administration were not seen. Potential reasons for lack of apparent effect include small sample size, insufficient duration of study, insufficient dosage of calcitriol, problems with formulation or administration of calcitriol, and variable gastrointestinal absorption of calcitriol.     

ULTRASONOGRAPHIC EXAMINATION OF THE THYROID GLAND OF HYPERTHYROID CATS: COMPARISON TO 99mTcO−4 SCINTIGRAPHY

High-resolution ultrasonography was evaluated as an alternative to ^99mTcO^-₄ scintigraphy for examining size and appearance of thyroid glands in hyperthyroid cats. Thyroid ultrasound examinations were performed on 6 normal cats and 14 cats with hyperthyroidism. Thyroid lobe volume was estimated from ultrasound images using the equation for a prolate ellipsoid, π/6 (length * height * width). Total thyroid volume was estimated by adding the volume estimations of the left and right lobes. Thyroid lobes of hyperthyroid cats were considered abnormal if estimated volume exceeded the 99% confidence interval for normal thyroid volume determined from the control group. Scintigraphic examinations performed on hyperthyroid cats were evaluated for unilateral versus bilateral disease and for the presence of ectopic activity. Mean thyroid lobe volume and total thyroid volume for normal cats was 85 and 169 mm³, respectively. Mean thyroid lobe volume and total thyroid volume for hyperthyroid cats was 578 and 889 mm³. There was a significant difference in mean estimated total thyroid volume of normal and hyperthyroid cats. Thyroid lobes with greater than normal TcO^-₄ uptake on scintigraphy were larger and had variable homogeneity, echogenicity, and margination on ultrasound examination. There also was an 85.7% agreement of scintigraphy and ultrasonography in differentiating normal from abnormal thyroid lobes. A fair correlation between estimated total thyroid volume of hyperthyroid cats and most recent pretherapy serum thyroxine values were also found. This preliminary study indicates that thyroid ultrasound examination may provide information that is useful for diagnosis and treatment of feline hyperthyroidism. Although ultrasound provides accurate evaluation of the thyroid glands, it cannot replace ^99mTcO^-₄ scintigraphy for screening of metastatic lesions and ectopic glands.     

Thyroid testing in Sloughis

Background: Thyroid hormone concentrations were found to be different in Greyhounds and Whippets compared with nonsight hound dogs.
Hypothesis: In Sloughis, thyroid hormone concentration is lower than in nonsight hounds and comparable to Greyhounds.
Animals: Fifty-one Sloughis with no evidence of disease and a mean age of 4 years (range, 1–12 years).
Methods: Thyroid profiles consisting of total thyroxine (tT4), free thyroxine (fT4), free thyroxine after equilibrium dialysis (fT4 after ED), canine thyroid stimulation hormone (cTSH), and thyroglobulin antibodies as well as CBC and serum biochemistry results of Sloughis were compared with those of normal dogs. In 8 Sloughis, TSH stimulation tests were performed.
Results: In Sloughis, tT4 concentrations and fT4 concentrations measured by chemiluminescence were lower than those of controls (1.13 ± 0.65 μg/dL compared with 2.9 ± 0.8 μg/dL, P < .0001 and 11 ± 4.3 pmol/L compared with 16.7 ± 5.2 pmol/L, P < .0001, respectively). Concentrations of fT4 after ED and TSH were increased in Sloughis, when compared with controls (41.3 ± 26.9 pmol/L compared with 20.98 ± 10.29 pmol/L, P < .0001 and 0.22 ± 0.15 pmol/L compared with 0.15 ± 0.13 pmol/L, P = .0138, respectively). T4 concentration after TSH stimulation increased from 1.5 μg/dL (range, 0.2–2.7 μg/dL) to 2.7 μg/dL (range, 1.2–4.7 μg/dL); the recommended post-TSH T4 concentration was achieved by only 3 of 8 Sloughis. Hemoconcentration was found in 84.3% and hypoglobulinemia in 80.3%.
Conclusions and Clinical Importance: When evaluating Sloughis for hypothyroidism, veterinarians should be aware that these dogs have different thyroid hormone concentrations than nonsight hound dogs.     

Adenohypophyseal Function in Dogs with Primary Hypothyroidism and Nonthyroidal Illness

Background: A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes.
Hypothesis: Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI).
Animals: Fourteen dogs with spontaneous PH and 13 dogs with NTI.
Methods: Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment.
Results: In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups.
Conclusions and Clinical Importance: Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.     

Retinol-Binding Protein in Serum and Urine of Hyperthyroid Cats before and after Treatment with Radioiodine

Background: Retinol-binding protein (RBP) is suggested as a clinically useful marker of renal function in cats.
Hypothesis: Serum and urinary RBP concentrations in hyperthyroid (HT) cats differ from those in healthy (H) cats; radioiodine (¹³¹I) treatment influences serum and urinary RBP concentrations in HT cats.
Animals: Ten HT and 8 H cats.
Methods: RBP concentration was evaluated in feline serum and urine samples from a prospective study.
Results: There was a significant ( P = .003) difference in the urinary RBP/creatinine (uRBP/c) ratios of H (−) and untreated HT (1.4 ± 1.5 × 10⁻² μg/mg) cats. Serum total thyroxine concentration (1.8 ± 1.9 μg/dL, 24 weeks) and uRBP/c (0.6 ± 1.0 × 10⁻² μg/mg, 24 weeks) decreased significantly ( P < .001) in HT cats at all time points after treatment with ¹³¹I, and these variables were significantly correlated with one another ( r = 0.42, P = .007). Serum RBP concentrations from HT cats (199 ± 86 μg/L) did not differ significantly ( P = .98) from those of H cats (174 ± 60) and did not change after treatment with ¹³¹I (182 ± 124 μg/L, P = .80).
Conclusion and Clinical Importance: The presence of urinary RBP in HT cats is a potential marker of tubular dysfunction that is correlated to thyroid status, although it is independent of circulating RBP concentrations. The decreased uRBP/c combined with the absence of changes in serum RBP after treatment suggests that the suspected tubular dysfunction was partly reversible with treatment of ¹³¹I.     

QUALITATIVE AND QUANTITATIVE THYROID IMAGING IN FELINE HYPERTHYROIDISM USING TECHNETIUM-99M AS PERTECHNETATE

Thyroid imaging using technetium-99m as pertechnetate (^99mTcO₄) was carried out in five healthy, euthyroid and 37 hyperthyroid cats using both pinhole and parallel-hole collimators. Images of greater resolution, necessary to distinguish bilateral lobe involvement, were obtained using the pinhole collimator. Per cent thyriod ^99mTcO₄ - uptake was calculated in each cat and was significanly (P < 0.001) higher in hyperthyroid compared with euthyroid cats. In the hyperthyroid cats, per cent thyroid uptake was significantly correlated with serum total thyroxine (T4) and triiodothyronine (T3) Concentrations. Per cent thyroid ^99mTcO₄ - uptake is increased in feline hyperthyrodism and may be calculated using a pinhole collimator alone at the time of qalitative assessment of the extent of thyroid tissue involvement.     

Pharmacokinetics of methimazole in normal cats and cats with hyperthyroidism

The intravenous and oral disposition of the antithyroid drug methimazole was determined in 10 clinically normal cats and nine cats with naturally occurring hyperthyroidism. After intravenous administration of 5 mg methimazole, the mean residence time was significantly (P less than 0.05) shorter in the cats with hyperthyroidism than in the normal cats, but there was no significant difference between the mean values for total body clearance (CL), steady state volume of distribution (Vdss), terminal elimination rate constant (ke), or serum terminal half-life (t1/2) in the two groups of cats. After oral administration, the mean bioavailability of methimazole was high in both the normal cats (77.6 per cent) and cats with hyperthyroidism (79.5 per cent). The values for mean residence time, ke and serum terminal t1/2 after oral dosing were significantly shorter in the cats with hyperthyroidism than in the normal cats. However, after oral administration of methimazole there were no significant differences between the mean values for CL, Vdss, bioavailability and maximum serum concentrations or the time for maximal concentrations to be reached in the two groups of cats. Overall, most pharmacokinetic parameters for methimazole were not altered by the hyperthyroid state. However, the cats with hyperthyroidism did show a trend toward faster elimination of the drug compared with the normal cats, similar to what has been previously described for the antithyroid drug propylthiouracil in cats. These results also indicate that methimazole is well absorbed when administered orally and has a higher bioavailability than that of propylthiouracil in cats with hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

N-acetyl-beta-D-glucosaminidase index as an early biomarker for chronic kidney disease in cats with hyperthyroidism

Background: Hyperthyroid cats are at risk of developing azotemic chronic kidney disease (CKD) and diagnostic tools currently used to screen for CKD in hyperthyroid cats are either unreliable or impractical.
Hypothesis: Urine N -acetyl-β- d -glucosaminidase index (NAG_i) is a good biomarker for azotemic CKD in hyperthyroid cats.
Animals: Twenty-four newly diagnosed nonazotemic hyperthyroid cats and 10 healthy cats.
Methods: All cats were evaluated for hyperthyroidism at baseline. Hyperthyroid cats were treated with methimazole and reevaluated once euthyroid. At the end of the study, cats were divided into 3 groups: healthy cats, nonazotemic, and azotemic euthyroid cats. Baseline group characteristics were compared to predict azotemic CKD. The influence of treatment on NAG_i was evaluated.
Results: Baseline NAG_i was significantly different among groups ( P = .004). Azotemic cats had a higher median value (13.12 U/g) when compared with healthy cats (1.38 U/g). With NAG_i >2.76 U/g, negative and positive predictive values for development of azotemia were 77.7 and 50%, whereas the combination of a urine specific gravity (USG) ≤1.035 and T₄ >7.80 μg/dL enhanced predictive values to 88.9 and 83.3%, respectively. NAG_i values decreased significantly over time in treated nonazotemic cats.
Conclusions and Clinical Relevance: Baseline NAG_i did not differentiate azotemic from nonazotemic euthyroid cats. NAG_i could be used to assess renal function during medical therapy allowing the clinician to adjust methimazole dosage accordingly. The combination of USG and T₄ could optimize identification of appropriate candidates for permanent treatment of hyperthyroidism.     

Effects of hyper‐ and hypothyroidism on the development and proliferation of testicular cells in prepubertal rats

Thyroid hormones are important in the development and regulation of testes. This study was conducted to determine the effects of hyper‐ and hypothyroidism on testicular development in prepubertal rats aged 20–70 days. Weaning male rats (20 days old) until day 70 age were randomly divided into four groups: control, hyperthyroid (hyper‐T), hypothyroid (hypo‐T) and hypothyroid treated with thyroxine (T4) (hypo‐T+T4). The results indicated that thyroid hormones caused a significant effect in body and testis weights, and food and water consumption. In addition there were changes in serum concentrations of tri‐iodothyronine, T4, thyroid stimulating hormone (TSH) and testosterone. Histomorphology showed a significant decrease in seminiferous tubule diameter in hyper‐T compared to the other groups. Leydig cell numbers showed a significant elevation in hyper‐T but not in hypo‐T groups. Immunostaining indicated that TSH receptor (TSHR), thyroid hormone receptors α/β (TRαβ) and proliferating cell nuclear antigen (PCNA) have the roles in testicular development. Our findings suggest that hyper‐ and hypo‐thyroidism regulate testicular cell proliferation and spermatogenesis in prepubertal rats, indicating that expression of TSHR, TRαβ and PCNA may be regulated by thyroid hormones that are involved in testicular development; and that the administration of T4 to the hypo‐T+T4 group leads to an improvement in the testicular condition.     

Effects of methimazole on renal function in cats with hyperthyroidism

The purpose of this study was to investigate the effects of methimazole on renal function in cats with hyperthyroidism. Twelve cats with naturally occurring hyperthyroidism and 10 clinically normal (i.e., control) cats were included in this study. All cats initially were evaluated with a history, physical examination, complete blood count, serum biochemistry profile, basal serum total thyroxine concentration, complete urinalysis, and urine bacterial culture. Glomerular filtration rate (GFR) was estimated by a plasma iohexol clearance (PIC) test. After initial evaluation, hyperthyroid cats were treated with methimazole until euthyroidism was achieved. Both groups of cats were then reevaluated by repeating the initial tests four to six weeks later. The mean (+/-standard deviation) pretreatment estimated GFR for the hyperthyroid cats was significantly higher (3.83+/-1.82 ml/kg per min) than that of the control cats (1.83+/-0.56 ml/kg per min). Control of the hyperthyroidism resulted in a significantly decreased mean GFR of 2.02+/-0.81 ml/kg per minute when compared to pretreatment values. In the hyperthyroid group, the mean increases in serum urea nitrogen (SUN) and creatinine concentrations and the mean decrease in the urine specific gravity after treatment were not statistically significant when compared to pretreatment values. Two of the 12 hyperthyroid cats developed abnormally high serum creatinine concentrations following treatment. These results provide evidence that cats with hyperthyroidism have increased GFR compared to normal cats, and that treatment of feline hyperthyroidism with methimazole results in decreased GFR.     

Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3'-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

OBJECTIVE: To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. ANIMALS: 24 dogs. PROCEDURE: Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. RESULTS: Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.     

Within- and between-examiner agreement for two thyroid palpation techniques in healthy and hyperthyroid cats

Thyroid gland palpation is an important aid for diagnosing feline hyperthyroidism in an early stage to prevent development of deleterious complications. Our objectives were to assess within- and between-examiner agreement for two thyroid gland palpation techniques in cats and to correlate palpation results with ultrasonographic thyroid measurements. Nine client-owned hyperthyroid (12.6 +/- 2.4 years) and 10 healthy control cats (7.4 +/- 5.4 years) entered this prospective study. Both thyroid glands of all cats were palpated twice by three blindfolded clinicians with the classic palpation technique [technique 1 (T1)] and the technique described by Norsworthy GD, Adams VJ, McElhaney MR, Milios JA [(2002a) Relationship between semi-quantitative thyroid palpation and total thyroxine concentration in cats with and without hyperthyroidism. Journal of Feline Medicine and Surgery 4, 139-143] [technique 2 (T2)]. A semi-quantitative score from 1 to 6 was assigned to the gland size. After clipping of the ventral cervical region, another palpation session followed by ultrasonography of the thyroid glands was performed. Average weighted kappa-values within- and between-examiners were 0.864 and 0.644 for T1 and 0.732 and 0.532 for T2. T1 did lead to significantly smaller within- (P=0.007) and between-examiner (P=0.048) differences than T2. Significant correlation coefficients (P<0.001) between the palpation scores of both techniques and ultrasonographic thyroid lobe length (T1: 0.43; T2: 0.38) were observed. No significant difference before and after clipping was found (T1: P=0.503; T2: P=0.607). The first time that all cats were palpated by either technique, significant score differences between control and hyperthyroid cats were observed both for T1 (P=0.002) and T2 (P=0.003). Both feline thyroid gland palpation techniques have good within- and between-examiner agreements. Based on this study, the classic palpation technique is preferred.     

Association of Iatrogenic Hypothyroidism with Azotemia and Reduced Survival Time in Cats Treated for Hyperthyroidism

Background: Iatrogenic hypothyroidism can occur after treatment of hyperthyroidism, and is correlated with a reduced glomerular filtration rate in humans and dogs. Hypothesis: Cats with iatrogenic hypothyroidism after treatment for hyperthyroidism will have a greater incidence of azotemia than euthyroid cats. Animals: Eighty client owned cats with hyperthyroidism. Methods: Two retrospective studies. (1) Longitudinal study of 12 hyperthyroid cats treated with radioiodine (documented as euthyroid after treatment), to assess changes in plasma thyroid stimulating hormone (TSH) concentration over a 6‐month follow‐up period, (2) Cross‐sectional study of 75 hyperthyroid cats (documented as euthyroid) 6 months after commencement of treatment for hyperthyroidism to identify the relationship between thyroid status and the development of azotemia. Kaplan‐Meier survival analysis was performed to identify relationships between thyroid and renal status and survival. Results: Plasma TSH concentrations were not suppressed in 7 of 8 cats with hypothyroidism 3 months after radioiodine treatment. The proportion of cats with azotemia was significantly (P= .028) greater in the hypothyroid (16 of 28) than the euthyroid group (14 of 47). Twenty‐eight of 41 cats (68%) with plasma TT4 concentration below the laboratory reference range had an increased plasma TSH concentration. Hypothyroid cats that developed azotemia within the follow‐up period had significantly (P= .018) shorter survival times (median survival time 456 days, range 231–1589 days) than those that remained nonazotemic (median survival time 905 days, range 316–1869 days). Conclusions and Clinical Importance: Iatrogenic hypothyroidism appears to contribute to the development of azotemia after treatment of hyperthyroidism, and reduced survival time in azotemic cats.     

THE EFFECT OF METHIMAZOLE ON THYROID UPTAKE OF PERTECHNETATE AND RADIOIODINE IN NORMAL CATS

Many hyperthyroid cats referred for thyroid imaging and 131I therapy are concurrently or recently receiving antithyroid medications. The effect of the antithyroid drug, methimazole, on thyroid uptake of 99mTcO4 and 123I was evaluated in 8 normal cats. Quantitative analysis was used to determine the normal percent dose uptake of 99mTcO4 and 123I, the change in thyroid:salivary ratios (T:S) of 99-TcO4 over time, and the duration of the methimazole effect on thyroid uptake of 123I. Methimazole was administered to 5 cats for 3 weeks in which a hypothyroid state was obtained; 3 cats served as non-treatment controls. 99mTcO4 and 8 and 24 hour 123I imaging was repeated after 3 weeks of methimazole therapy (time of maximum T4 suppression). Methimazole was then discontinued and 123I images and serum T4 concentrations were repeated at 1, 4, 9, 15, and 24 days post withdrawal. The percent dose uptake of 99mTcO4 increased throughout the acquisition period with maximum uptake occurring 4 hour post injection. The baseline 20 min. T:S ratio for controls and treatment cats were 0.79 +/- 0.08 and 0.81 +/- 0.05 respectively; with a peak value of 1.29 +/- 0.23 and 1.31 +/- 0.18 at 4 hours. The baseline T:S ratios were not significantly different from 20 minutes to 2 hours, however they were significantly elevated at 4 hours post injection. Baseline, 8 and 24 hour percent dose uptake of 123I were 2.1 +/- 0.42% and 7.04 +/- 1.24%, respectively. There was a significant increase in the T:S ratio in the treatment group at all time points. The 8 hour percent dose uptake of 123I at 1, 4, and 9 days post methimazole withdrawal were significantly increased and peaked at 4 days. The 24 hour uptake was significantly increased at 4 and 9 days, with peak uptake at 9 days post-methimazole withdrawal. The 123I percent dose uptake decreased to baseline values by day 15 post withdrawal. Radioiodine uptake is not inhibited by methimazole treatment in normal cats, and is significantly enhanced after recent withdrawal. This finding is supportive of a "short term rebund effect" with maximal enhanced uptake between 4 and 9 days after discontinuing antithyroid drugs. The increased uptake of 99mTcO4 may also affect the interpretation of 99mTcO4 thyroid scintigraphy for 2-3 weeks.