Adrenal function in cats with hyperthyroidism

Adrenal function may be altered in animals with hyperthyroidism. The aim of the study was to assess adrenal function of hyperthyroid cats (n = 17) compared to healthy cats (n = 18) and cats with chronic diseases (n = 18). Adrenal function was evaluated by adrenocorticotropic hormone (ACTH) stimulation test and the urinary cortisol to creatinine ratio (UCCR) was determined. Length and width of both adrenal glands were measured via ultrasound. Hyperthyroid cats had significantly higher cortisol levels before and after stimulation with ACTH than the other groups. However, the UCCR was not elevated in hyperthyroid cats. The size of the adrenal glands of hyperthyroid cats was not significantly different from the size of those of healthy cats. The results indicate that cats with hyperthyroidism have a higher cortisol secretory capacity in a hospital setting. The normal size of the adrenal glands suggests that cortisol levels may not be increased permanently.     

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)     

Echocardiographic findings in 103 cats with hyperthyroidism

Using M-mode echocardiography, cardiac abnormalities were studied in 103 cats with untreated hyperthyroidism. In addition, follow-up echocardiography was performed on 24 of these cats to assess the long-term (4 to 21 months) effect of treatment (thyroidectomy or radioiodine) on thyrotoxic cardiac disease. The most common echocardiographic abnormality in the 103 untreated hyperthyroid cats was hypertrophy of the left ventricular caudal wall (71.9%). Hypertrophy of the interventricular septum also was documented in 39.8% of the 103 cats. Other abnormalities included high values for left atrial diameter (70.0%), aortic root diameter (18.5%), and left ventricular diameter at end diastole (45.6%). In some of these cats, indices of contractility were enhanced; in 21.4% and 14.6% of the cats, values for shortening fraction and velocity of circumferential fiber shortening, respectively, were greater than those values measured in clinically normal cats. After treatment of the hyperthyroidism, left ventricular hypertrophy resolved or improved in many of the cats, as indicated by decreases in left ventricular caudal wall and interventricular septum thicknesses. Hyperdynamic wall motion resolved in all cats after treatment, as evidenced by consistent decreases in shortening fraction and velocity of circumferential fiber shortening. Despite these improvements, some cats had one or more persistently abnormal echocardiographic values after treatment. These results suggested that in cats, hyperthyroidism commonly is associated with largely reversible cardiomyopathy. In those cats in which cardiomyopathy persists or worsens after treatment, underlying primary cardiomyopathy or thyroid hormone-induced cardiac structural damage may exist.     

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.     

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.     

Prevalence of ocular abnormalities in cats with hyperthyroidism

The purpose of this study was to investigate the occurrence of ocular abnormalities in hyperthyroid cats. One hundred hyperthyroid cats and 30 clinically normal, geriatric cats were studied. In both groups, ophthalmic examination was performed by use of slit-lamp biomicroscopy and indirect ophthalmoscopy after application of 1% tropicamide to dilate the pupil. Ocular abnormalities were common in both the hyperthyroid and euthyroid cats. Approximately 75% of all eyes were affected with 1 or more abnormalities, and the range of abnormalities involved all structures of the eye. Significant differences between the euthyroid and hyperthyroid cats were found in the prevalence of prominent suture lines, nonpigmented deposits on the posterior lens capsule, hyperreflective ring around the optic nerve, and hyperpigmentation of the area centralis, but all of these abnormalities were more common in the euthyroid cats than in the cats with hyperthyroidism. Active retinal lesions were only observed in 3 hyperthyroid cats (3%). The results of this study indicate that hyperthyroidism does not seem to be a frequent cause of abnormalities in the eyes of cats.     

Congestive heart failure associated with hyperthyroidism in cats

Hyperthyroidism was diagnosed in 4 cats with congestive heart failure. Dyspnea and anorexia were observed in 3 of the 4 cats. In each cat, a holosystolic left and/or right apical heart murmur was auscultated. In 3 cats, a prominent extra heart sound (gallop rhythm) was auscultated. All cats had a palpably large thyroid lobe(s) and weight loss. The laboratory and ECG changes were similar to those reported for feline hyperthyroidism. Moderate-to-severe pleural effusion and cardiomegaly were detected via radiography in all cats. Some cats had radiographic signs of pulmonary venous engorgement and pulmonary edema. Echocardiography revealed cardiac dilatation and low left ventricular shortening fraction (wall motion) in all cats. Three cats responded initially to cardiac drugs and propylthiouracil or thyroidectomy. One of these died later, presumably from an adverse reaction to propylthiouracil, and the others died from recurrent congestive heart failure (1) or postoperative cardiac arrest (1). One cat did not respond to treatment, and died 2 days after diagnosis.     

Ultrasonographic measurements of adrenal glands in cats with hyperthyroidism

Feline hyperthyroidism is potentially associated with exaggerated responsiveness of the adrenal gland cortex. The adrenal glands of 23 hyperthyroid cats were examined ultrasonographically and compared to the adrenal glands of 30 control cats. Ten hyperthyroid cats had received antithyroid drugs until 2 weeks before sonography, the other 13 were untreated. There was no difference in adrenal gland shape between healthy and hyperthyroid cats: bean-shaped, well-defined, hypoechoic structures surrounded by a hyperechoic halo in 43/60 (71.6%) healthy cats and 34/46 (73.9%) hyperthyroid cats; more ovoid in 13/60 (21.6%) healthy cats and 9/46 (19.6%) hyperthyroid cats while more elongated in 4/60 (6.7%) healthy cats, 3/46 (6.5%) hyperthyroid cats. Hyperechoic foci were present in 9/23 (39.1%) hyperthyroid cats and 2/30 (6.7%) healthy cats. The adrenal glands were significantly larger in hyperthyroid cats, although there was overlap in size range. The mean difference between hyperthyroid cats and healthy cats was 1.6 and 1.7 mm in left and right adrenal gland length, 0.8 and 0.9 mm in left and right cranial adrenal gland height, and 0.4 and 0.9 mm in left and right caudal adrenal gland height. There was no significant difference between the adrenal gland measurements in treated and untreated hyperthyroid cats. The adrenomegaly was most likely associated with the hypersecretion of the adrenal cortex documented in hyperthyroid cats. Hyperthyroidism should be an alternative to hyperadrenocorticism, hyperaldosteronism, and acromegaly in cats with bilateral moderate adrenomegaly.     

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.     

Testing for hyperthyroidism in cats.

Hyperthyroidism remains a common endocrine disorder of cats. Although relatively easy to diagnose in classically presenting cats, the increased frequency of testing cats with early or mild disease has had significant implications for the diagnostic performance of many of the routine tests currently used. Further advances in the etiopathogenesis and earlier diagnosis are only likely with the advent of a species specific feline thyroid-stimulating hormone assay.     

Serum fructosamine concentration in cats with overt hyperthyroidism.

OBJECTIVE: To determine the effect of hyperthyroidism on serum fructosamine concentration in cats. DESIGN: Cohort study. ANIMALS: 22 cats with overt hyperthyroidism. PROCEDURE: Hyperthyroidism was diagnosed on the basis of clinical signs, detection of a palpable thyroid gland, and high total serum thyroxine (T4) concentrations. Hyperthyroid cats with abnormal serum albumin, total protein, and glucose concentrations were excluded from the study. Samples for determination of serum fructosamine concentration were obtained prior to initiating treatment. Results were compared with fructosamine concentrations in healthy cats, cats in which diabetes had recently been diagnosed, and cats with hypoproteinemia. In 6 cats, follow-up measurements were obtained 2 and 6 weeks after initiating treatment with carbimazole. RESULTS: Serum fructosamine concentrations ranged from 154 to 267 mumol/L (median, 198 mumol/L) and were significantly lower than values in healthy cats. Eleven (50%) of the hyperthyroid cats had serum fructosamine concentrations less than the reference range. Serum fructosamine concentrations in hyperthyroid, normoproteinemic cats did not differ from values in hypoproteinemic cats. During treatment, an increase in serum fructosamine concentration was detected. CONCLUSIONS AND CLINICAL RELEVANCE: In hyperthyroid cats, concentration of serum fructosamine may be low because of accelerated protein turnover, independent of blood glucose concentration. Serum fructosamine concentrations should not be evaluated in cats with overt hyperthyroidism and diabetes mellitus. Additionally, concentration of serum fructosamine in hyperthyroid cats should not be used to differentiate between diabetes mellitus and transitory stress-related hyperglycemia.     

Diagnostic tests for hyperthyroidism in cats

The diagnosis of hyperthyroidism, one of the most common disorders affecting elderly cats, is usually straightforward and considered routine by most practitioners. Nowadays, however, most cats suffering from hyperthyroidism tend to be diagnosed earlier and at a milder stage of the disease than those cats diagnosed 10 to 25 years ago. There are, in fact, a growing number of cats with clinical signs of hyperthyroidism and palpably large thyroid glands whose baseline serum total thyroid hormone concentrations are within the normal or borderline range, making diagnosis problematic. This paper reviews the available tests used to confirm a diagnosis of hyperthyroidism in cats and discusses their overall usefulness.     

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.     

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.     

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.     

High urinary corticoid/creatinine ratios in cats with hyperthyroidism

Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortisol secretion over a period of time. Therefore, this test is a very sensitive measure of adrenocortical function. The stress of the diagnostic procedure and nonadrenal disease may increase the urinary C : C ratio. In addition, diseases such as hyperthyroidism may influence the metabolic clearance of cortisol. To evaluate the effect of thyroid hormone excess, urinary C : C ratios were measured in 32 cats with hyperthyroidism and 45 healthy household cats. In 7 cats, urinary C : C ratios were measured both before and after treatment for hyperthyroidism. With data from the healthy cats, the reference range for the urinary C : C ratio was determined to be 8.0 to 42.0 X 10(-6). The urinary C : C ratios in the cats with hyperthyroidism (median, 37.5 x 10(-6); range, 5.9-169.5 x 10(-6)) were significantly (P = .001) higher than those in the healthy cats (median, 16 x 10(-6); range, 4.8-52.5 x 10(-6)). In 15 cats with hyperthyroidism, the urinary C : C ratios exceeded the upper limit of the reference range. Treatment for hyperthyroidism led to a marked decrease in urinary C : C ratios. The results of this study demonstrate that the urinary C : C ratio may be abnormally high in cats with hyperthyroidism, probably because of increased metabolic clearance of cortisol and activation of the pituitary-adrenocortical axis by disease. Although the clinical features of hyperthyroidism and hyperadrenocorticism in cats are different, hyperthyroidism should be ruled out when cats are suspected of hyperadrenocorticism on the basis of abnormally high urinary C : C ratios.     

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.     

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.     

Liver function in cats with hyperthyroidism before and after 131I therapy

BACKGROUND: The clinical significance of high serum concentration or activity of markers of liver damage in cats with hyperthyroidism is unknown. OBJECTIVE: To evaluate serum markers of liver function and damage, and ultrasonographic changes in cats with hyperthyroidism and with high liver enzymes, and to determine if abnormalities resolve after treatment with 131I. ANIMALS: Nineteen cats with hyperthyroidism (15 with high serum activities of liver enzymes) and 4 age-matched healthy control cats. METHODS: Serum bile acids, albumin, ammonia, cholesterol, and blood urea nitrogen concentrations, and activities of liver-derived enzymes, and blood glucose concentrations were measured before and after 131I therapy. These values were compared with those of cats that were euthyroid. In addition, gross liver parenchymal changes detected by abdominal ultrasonographic examination, before and after 131I therapy were evaluated. RESULTS: High serum liver enzyme activities were not associated with abnormalities in hepatic parenchyma and liver functional variables, regardless of the degree of increase. Serum liver enzyme activities return to normal after control of hyperthyroidism with 131I therapy. Cats with hyperthyroidism have a significantly higher serum fasting ammonia concentration than cats who were euthyroid (P = .019). Cats with hyperthyroidism also have significantly lower serum cholesterol (P = .005) and glucose (P = .002) concentrations before compared with after 131I therapy. Nine of 19 cats with hyperthyroidism had trace ketonuria. CONCLUSIONS AND CLINICAL IMPORTANCE: These results demonstrate that extensive examination for hepatobiliary disease in most cats with hyperthyroidism is unnecessary.