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.     

Best practice for the pharmacological management of hyperthyroid cats with antithyroid drugs

Pharmacological management of feline hyperthyroidism offers a practical treatment option for many hyperthyroid cats. Two drugs have been licensed for cats in the last decade: methimazole and its pro‐drug carbimazole. On the basis of current evidence and available tablet sizes, starting doses of 2·5 mg methimazole twice a day and 10 to 15 mg once a day for the sustained release formulation of carbimazole are recommended. These doses should then be titrated to effect in order to obtain circulating total thyroxine (TT4) concentrations in the lower half of the reference interval. Treated cases should be monitored for side‐effects, especially during the first months of treatment. Some side‐effects may require discontinuation of treatment. At each monitoring visit, clinical condition and quality of life should also be evaluated, with special attention to possible development of azotaemia, hypertension and iatrogenic hypothyroidism. When euthyroidism has been achieved, monitoring visits are recommended after 1 month, 3 months and biannually thereafter. Cats with pre‐existing azotaemia have shorter survival times. However, development of mild azotaemia during the initial course of treatment, unless associated with hypothyroidism, does not appear to decrease survival time. The long‐term effects of chronic medical management require further study .     

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

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

Clinical efficacy and safety of a once-daily formulation of carbimazole in cats with hyperthyroidism

O bjective : Evaluation of efficacy and safety of a novel controlled-release formulation of carbimazole in feline hyperthyroidism.
M ethods : A multicentre, self-controlled study in 44 client-owned cats with history and clinical signs of hyperthyroidism, and total thyroxine concentration greater than or equal to 50 nmol/l. Treatment was started at 15 mg once daily, response assessed after 10 days, and 3, 5, 8, 26 and 53 weeks and dose adjusted as required.
R esults : The median dose of carbimazole was 10 mg (range 10 to 15 mg) and 15 mg (5 to 25 mg) once daily after 3 and 53 weeks, respectively. Median total thyroxine concentration dropped significantly from 118 nmol/l (50 to 320 nmol/l) at presentation to 33 nmol/l (n=40) after 10 days, 31 nmol/l (n=34) at 3 weeks and 21 nmol/l (n=18) at 53 weeks. Clinical signs improved or resolved in almost all cats within three weeks after starting treatment. Twenty-one adverse reactions possibly (20) or probably (1) related to treatment were reported. During treatment, increased blood urea nitrogen concentration was observed in 25 per cent of the cats, eosinophilia in 20 per cent and lymphopenia in 16 per cent, while liver enzymes tended to improve.
C linical S ignificance : Once daily administration of controlled-release carbimazole tablets was effective and had expected tolerance in hyperthyroid cats during short- and long-term treatment.     

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.     

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.     

Agarose gel electrophoresis of alkaline phosphatase isoenzymes in the serum of hyperthyroid cats

Cats with hyperthyroidism [(increased serum thyroxine (T(4))] commonly have increased serum alkaline phosphatase (ALP) activity in addition to other serum biochemical abnormalities. Serum biochemical profiles were obtained from 10 hyperthyroid cats which had increased serum ALP. Agarose gel electrophoresis of serum from these cats was performed and stained for alkaline phosphatase activity. Alkaline phosphatase activity was calculated for each of the separate bands obtained, and the results were compared to those of tissue extracts, serum from normal cats, and serum from normothyroid cats with increased serum ALP activity. The hyperthyroid cats had increased ALP activity in bands corresponding to isoenzymes originating in the liver, bone, and an unidentified tissue source.     

Multiple myelomas in cats

Multiple myelomas are uncommon neoplasms of the bone marrow of cats [Weber NA, Tebeau CS (1998) An unusual presentation of multiple myeloma in two cats. Journal of the American Animal Hospital Association34 (6), 477-483]. Nine cats diagnosed with multiple myelomas were retrospectively identified over a 16-year period (1986-2002). Cats with multiple myelomas were older than 7 years (mean age 11.7 years); six males and three females were affected (2.1), but no breed predisposition was evident. Treatment of multiple myelomas consisted of supportive management in the nine cats and anti-neoplastic therapy in eight cats. Supportive treatment consisted of maintaining hydration, renal function and antimicrobial therapy even when there was no sign of infection. Anti-neoplastic therapy with melphalan and prednisolone was carried out in eight cats. Three failed to respond to treatment and five responded to treatment, but the response was only partial and temporary in one cat. The five cats that responded were improved clinically and had reduced serum protein levels. Five out of eight cats (63%) responded to chemotherapy, and it appeared to be complete in four cats and partial in one cat. Survival time in those cats was 15, 4, 17 and 24 months.     

Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998)

OBJECTIVE: To characterize clinical and clinicopathologic findings, response to treatment, and causes of systemic hypertension in cats with hypertensive retinopathy. DESIGN: Retrospective study. ANIMALS: 69 cats with hypertensive retinopathy. PROCEDURE: Medical records from cats with systemic hypertension and hypertensive retinopathy were reviewed. RESULTS: Most cats (68.1%) were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Cardiac abnormalities were detected in 37 cats, and neurologic signs were detected in 20 cats. Hypertension was diagnosed concurrently with chronic renal failure (n = 22), hyperthyroidism (5), diabetes mellitus (2), and hyperaldosteronism (1). A clearly identifiable cause for hypertension was not detected in 38 cats; 26 of these cats had mild azotemia, and 12 did not have renal abnormalities. Amlodipine decreased blood pressure in 31 of 32 cats and improved ocular signs in 18 of 26 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Primary hypertension in cats may be more common than currently recognized. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years). Amlodipine is an effective antihypertensive agent in cats.     

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.     

Hypertension in Cats With Chronic Renal Failure or Hyperthyroidism

The Doppler ultrasonic recording technique was used to measure systolic and diastolic blood pressures indirectly in 28 cats with naturally occurring renal failure, 39 cats with hyperthyroidism, and 33 clinically normal cats. The mean systolic and diastolic blood pressures in the normal cats were 118.4 +/- 10.6 mm Hg and 83.8 +/- 12.2 mm Hg, respectively. In the cats with chronic renal failure, both the systolic (146.6 +/- 25.4 mm Hg) and diastolic (96.6 +/- 15.2 mm Hg) blood pressures were significantly higher (P less than 0.0001 and P less than 0.01, respectively) than in the normal cats. Elevations in systolic and/or diastolic blood pressure were recorded in 17 (61%) of the 28 cats with chronic renal failure. In the 39 untreated hyperthyroid cats, both the mean systolic (167.9 +/- 28.9 mm Hg) and diastolic (111.6 +/- 21.5 mm Hg) pressures also were significantly higher (P less than 0.0001) than normal. Increased systolic and/or diastolic blood pressure was recorded in 34 (87%) of the 39 hyperthyroid cats. In seven cats with hyperthyroidism that were reevaluated two to four months after successful treatment of the hyperthyroid state, there was a significant fall in mean systolic pressure (P less than 0.05) from a pretreatment value of 159.5 +/- 15.4 mm Hg to a posttreatment value of 132.0 +/- 1.62 mm Hg. Overall, the results of this study indicate that mild to moderate hypertension is common in cats with chronic renal failure and in cats with untreated hyperthyroidism. In addition, the hypertension appears to be reversible following successful treatment of the hyperthyroid state.     

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.     

Association between urinary vascular endothelial growth factor excretion and chronic kidney disease in hyperthyroid cats

Many hyperthyroid cats develop azotaemic chronic kidney disease (aCKD) following treatment, which has led to the hypothesis that hyperthyroidism might be detrimental to renal function. Renin-angiotensin-aldosterone system (RAAS) activation occurs in hyperthyroidism, which could cause peri-tubular hypoxia, tubular damage and the development of aCKD. Urinary vascular endothelial growth factor:creatinine ratio (VEGFCR) is postulated to be a marker of tubular hypoxia. VEGFCR was correlated with plasma renin activity (PRA) and compared between hyperthyroid cats that did and did not develop aCKD following treatment (pre-azotaemic and non-azotaemic groups respectively). PRA was positively correlated with VEGFCR (r_s = 0.382; P = 0.028); however, pre-azotaemic hyperthyroid cats had significantly lower VEGFCR than non-azotaemic cats at baseline (median 122.3 fg/g versus 167.0 fg/g; P < 0.001). RAAS activation in hyperthyroidism is associated with increased VEGFCR; however, increased VEGFCR was not correlated with the development of aCKD. Therefore, tubular hypoxia may not be a mechanism for renal damage in hyperthyroid cats.     

Transdermal carbimazole for the treatment of feline hyperthyroidism

Orally administered antithyroid drugs are frequently used to treat hyperthyroidism in cats; however, the non-cooperative behaviour of some cats may make it difficult to administer tablets. The aim of this study was to develop a carbimazole ointment for application to the inner pinna of the ear and to test its effectiveness in 13 cats with hyperthyroidism. Laboratory investigations were performed before, and 4, 8, and 12 weeks after start of the treatment. Laboratory data for 9 cats were available at the end of the observation period. The starting dose of carbimazole ointment was 5 mg once daily. If no complications occurred, the dose was increased to 5 mg twice daily from the 6th day onwards. Further dose adjustments were mainly based on the plasma thyroxine (T4) concentration. The median plasma T4 concentration at the end of the observation period (24 nmol/l) was significantly lower than that before treatment (152 nmol/l). The dosage of carbimazole needed to achieve euthyroidism ranged from 4 to 17 mg twice daily. Treatment with carbimazole ointment resulted in disappearance of signs of hyperthyroidism; plasma concentrations of urea and creatinine increased significantly. The results of this study indicate that twice daily administration of carbimazole ointment to the inner pinna of the ear is an effective treatment for hyperthyroidism in cats. This provides the veterinarian with a new and promising treatment option. Because carbimazole ointment has not been registered, according to European law it can only be used for the treatment of hyperthyroidism in cats if other licensed medications have been tried and if there is a therapeutic need.     

Study of calcium homeostasis in feline hyperthyroidism

Thirty cats with untreated hyperthyroidism were blood sampled and their calcium homeosta-tic mechanisms and renal function assessed. The results were compared with those obtained from 38 age-matched control cats. The hyperthyroid group of cats were found to have significantly lower blood ionised calcium and plasma creatinine concentrations and significantly higher plasma phosphate and parathyroid hormone concentrations. Hyperparathyroidism occurred in 77 per cent of hyperthyroid cats, with parathyroid hormone concentrations reaching up to 19 times the upper limit of the normal range. The aetiology, significance and reversibility of hyperparathyroidism in feline hyperthyroidism remains to be established but could have important implications for both bone strength and renal function.     

Selenium status of cats in four regions of the world and comparison with reported incidence of hyperthyroidism in cats in those regions

OBJECTIVE: To assess selenium (Se) status of cats in 4 regions of the world and to compare results for Se status with reported incidence of hyperthyroidism in cats in those regions. ANIMALS: 50 cats (30 from 2 regions with an allegedly high incidence of hyperthyroidism and 20 from 2 regions in which the disease is less commonly reported). PROCEDURE: Hematologic samples (heparinized whole blood, plasma, and RBC fractions) were obtained from 43 healthy euthyroid cats and 7 hyperthyroid cats. Plasma concentration of Se and activity of glutathione peroxidase (GPX) in whole blood and plasma were determined. RESULTS: Plasma concentration of Se and GPX activity in whole blood or plasma did not differ significantly among cats from the 4 regions. However, cats had a plasma concentration of Se that was approximately 5 times the concentration reported in rats and humans. The GPX activity in whole blood or plasma in cats generally was higher than values reported in rats or humans. CONCLUSIONS AND CLINICAL RELEVANCE: Cats have higher Se concentrations in plasma, compared with values for other species. However, Se status alone does not appear to affect the incidence of hyperthyroidism in cats. High Se concentrations may have implications for health of cats if such concentrations are influenced by the amount of that micronutrient included in diets.     

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

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

Pharmacokinetics of controlled-release carbimazole tablets support once daily dosing in cats

Carbimazole, a prodrug of methimazole, is used in the treatment of hyperthyroidism in cats. The pharmacokinetics of methimazole was investigated in healthy cats following oral administration of 15 mg of carbimazole as a controlled-release tablet (Vidalta^®, Intervet). The controlled-release tablet did not produce a pronounced concentration peak and methimazole was present in the circulation for a sustained period, compared with a conventional tablet formulation. The time to reach peak concentrations after carbimazole administration was quite long (t_max 6 h). The absolute bioavailability of carbimazole was around 88 ± 11%. Repeated oral administration daily for 13 consecutive days did not lead to accumulation of methimazole in plasma. The extent of absorption of carbimazole was about 40% higher when administered to cats that had been fed compared to fasted cats. The relative oral bioavailability of methimazole following administration of the controlled-release tablets was similar to that of a conventional release formulation (83 ± 21%). The pharmacokinetics of this controlled-release formulation of carbimazole supports its use as a once daily treatment (both as a starting dose and for maintenance therapy) for cats with hyperthyroidism.