Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism

The objective of this study was to determine whether transdermal methimazole was as safe and effective as oral methimazole for the control of hyperthyroidism in cats. Forty-seven cats with newly diagnosed hyperthyroidism were randomized to receive either transdermal methimazole in pluronic lecithin organogel (PLO; applied to the inner pinna), or oral methimazole (2.5 mg q12h for either route). Cats were evaluated at weeks 0, 2, and 4 with a physical exam, body weight determination, CBC, biochemical panel, urinalysis, measurement of total levothyroxine (T4) concentration, indirect Doppler blood pressure determinaiton, and completion of an owner questionnaire. Data between the 2 groups and over time were compared by nonparametric methods. Forty-four cats followed the protocol (17 oral and 27 transdermal). Significantly more cats treated with oral methimazole had serum T4 concentrations within the reference range after 2 weeks (14 of 16 cats) compared to those treated by the transdermal route (14 of 25; P = .027). This difference was no longer significant by 4 weeks of treatment (9 of 11 for oral versus 14 of 21 for transdermal), possibly because of inadequate numbers evaluated by 4 weeks. Cats treated with oral methimazole had a higher incidence of gastrointestinal (GI) adverse effects (4 of 17 cats) compared to the cats treated with transdermal methimazole (1 of 27; P = .04), but no differences were found between groups in the incidence of neutropenia, hepatotoxicity, or facial excoriations. Although the overall efficacy of transdermal methimazole is not as high as that of oral methimazole at 2 weeks of treatment, it is associated with fewer GI adverse effects compared to the oral route.     

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.     

Triiodothyronine (T3) suppression test. An aid in the diagnosis of mild hyperthyroidism in cats

The purpose of this study was to develop a T3 suppression test to help in the diagnosis of mild hyperthyroidism in cats. We evaluated the response in circulating T4 concentrations to exogenous T3 (liothyronine) administration in 44 clinically normal cats, 77 cats with hyperthyroidism, and 22 cats with nonthyroidal disease. The test was performed by first collecting blood samples for basal serum T4 and T3 determinations, administering liothyronine at an oral dosage of 25 micrograms three times daily for seven doses, and, on the morning of the third day, again collecting serum samples for T4 and T3 determinations 2 to 4 hours after the seventh dose of liothyronine. The mean basal serum concentrations of T4 (53.1 nmol/L) and T3 (1.8 nmol/L) were significantly higher in the cats with hyperthyroidism than in the normal cats (T4 = 25.3 nmol/L, T3 = 1.3 nmol/L) and the cats with nonthyroidal disease (T4 = 29.5 nmol/L, T3 = 1.4 nmol/L); however, there was a great deal of overlap of basal values between the three groups of cats. Of the 77 cats with mild hyperthyroidism, 41 (53%) had serum T4 values and 55 (71%) had T3 values that were within the established normal ranges. After administration of liothyronine, mean serum T4 concentrations fell much more markedly in the normal cats and the cats with nonthyroidal disease than in the hyperthyroid cats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transdermal methimazole treatment in cats with hyperthyroidism

The objectives of this study were to assess serum thyroxine concentrations and clinical response in hyperthyroid cats to treatment with transdermal methimazole, and to determine if further investigation is indicated.Clinical and laboratory data from 13 cats with hyperthyroidism were retrospectively evaluated. Methimazole (Tapazole, Eli Lilly) was formulated in a pleuronic lecithin organogel (PLO)-based vehicle and was applied to the inner pinna of the ear at a dosage ranging from 2.5mg/cat q 24h to 10.0mg/cat q 12h. During the treatment period, cats were re-evaluated at a mean of 4.3 weeks (recheck-1), and again at a mean of 5.4 months (recheck-2).Clinical improvement was observed, and significant decreases in thyroxine concentrations were measured at recheck-1 (mean: 39.57nmol/L, SEM: 14.4, SD: 41.2) and recheck-2 (mean: 36.71nmol/L, SEM: 13.9, SD: 45.56) compared to pretreatment concentrations (mean: 97.5nmol/L, SEM: 11.42, SD: 39.5). No adverse effects were reported.     

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.     

Use of the triiodothyronine suppression test for diagnosis of hyperthyroidism in ill cats that have serum concentration of iodothyronines within normal range.

Administration of triiodothyronine (liothyronine, 15 micrograms, q 8 h, for 6 treatments) caused marked decrease in serum concentration of thyroxine (T4) and estimates of free T4 (fT4) concentration in clinically normal cats. A prospective clinical study was done to evaluate the use of this suppression test for diagnosis of hyperthyroidism in cats with clinical signs suggestive of the disease, but lacking high serum concentration of iodothyronines. Twenty-three cats were confirmed as hyperthyroid on the basis of histologic changes in the thyroid gland or clinical improvement in response to administration of methimazole. Mean +/- SD serum concentration of T4 (34.3 +/- 12.7 to 31.3 +/- 11.5 nmol/L) and estimate of fT4 concentration (26.6 +/- 6.4 to 25.6 +/- 6.9 pmol/L) did not change after administration of liothyronine to these cats. Twenty-three cats were classified as nonhyperthyroid by histologic confirmation of other disease, abnormal results of other diagnostic tests that strongly supported primary disease other than hyperthyroidism, or spontaneous remission of weight loss without treatment. Mean +/- SD serum concentration of T4 (27.9 +/- 10.3 to 11.7 +/- 6.4 nmol/L) and estimate of fT4 concentration (21.7 +/- 5.4 to 10.4 +/- 4.4 pmol/L) decreased significantly (P less than 0.001) in response to administration of liothyronine. Discriminant analysis was used to identify variables from iodothyronine assays (eg, absolute concentration of T4 or absolute estimate of fT4 concentration, or changes of T4 or fT4 concentration) that provided the best diagnostic sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988)

We reviewed the medical records of 494 cats with a variety of nonthyroidal diseases in which serum thyroxine (T4) concentration was determined as part of diagnostic evaluation. The cats were grouped by category of disease (ie, renal disease, congestive heart failure, diabetes mellitus, focal neoplasia, systemic neoplasia, hepatopathy, inflammatory bowel disease, inflammatory pulmonary disease, miscellaneous diseases, or undiagnosed disease), degree of illness (ie, mild, moderate, or severe), survival (ie, lived, died, or euthanatized), and presence or absence of a palpable thyroid gland. The mean (+/- SD) serum T4 concentrations in all 10 groups of cats, which ranged from 10.5 +/- 11.1 nmol/L in cats with diabetes mellitus to 18.7 +/- 7.8 nmol/L in cats with focal neoplasia, were significantly (P less than 0.001) lower than those of normal cats (27.0 +/- 10.4 nmol/L). The number of ill cats with low serum T4 concentrations (less than 10 nmol/L) was highest in the cats with diabetes mellitus (59%), hepatopathy (54%), renal failure (48%), and systemic neoplasia (41%). When the serum T4 concentrations in cats with mild, moderate, and severe illness were compared, mean concentrations were progressively lower (21.3 +/- 6.8, 14.8 +/- 8.1, and 6.5 +/- 5.8 nmol/L, respectively) as degree of illness increased. Severity of illness had a more significant (P less than 0.001) effect in lowering serum T4 concentrations than did disease category. Mean serum T4 concentrations in the cats that died (7.8 +/- 9.8 nmol/L) or were euthanatized (10.0 +/- 7.0 nmol/L) were also significantly (P less than 0.001) lower than those of cats that survived (15.2 +/- 8.8 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Pharmacologic management of feline hyperthyroidism.

Radioiodine is considered the treatment of choice for hyperthyroidism, but in some situations, methimazole therapy is preferred, such as in cats with preexisting renal insufficiency. Unfavorable outcomes from methimazole are usually attributable to side effects, such as gastrointestinal upset, facial excoriation, thrombocytopenia, neutropenia, or liver enzyme elevations. Because restoration of euthyroidism can lead to a drop in glomerular filtration rate, all cats treated with methimazole should be monitored with blood urea nitrogen and creatinine levels in addition to serum thyroxine (T(4)) and a complete blood cell count. Transdermal methimazole is associated with fewer gastrointestinal side effects and can be used in cats with simple vomiting or inappetence from oral methimazole. Hypertension may not resolve immediately when serum T(4) is normalized, and moderate to severe hypertension should be treated concurrently with atenolol, amlodipine, or an angiotensin-converting enzyme inhibitor.     

Methimazole Treatment of 262 Cats With Hyperthyroidism

The efficacy and safety of the antithyroid drug methimazole were evaluated over a 3-year period in 262 cats with hyperthyroidism. In 181 of the cats, methimazole was administered for 7 to 130 days (mean, 27.7 days) as a preoperative preparation for thyroidectomy. The remaining 81 cats were given methimazole for 30 to 1,000 days (mean, 228 days) as sole treatment for the hyperthyroid state. After 2 to 3 weeks of methimazole therapy (10 to 15 mg/d), the mean serum thyroxine (T4) concentration decreased significantly (P less than 0.001) from a pretreatment value of 12.1 micrograms/dl to 2.1 micrograms/dl. The final maintenance dose needed to maintain euthyroidism in the 81 cats that were given methimazole as sole treatment for hyperthyroidism ranged from 2.5 to 20 mg/d (mean, 11.9 mg/d). Clinical side effects developed in 48 (18.3%) cats (usually within the first month of therapy), which included anorexia, vomiting, lethargy, self-induced excoriation of the face and neck, bleeding diathesis, and icterus caused by hepatopathy. Mild hematologic abnormalities developed in 43 (16.4%) cats (usually within the first 2 months of treatment), which included eosinophilia, lymphocytosis, and slight leukopenia. In ten (3.8%) cats, more serious hematologic reactions developed including agranulocytosis and thrombocytopenia (associated with bleeding). These hematologic abnormalities resolved within 1 week after cessation of methimazole treatment. Immunologic abnormalities associated with methimazole treatment included the development of antinuclear antibodies in 52 of 238 (21.8%) cats tested and red cell autoantibodies (as evidenced by positive direct antiglobulin tests) in three of 160 (1.9%) cats tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of the Thyrotropin Releasing Hormone Stimulation Test to Diagnose Mild Hyperthyroidism in Cats

We evaluated serum T₄ and T₃ concentrations before and after administration of thyrotropin releasing hormone (TRH) in 35 cats with mild to moderate hyperthyroidism. 15 cats with nonthyroidal disease, and 31 clinically normal cats. The TRH stimulation test was performed by collecting blood for serum T₄ and T₃ determinations before and 4 hours after IV administration of 0.1 mg/kg TRH. Mean basal serum thyroid hormone concentrations in hyperthy-roid cats were significantly (P < .05) higher than concentrations in normal cats and in those with nonthyroidal disease, but there was considerable overlap among the 3 groups. After administration of TRH, mean serum T₄ concentrations increased significantly in all groups of cats, whereas mean T₃ concentrations increased significantly in normal cats and in those with nonthyroidal disease, but not in cats with hyperthyroidism. The absolute difference between mean basal and TRH-stimulated serum concentrations of T₄ in cats with hyperthyroidism (10.7 nmol/L) was significantly lower than the difference in the cats with nonthyroidal disease (20.0 nmol/L) and in clinically normal cats (28.3 nmol/L), but there was considerable overlap in values among groups. The mean value for relative change in serum T₄ concentration after TRH was significantly lower incats with hyperthyroidism (18.9%) than in those with nonthyroidal disease (110.0%) and in clinically normal cats (130.2%). Serum T₄ concentrations increased by > 50% in all normal cats and cats with nonthyroidal disease, whereas only 4(11.4%) of the 35 hyperthyroid cats had an increase of > 50% after TRH administration. On the basis of canonical discriminate analysis, the mean discriminant function score was significantly higher in the hyperthyroid cats (D = 63.8) than in cats with nonthyroidal disease (D = 5.9) or clinically normal cats (D = 0.7). All cats having a discriminant function score > 30 were hyperthyroid, whereas all cats with a value < 20 were euthyroid. Adverse side effects associated with administration of TRH were common and included transient vomiting, salivation, tachypnea, and defecation. Results of this study indicate that the TRH stimulation test is a useful aid in the diagnosis of hyperthyroidism in cats when basal serum T₄ concentrations are high-normal or only slightly high. As a diagnostic test, the TRH stimulation test compares favorably with the T₃ suppression test but requires less time and is more convenient to perform.     

The prevalence of hypocobalaminaemia in cats with spontaneous hyperthyroidism

Objectives : To determine the prevalence of hypocobalaminaemia in cats with moderate to severe hyperthyroidism and to investigate the relationship between cobalamin status and selected haematologic parameters. Methods : Serum cobalamin concentrations were measured in 76 spontaneously hyperthyroid cats [serum thyroxine (T₄) concentration ≥100 nmol/L] and 100 geriatric euthyroid cats. Erythrocyte and neutrophil counts in hyperthyroid cats with hypocobalaminaemia were compared with those in hyperthyroid cats with adequate serum cobalamin concentrations (≥290 ng/L). Results : The median cobalamin concentration in hyperthyroid cats was lower than the control group (409 versus 672 ng/L; P=0·0040). In addition, 40·8% of hyperthyroid cats had subnormal serum cobalamin concentrations compared with 25% of controls (P=0·0336). Weak negative correlation (coefficient: –0·3281) was demonstrated between serum cobalamin and T₄ concentrations in the hyperthyroid population, and the median cobalamin concentration was lower in cats with T₄ above the median of 153 nmol/L compared with cats with T₄ below this value (P=0·0281). Hypocobalaminaemia was not associated with neutropenia or anaemia in hyperthyroid cats. Clinical Significance : This study indicates that a substantial proportion of cats with T₄≥100 nmol/L are hypocobalaminaemic and suggests that hyperthyroidism directly or indirectly affects cobalamin uptake, excretion or utilisation in this species.     

Efficacy and safety of once versus twice daily administration of methimazole in cats with hyperthyroidism

OBJECTIVE: To determine whether once daily administration of methimazole was as effective and safe as twice daily administration in cats with hyperthyroidism. DESIGN: Randomized, nonblinded, clinical trial. ANIMALS: 40 cats with newly diagnosed hyperthyroidism. PROCEDURE: Cats were randomly assigned to receive 5 mg of methimazole, PO, once daily (n = 25) or 2.5 mg of methimazole, PO, twice daily (15). A complete physical examination, including measurement of body weight; CBC; serum biochemical analyses, including measurement of serum thyroxine concentration; and urinalysis were performed, and blood pressure was measured before and 2 and 4 weeks after initiation of treatment. RESULTS: Serum thyroxine concentration was significantly higher in cats given methimazole once daily, compared with cats given methimazole twice daily, 2 weeks (3.7 vs 2.0 micro +/- g/dL) and 4 weeks (3.2 vs 1.7 microg/dL) after initiation of treatment. In addition, the proportion of cats that were euthyroid after 2 weeks of treatment was lower for cats receiving methimazole once daily (54%) than for cats receiving methimazole twice daily (87%). Percentages of cats with adverse effects (primarily gastrointestinal tract upset and facial pruritus) were not significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that once daily administration of methimazole was not as effective as twice daily administration in cats with hyperthyroidism and cannot be recommended for routine use.     

Radioimmunoassay of serum total thyroxine and triiodothyronine in healthy cats: assay methodology and effects of age, sex, breed, heredity and environment.

Double antibody radioimmunoassays for thyroxine (T4) and triiodothyronine (T3) were established for use in cats, using standards in T4-and T3-free, normal cat serum. The assay working ranges were 5–200 nmol/1 for T4 and 0.125-10 nmol/1 for T3. Recovery of added hormone was 106 per cent ± 5.9 for T4 and 104 per cent ± 8.5 for T3 (mean ± 1 s.d.). Mean between-assay coefficients of variation (c.v.) were 6.6 per cent for T4 and 12–1 per cent for T3. Serum total T4 levels of 318 and total T3 levels of 299 healthy cats aged 4 months to 13 years were measured. Mean ± 1 s.d. values were 26.1 ± 10.1 nmol/1 for T4 and 0.69 ± 0.29 nmol/1 for T3. T4 and T3 concentrations within individual animals were highly correlated. T4 levels in both sexes tended to decrease until approximately 5 years of age and then rise again. A similar, though less pronounced effect, was found for T3, concentrations for older cats levelling out rather than rising. For any given age, females and neutered females tended to have significantly higher T4 values than males and neutered males, but such effects were not significant for T3. When other effects were accounted for, the effects of neutering were not significant for levels of either hormone. Pedigree animals tended to have higher levels of T3 at any given age than domestic short- and long-haired cats taken as one group. Animals living in the same environment had significantly similar T4 levels and T3 levels. For T3, this appeared to be due to a definite genetic component, but it was not possible to differentiate between environmental and genetic effects for T4.     

Tooth resorption and vitamin D3 status in cats fed premium dry diets

It has been suggested that tooth resorption (TR) in cats is associated with vitamin D3 status. The purpose of this study was to evaluate any correlation between serum 25-OH-D concentrations and the prevalence of TR. The healthy adult domestic cats (n=64) of this study had been fed similar premium dry-expanded foods throughout their lives. Serum 25-OH-D was measured, and cats received a single, complete periodontal examination, with periodontal probing of each tooth and exploration of the tooth surface using a dental explorer A complete set of 10 dental radiographs was taken for each cat. There were 168 TRs diagnosed in 40 of 64 cats (85 were Type 1 TR and 83 were Type 2). The mean serum 25-OH-D concentration was 187.7 +/- 87.3 nmol/L. The mean serum 25-OH-D in cats with one or more TR was 164.2 +/- 78.8 nmol/L, compared with 226.8 +/- 88.2 nmol/L for those without TR (p = 0.14). The mean serum 25-OH-D in the 13 cats with >5 TR was 131.2 +/- 49.5 nmol/L, which was significantly less than in cats with no TR (p < 0.05). There was no relationship between TR type and serum 25-OH-D. There was no effect of age or sex on serum 25-OH-D. On the contrary, variations in serum 25-OH-D were observed according to the studied breeds. There was no relationship between TR type and serum 25-OH-D. TR prevalence was greater in cats with lower serum 25-OH-D concentrations. In conclusion, the hypothesis that higher serum 25-OH-D concentrations are associated with a higher prevalence of TR is not supported by this study.     

Survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both: 167 cases (1996-2003)

OBJECTIVE: To compare survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both and identify factors associated with survival time. DESIGN: Retrospective case series. ANIMALS: 167 cats. PROCEDURE: Medical records of cats in which hyperthyroidism had been confirmed on the basis of high serum thyroxine concentration, results of thyroid scintigraphy, or both were reviewed. RESULTS: 55 (33%) cats were treated with 131I alone, 65 (39%) were treated with methimazole followed by 131I, and 47 (28%) were treated with methimazole alone. Twenty-four of 166 (14%) cats had preexisting renal disease, and 115 (69%) had preexisting hepatic disease. Age was positively correlated (r = 0.4) with survival time, with older cats more likely to live longer. Cats with preexisting renal disease had significantly shorter survival times than did cats without preexisting renal disease. When cats with preexisting renal disease were excluded, median survival time for cats treated with methimazole alone (2.0 years; interquartile range [IQR], 1 to 3.9 years) was significantly shorter than median survival time for cats treated with 131I alone (4.0 years; IQR, 3.0 to 4.8 years) or methimazole followed by 131I (5.3 years; IQR, 2.2 to 6.5 years). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that age, preexisting renal disease, and treatment type were associated with survival time in cats undergoing medical treatment of hyperthyroidism.     

PREDICTORS OF RESPONSE TO RADIOIODINE THERAPY IN HYPERTHYROID CATS

The objective of this retrospective study was to evaluate hyperthyroid cats for pretreatment factors that would predict response to radioiodine therapy. Hyperthyroidism was diagnosed in 193 cats based on elevated serum thyroxine levels and/or elevated thyroid to salivary gland ratios on thyroid scintigraphy. All cats were treated with an intravenous bolus of 4 mCi of radioiodine and follow-up serum thyroxine levels were evaluated at 1 week and 1, 3, 6, and 12 months post-therapy. There was a significant relationship between pretreatment thyroxine values and post-treatment thyroxine values at all of the follow-up time points (p < 0.001). There was also a relationship between thyroid to salivary gland technetium scan ratio results and serum thyroxine values at pretreatment and at 1 week post-treatment (p = 0.02, 0.005, respectively). A greater scan ratio was associated with higher thyroxine levels at these time points, but not at 1, 3, 6 or 12 months post-therapy. Ninety-eight cats pretreated with methimazole were analyzed for the effect of this drug on response to therapy. Methimazole was discontinued > or = 5 days before radioiodine therapy in 58 cats and < 5 days in 31 cats, in 9 cats the number of days off methimazole was unknown. There was no difference in response to radioiodine based upon when methimazole was discontinued (p = 0.70).     

Pharmacokinetics of selamectin following intravenous,oral and topical administration in cats and dogs

The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.     

Relationships between Low Serum Cobalamin Concentrations and Methlymalonic Acidemia in Cats

Background: Serum cobalamin concentrations below reference range are a common consequence of gastrointestinal disease in cats. Serum cobalamin ≤ 100 ng/L is associated with methylmalonic acidemia.
Objectives: To determine the prevalence of cobalamin deficiency, defined by elevated serum methylmalonic acid (MMA), in cats with serum cobalamin ≤ 290 ng/L, and the optimum serum cobalamin concentration to predict cobalamin deficiency in cats.
Sample Set: Residual serum samples (n = 206) from cats with serum cobalamin ≤ 290 ng/L.
Methods: Retrospective, observational study. Serum cobalamin and folate were measured with automated assays. Serum MMA was determined by gas chromatography-mass spectrometry. Cobalamin deficiency was defined as serum MMA > 867 nmol/L. Sensitivity and specificity of serum cobalamin concentrations ≤290 ng/L for detecting MMA > 867 nmol/L were analyzed using a receiver-operator characteristic curve.
Results: There was a negative correlation between serum cobalamin and MMA concentrations (Spearman's r =−0.74, P < 0.0001). The prevalence of MMA ≥ 867 nmol/L in cats with serum cobalamin ≤ 290 ng/L was 68.4%. Serum cobalamin ≤ 160 ng/L had a 74% sensitivity and 80% specificity for detecting MMA > 867 nmol/L. No significant difference in serum folate concentrations was detected between affected and unaffected cats.
Conclusions and Clinical Importance: Elevated MMA concentrations, suggesting cobalamin deficiency, are common in cats with serum cobalamin ≤ 290 ng/L. Cobalamin deficiency is clinically significant, and supplementation with parenteral cobalamin is recommended for cats with gastrointestinal disease and low serum cobalamin concentrations.     

Effect of Se on selenoprotein activity and thyroid hormone metabolism in beef and dairy cows and calves

Although Se is essential for antioxidant and thyroid hormone function, factors influencing its requirement are not well understood. A survey and two experiments were conducted to determine the influence of cattle breed and age on selenoprotein activity and the effect of maternal Se supplementation on cow and calf selenoprotein activity and neonatal thyroid hormone production. In our survey, four cowherds of different ages representing three breeds were bled to determine the influence of breed and age on erythrocyte glutathione peroxidase activity (RBC GPX-1). All females were nonlactating, pregnant, and consumed total mixed diets (Holstein) or grazed pasture (Angus and Hereford). In our survey of beef breeds, yearlings had greater average RBC GPX-1 activity than mature cows. In Exp. 1, neonatal Holstein heifers (n = 8) were bled daily from 0 to 6 d of age to determine thyroid hormone profile. An injection of Se and vitamin E (BO-SE) was given after the initial bleeding. Thyroxine (T4) and triiodothyronine (T3) concentrations were greatest on d 0 and decreased (P < 0.05) continuously until d 5 postpartum (156.13 to 65.88 and 6.69 to 1.95 nmol/L, d 0 to 5 for T4 and T3, respectively). Reverse T3 concentrations were 3.1 nmol/L on d 0 and decreased (P < 0.05) to 0.52 nmol/ L by d 5. In Exp. 2, multiparous Hereford cows were drenched weekly with either a placebo containing 10 mL of double-deionized H2O (n = 14) or 20 mg of Se as sodium selenite (n = 13). After 2 mo of treatment, Se-drenched cows had greater (P < 0.01) plasma concentrations than control cows (84.92 vs. 67.08 ng/mL), and at parturition, they had plasma Se concentrations twofold greater than (P < 0.05) control cows (95.51 vs. 47.14 ng Se/mL). After 4 mo, cows receiving Se had greater (P < 0.05) RBC GPX-1 activity than controls; this trend continued until parturition. Colostrum Se concentration was twofold greater (P < 0.05) in Se-drenched cows than control cows (169.97 vs. 87.00 ng/mL). Calves born to cows drenched with Se had greater (P < 0.05) plasma Se concentration, RBC GPX-1, and plasma glutathione peroxidase activity on d 0 compared with calves born to control cows. By d 7, no differences in plasma glutathione peroxidase activity in calves were observed. Maternal Se supplementation did not influence calf thyroid hormone concentrations. Selenium provided by salt and forages is not adequate for cattle in Se-deficient states.