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)     

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.     

Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease

OBJECTIVE: To determine the usefulness of measuring serum free thyroxine (T4) concentration as a diagnostic test for hyperthyroidism in cats, and to determine the influence of nonthyroidal disease on free T4 concentration in cats without hyperthyroidism. DESIGN: Prospective case series. ANIMALS: 917 cats with untreated hyperthyroidism, 221 cats with nonthyroidal disease, and 172 clinically normal cats. PROCEDURE: Serum free T4, total T4, and total triiodothyronine (T3) concentrations were measured in cats with untreated hyperthyroidism and cats with nonthyroidal disease. Serum total T4 and T3 concentrations were determined by use of radioimmunoassay, and free T4 concentration was measured by use of direct equilibrium dialysis. Reference ranges for hormone concentrations were established on the basis of results from the 172 clinically normal cats. RESULTS: Sensitivity of serum free T4 concentration as a diagnostic test for hyperthyroidism was significantly higher than the test sensitivity of either total T4 or T3 concentration. Of the 221 cats with nonthyroidal disease, 14 had a high free T4 concentration (ie, false-positive result). Therefore, calculated specificity of measuring serum free T4 concentration as a diagnostic test for hyperthyroidism was significantly lower than test specificity of measuring either the total T4 or T3 concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that determination of free T4 concentration is useful in the diagnosis of hyperthyroidism, especially in cats in which hyperthyroidism is suspected but total T4 and T3 concentrations are within reference ranges. However, because some cats with nonthyroidal disease have high serum free T4 concentrations, hyperthyroidism should not be diagnosed solely on the finding of high free T4 concentration.     

Evaluation of Serum Thyroid‐Stimulating Hormone Concentration as a Diagnostic Test for Hyperthyroidism in Cats

Background

In humans, measurement of serum thyroid‐stimulating hormone (TSH) concentration is commonly used as a first‐line discriminatory test of thyroid function. Recent reports indicate that canine TSH (cTSH) assays can be used to measure feline TSH and results can help diagnose or exclude hyperthyroidism.

Objectives

To investigate the usefulness of cTSH measurements as a diagnostic test for cats with hyperthyroidism.

Animals

Nine hundred and seventeen cats with untreated hyperthyroidism, 32 euthyroid cats suspected of having hyperthyroidism, and 131 clinically normal cats.

Methods

Prospective study. Cats referred to the Animal Endocrine Clinic for suspected hyperthyroidism were evaluated with serum T₄, T₃, free T₄ (fT ₄), and TSH concentrations. Thyroid scintigraphy was used as the gold standard to confirm or exclude hyperthyroidism.

Results

Median serum TSH concentration in the hyperthyroid cats (<0.03 ng/mL) was significantly (P < .001) lower than concentrations in clinically normal cats (0.05 ng/mL) or euthyroid cats with suspected thyroid disease (0.06 ng/mL). Only 18 (2.0%) hyperthyroid cats had measurable TSH concentrations (≥0.03 ng/mL), whereas 114 (69.9%) of the 163 euthyroid cats had detectable concentrations. Combining serum TSH with T₄ or fT ₄ concentrations lowered the test sensitivity of TSH from 98.0 to 97.0%, but markedly increased overall test specificity (from 69.9 to 98.8%).

Conclusions and Clinical Importance

Serum TSH concentrations are suppressed in 98% of hyperthyroid cats, but concentrations are measurable in a few cats with mild‐to‐moderate hyperthyroidism. Measurement of serum TSH represents a highly sensitive but poorly specific test for diagnosis of hyperthyroidism and is best measured in combination with T₄ and fT ₄.     

Radioactive iodine therapy for feline hyperthyroidism: Efficacy and administration routes

The efficacy of radioactive iodine (¹³¹I) administration was studied in a series of 50 hyperthy-roid cats. The dose administered to each cat was based on the clinical severity of the thyrotoxicosis, the serum total thyroxine (TJ concentration and the size of the goitre estimated by palpation. The activity ranged from 80 to 200 MBq (mean ± SD, 143 ± 24 MBq}. The ¹³¹I was injected intravenously in 27 cases and subcutaneously in 23 cases. Each cat was hospitalised for 30 days after the injection. Regardless of the route of injection, none of the cats exhibited any side effects after therapy and all tolerated the hospitalisation period well. There was a significant (P<0.001) decrease in the serum total T₄ concentration (reference range, 10.4 to 42.0 nmol/litre) from a mean ± SD of 181.3 ± 111.4 nmol/litre (range, 43.8 to 575.6 nmol/litre) to a mean ± SD of 19.0 ± 29.6 nmol/litre (range, 2.0 to 175.7 nmol/litre) 30 days following the injection of the radioisotope. Five cats remained hyperthyroid, although in each case the serum total T₄ concentrations had decreased from pre-treatment values. Two of the cats subsequently became euthyroid within three and five months of therapy, respectively, two were lost to adequate follow-up and the remaining cat was successfully retreated four months later. Before treatment, four of these cases had high scores based on the three criteria used for dose estimation. Serum total T₄ concentrations below the reference range developed after treatment in many cases, but were often transient. Clinical evidence of hypothyroidism was not apparent in any cat. Recurrence of hyperthyroidism has not occurred in follow-up periods of up to 32 months. There was no difference in the outcome between the cats injected intravenously or subcutaneously and the latter was considered to be safer and simpler. The administration of an approximated dose of ¹³¹I proved to be an effective treatment for hyperthyroidism in 47 (94.0 per cent) of the cats and obviated the need for sophisticated nuclear computer facilities. There may be a lag period in some cases before euthy-roidism is achieved and this should be considered before the administration of a second dose. ¹³¹I can be administered subcutaneously without untoward effects.     

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)     

EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID‐TO‐SALIVARY RATIO AND THYROID‐TO‐BACKGROUND RATIOS

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid‐to‐salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid‐to‐background ratios (T/B) or percent thyroidal uptake of ^99mTcO^?₄ (TcTU) has only been reported in a few studies. The purpose of this prospective, cross‐sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T₄), triiodothyronine (T₃), free T₄ (fT₄), and thyroid‐stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T₄ (r = 0.76 vs. 0.64), T₃ (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland.     

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.     

Carbimazole therapy of feline hyperthyroidism

The efficacy and safety of carbimazole (CBZ) was studied in a series of 45 hyperthyroid cats. CBZ was used before surgical thyroidectomy in 34 cats, at a dose of 5 mg administered orally every eight hours. Biochemical euthyroidism, as assessed by a decrease in serum total thyroxine (T₄) concentrations into the reference range, was achieved in 31 cats (91 per cent) within a mean (± SD) of 5–7 (± 2–9) days (range, three to 15 days). Clinical evidence of euthyroidism tended to lag behind biochemical evidence but was usually apparent after 14 days. Continuing therapy tended to decrease serum total T₄ but not serum total triiodothyronine (T₃) concentrations below the reference range but clinical evidence of hypothyroidism was not apparent. In five additional cats, 5 mg CBZ was administered three times between 08.00 and 20.00 hours. Euthyroidism was achieved in only one cat after 14 days, emphasising the need for eight hourly dosing. Clinically observable side effects developed in five cats (13 per cent), two to three weeks after commencing therapy and included vomiting (n y 2) and vomiting and anorexia (n = 3). In three cases withdrawal of CBZ was required. Mild and transient haematological abnormalities developed in two cats (one case each of lymphocytosis and leucopenia). There were significant decreases in serum concentrations of alanine aminotransferase and alkaline phosphatase in those cats achieving euthyroidism (P < 0–001 in each case) but not in those that remained hyperthyroid despite CBZ therapy (P ± 0–05 in each case). CBZ was used as the sole therapy for the condition in eight cats for between four and 65 weeks. A consistent dosage of 5 mg CBZ administered twice daily was necessary to maintain euthyroidism. Adverse reactions were not noted. Chronic medical management tended to depress serum total T₄ concentrations below the reference range. Corresponding serum total T₃ concentrations remained within the reference range on 15 (88 per cent) of 17 occasions and may explain why the animals appeared clinically euthyroid. CBZ appears to be a safe and effective drug both in the short and long term management of feline hyperthyroidism and can be recommended as the current drug of choice in the UK.     

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)     

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.     

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.     

Diagnosis of hyperthyroidism in cats with mild chronic kidney disease

OBJECTIVES: In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. METHODS: Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (>8 years) cats. RESULTS: In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (> or =40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. CLINICAL SIGNIFICANCE: The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease.     

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)     

Serum Thyroid Hormone Concentrations Fluctuate in Cats with Hyperthyroidism

We measured serum thyroxine (T4) and 3,3',5-triiodothyronine (T3) concentrations in hyperthyroid cats (hourly for 10 hours in 14 cats, and daily for 15 days in seven cats) to assess fluctuation in thyroid hormone levels. Over the 10-hour study period the coefficient of variation (CV) for serum T4 and T3 concentrations ranged from 6.4-22.6% (mean = 12.0 +/- 4.8%) and from 9.6-33.1% (mean = 17.5 +/- 6.3%), respectively. During the 15-day study period, CV for serum T4 ranged from 6.6-34.8% (mean = 18.4 +/- 9.3%), while CV for serum T3 ranged from 7.8-31.0% (mean = 20.1 +/- 8.6%). These CV values were significantly higher than the expected intra-assay CVs (T4 assay, 5.1%; T3 assay, 7.7%). In addition, some of the cats with mild hyperthyroidism showed one or more normal serum T4 and T3 values during the course of the respective study periods. There was no specific time during the 10-hour study period at which the cats consistently showed peak serum T4 or T3 concentrations. These results suggest that serum thyroid hormone concentrations are subject to a degree of fluctuation that exceeds the usual assay variation, and that cats with mild hyperthyroidism can, at a given time, exhibit normal serum T4 and T3 values. Therefore, a diagnosis of feline hyperthyroidism should not be excluded on the basis of the finding of a single normal serum T4 or T3 value in a cat with clinical signs and physical examination findings consistent with the disease.     

Altered disposition of propylthiouracil in cats with hyperthyroidism

The oral and intravenous disposition of the anti-thyroid drug propylthiouracil (PTU) was determined in six clinically healthy cats and four cats with naturally occurring hyperthyroidism. Compared with the normal cats, the mean plasma elimination half-life of PTU was significantly (P less than 0.001) shorter in the hyperthyroid cats (77.5 +/- 5.8 minutes compared with 125.5 +/- 3.7 minutes) and the total body clearance of PTU was significantly (P less than 0.05) more rapid in the cats with hyperthyroidism (5.1 +/- 0.8 ml kg-1 min-1 compared with 2.7 +/- 0.2 ml kg-1 min-1). Following oral administration, both the bioavailability (59.7 +/- 4.9 per cent compared with 73.3 +/- 3.7 per cent) and peak plasma concentrations (14.5 +/- 1.6 micrograms ml-1 compared with 18.9 +/- 0.9 micrograms ml-1) of PTU were significantly (P less than 0.05) lower in the hyperthyroid cats than in the control cats. No difference was noted, however, between the apparent volume of distribution for PTU in the two groups of cats. Overall, results of this study indicate that the oral bioavailability of PTU is decreased and PTU disposition is accelerated in cats with hyperthyroidism.     

Serum thyroxine concentrations after radioactive iodine therapy in cats with hyperthyroidism

Thirty-one cats with hyperthyroidism were given one dose of radioactive iodine (131I) IV. Serum thyroxine (T4) concentrations were measured before treatment in all cats, at 12-hour intervals after treatment in 10 cats, and at 48-hour intervals after treatment in 21 cats. Serum T4 concentrations also were measured one month after 131I therapy in 29 cats. Activity of 131I administered was 1.5 to 6.13 mCi, resulting in a dose of 20,000 rads to the thyroid. Serum T4 concentrations before 131I administration were 5.3 to 51.0 micrograms/dl, with a median T4 concentration of 11.0 micrograms/dl. Serum T4 decreased most rapidly during the first 3 to 6 days after treatment. Sixteen cats (55%) had normal serum thyroxine concentrations by day 4 after 131I administration, and 23 cats (74%) were euthyroxinemic by day 8 after treatment. One month after administration of 131I, the 29 cats evaluated were clinically improved, and 24 (83%) of the 29 cats evaluated had normal serum T4 concentrations, 3 cats (10%) remained hyperthyroxinemic, and 2 cats (7%) were hypothyroxinemic. Therefore, administration of 131I was a safe and effective method to quickly decrease serum T4 concentrations in hyperthyroid cats.     

Glucose tolerance and insulin secretion in spontaneously hyperthyroid cats

Glucose tolerance and insulin secretion after administration of a glucose load were determined in 11 clinically normal cats and 15 cats with spontaneous hyperthyroidism. In six hyperthyroid cats, a glucose tolerance test was repeated after treatment with radioactive iodine (131I). All cats had similar baseline glucose concentrations. However, the cats with hyperthyroidism had a significantly decreased glucose clearance, which was worse after treatment. Hyperthyroidism also caused a marked increase in basal and glucose-stimulated insulin secretion, which was not improved with treatment. It is concluded that hyperthyroidism in cats may lead to long-lasting alterations of glucose tolerance and insulin secretion which may not be reversed by treatment.     

Effect of clomipramine on the electrocardiogram and serum thyroid concentrations of healthy cats

Clomipramine is a tricyclic antidepressant (TCA) commonly used to treat anxiety related behavioral disorders in companion animals. Tricyclic antidepressants (TCAs) have the potential to cause arrhythmias in humans and companion animals. The effect of the TCAs, clomipramine, and amitriptyline, at therapeutic dosages on cardiac rhythm has been evaluated in dogs. The effect of clomipramine on the cardiac rhythm of cats has not been reported. In Experiment 1, 7 healthy cats were selected to evaluate the effect of clomipramine on their cardiac rhythm using an electrocardiogram. A baseline electrocardiogram was carried out before (Day 0) and repeated (Day 29) after 4 weeks (28 days) of daily clomipramine (10 mg/cat PO) administration. Significant changes in the electrocardiogram were not found after 28 days of daily clomipramine administration. In Experiment 2, 7 healthy cats were enrolled in the study to evaluate the effect of clomipramine administration on the serum thyroid concentrations in cats. Clomipramine (10 mg/cat PO daily) was administered to all cats beginning on Day 1, and continued for 28 days. Serum total thyroxine (T₄), triiodothyronine (T₃), and free thyroxine (fT₄) concentrations were measured before (Day 0) and repeated (Day 29) after 4 weeks (28 days) of daily clomipramine administration. Statistically significant decreases in serum thyroid concentrations (T_4, T₃, and fT₄) were noted between pre and post clomipramine administration. A decrease of 25, 24, and 16% in serum T₄, T₃, and fT₄ concentrations, respectively, may lead to a misdiagnosis of euthyroidism in a subclinical hyperthyroid patient. A longer duration of drug treatment might further suppress thyroid function when used as a single agent, with concomitantly administered drugs, or in conjunction with euthyroid sick syndrome.     

Hypertropic cardiomyopathy and hyperthyroidism in the cat

In a 21/2-year period, hypertrophic cardiomyopathy was found at necropsy of 23 cats that died (13 cats) or were euthanatized (10) because of problems associated with hyperthyroidism. Of these, 4 (17%) also had evidence of cardiac failure (pulmonary edema or pleural effusion). The mean body weight of the cats with hyperthyroidism and hypertrophic cardiomyopathy was significantly less (P less than 0.001) than that of clinically normal cats and cats with primary cardiomyopathy (congestive or restrictive) or excessive moderator band cardiomyopathy. In addition, the ratio of heart weight to body weight was significantly greater (P less than 0.001) in the 23 hyperthyroid cats than in the normal cats and cats with primary cardiomyopathy. Twenty (87%) of the cats had symmetric hypertrophy of the ventricular septum and left ventricular free wall, whereas the remaining 3 cats had disproportionate thickening of the ventricular septum, compared with the free wall, similar to what is found in cats with asymmetric hypertrophic cardiomyopathy. Histologic cardiac abnormalities included large, hyperchromatic nuclei, interstitial fibrosis, endocardial fibroplasia, fibrosis of the atrioventricular node, and marked disorganization of cardiac muscle cells. The study showed that hypertrophic cardiomyopathy develops in most hyperthyroid cats, some of which also develop congestive heart failure. Although the signs of heart disease in primary myocardial disease and thyrotoxic disease are similar, the characteristic signalment and clinical signs of hyperthyroidism should lead one to suspect the association of hypertrophic cardiomyopathy with the hyperthyroidism.