Antioxidant status in hyperthyroid cats before and after radioiodine treatment

Background

Reversible antioxidant depletion is found in hyperthyroid humans, and antioxidant depletion increases the risk of methimazole toxicosis in rats.

Objectives

To determine whether abnormalities in concentrations of blood antioxidants or urinary isoprostanes were present in hyperthyroid cats, and were reversible after radioiodine treatment. To determine whether or not antioxidant abnormalities were associated with idiosyncratic methimazole toxicosis.

Animals

Hyperthyroid cats presented for radioiodine treatment (n = 44) and healthy mature adult control cats (n = 37).

Methods

Prospective, controlled, observational study. Red blood cell glutathione (GSH), plasma ascorbate (AA), plasma free retinol (vitamin A), α‐tocopherol (vitamin E), and urinary free 8‐isoprostanes in hyperthyroid cats were compared to healthy cats and to hyperthyroid cats 2 months after treatment.

Results

Blood antioxidants were not significantly different in hyperthyroid cats (mean GSH 1.6 ± 0.3 mM; AA 12.8 ± 4.9 μM, and vitamin E, 25 ± 14 μg/mL) compared to controls (GSH 1.4 ± 0.4 mM; AA 15.0 ± 6.6 μM, and vitamin E, 25 ± 17 μg/mL). Urinary isoprostanes were increased in hyperthyroid cats (292 ± 211 pg/mg creatinine) compared to controls (169 ± 82 pg/mg; P = .006), particularly in hyperthyroid cats with a USG < 1.035. Plasma free vitamin A was higher in hyperthyroid cats (0.54 ± 0.28 μg/mL versus 0.38 ± 0.21 in controls; P = .007). Both abnormalities normalized after radioiodine treatment. No association was found between oxidative status and prior idiosyncratic methimazole toxicosis.

Conclusion and Clinical Importance

Increased urinary isoprostane could reflect reversible renal oxidative stress induced by hyperthyroidism, and this requires additional evaluation.     

Plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol in hyperthyroid cats before and after treatment with radioiodine

BACKGROUND: Glomerular filtration rate (GFR) can be measured by clearance methods of different markers showing discrepancies and different reproducibility in healthy cats. Studies comparing different methods of GFR measurement in hyperthyroid cats have not yet been performed. HYPOTHESIS: Plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), and endo-iohexol (PenICT) could lead to differences in GFR measurement and the need to use the same clearance method when comparing GFR before and after radioiodine treatment in hyperthyroid cats. ANIMALS: Fifteen client-owned hyperthyroid cats. METHODS: GFR was measured 1 day before and 1, 4, 12, and 24 weeks after treatment. Intravenous injection of iohexol was followed immediately by IV injection of creatinine. Plasma creatinine was measured by an enzymatic method. Plasma endo- and exo-iohexol were measured by high-performance liquid chromatography coupled to ultraviolet detection. RESULTS: Globally, the 3 GFR methods resulted in significantly different (P < .001) GFR results. GFR results among the different methods were the same (P= .999) at all time points. All 3 techniques indicated decreasing GFR after (131)I treatment. For each GFR technique, a significant decrease in GFR was observed between time point 0 and all other time points. This decrease stabilized 4 weeks after treatment, with very little decline afterward. CONCLUSION AND CLINICAL IMPORTANCE: It is mandatory to use the same GFR technique in follow-up studies. GFR testing at 4 weeks posttreatment could allow assessment of the final renal functional loss after treatment in hyperthyroid cats.     

Prothrombin, activated partial thromboplastin, and proteins induced by vitamin K absence or antagonists clotting times in 20 hyperthyroid cats before and after methimazole treatment

The effect of daily doses of 5-15 mg of methimazole on the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and proteins induced by vitamin K absence or antagonists (PIVKA) clotting time in 20 hyperthyroid cats was determined. No significant (P > .05) difference was found in median platelet count. PT, APTT, or PIVKA clotting time before treatment compared to median values at 2-6 weeks or > or =7-12 weeks of methimazole treatment. No cat had a prolonged APTT at any time. At 2-6 weeks of methimazole treatment, 1 cat each developed thrombocytopenia or prolonged PIVKA clotting time despite initially normal values. Three cats had abnormal coagulation tests (prolonged PT [n = 1] and PIVKA clotting time [n = 3]) before treatment that fluctuated during treatment. Excluding the 3 cats that had abnormal PIVKA clotting time before treatment, prolonged PIVKA clotting time developed in 6% (1/17; 95% confidence interval, 0-28%) cats treated with methimazole for 2-6 weeks. Seemingly. doses of methimazole commonly used to treat hyperthyroidism in cats do not cause alteration in PT and APTT, and only rarely prolong PIVKA clotting time. Nevertheless, abnormal PIVKA clotting time may explain bleeding tendencies unassociated with thrombocytopenia in methimazole-treated hyperthyroid cats.     

Urinary Markers in Healthy Young and Aged Dogs and Dogs with Chronic Kidney Disease

Background: Blood urea nitrogen and serum creatinine concentrations only detect a decrease of >75% of renal functional mass. Therefore, there is a need for markers that allow early detection and localization of renal damage.
Hypothesis: Urinary albumin (uALB), C-reactive protein (uCRP), retinol binding protein (uRBP), and N -acetyl-β- d -glucosaminidase (uNAG) concentrations are increased in dogs with chronic kidney disease (CKD) compared with healthy controls and in healthy older dogs compared with young dogs.
Animals: Ten dogs with CKD, 10 healthy young dogs (age 1–3 years), and 10 healthy older dogs (age > 7 years) without clinically relevant abnormalities on physical examination, hematology, biochemistry, and urinalysis.
Methods: Urinary markers were determined using an ELISA (uALB, uCRP, and uRBP) or a colorimetric test (uNAG). Results were related to urinary creatinine (c). The fixed effects model or the Wilcoxon rank sum test were used to compare the different groups of dogs.
Results: uALB/c, uRBP/c, and uNAG/c were significantly higher in CKD dogs than in healthy dogs. No significant difference was found for uCRP, which was not detectable in the healthy dogs and only in 3 of the CKD dogs. Between the healthy young and older dogs, no significant difference was detected for any of the markers.
Conclusion: The urinary markers uALB/c, uRBP/c, and uNAG/c were significantly increased in dogs with CKD compared with healthy controls. Additional studies are needed to evaluate the ability of these markers to detect renal disease before the onset of azotemia.     

Recombinant human thyrotropin administration enhances thyroid uptake of radioactive iodine in hyperthyroid cats

BACKGROUND: Hyperthyroidism is the most diagnosed endocrine disorder in cats and radioiodine (131I) is the treatment of choice. The dose emission rate and radioactivity in urine, saliva, and on hair and paws are determined by the dose of administered 131I. A dose reduction of therapeutic 131I could possibly be achieved after recombinant human thyrotropin (rhTSH) administration as in humans with nodular goiter. HYPOTHESIS: rhTSH will increase radioiodine uptake in hyperthyroid cats. ANIMALS: Five hyperthyroid cats. METHODS: Twenty-five micrograms rhTSH (day 1) or 2 mL 0.9% sodium chloride (NaCl) (day 9) was injected IV. One hour later, 11.4 +/- 4.1 (mean +/- SD) MBq 123I was injected IV. Radioactive iodine uptake (RAIU) was measured 6, 12, and 24 hours after rhTSH (RAIU-rhTSH) or NaCl (RAIU-blanco) injection. Blood samples for measurement of TT4 were taken before injection of rhTSH or NaCl (TT4(0)) and at the time of imaging. RESULTS: Percentages of RAIU-rhTSH (and RAIU-blanco) at 6, 12, and 24 hours after administration of rhTSH were 34 +/- 18 (31 +/- 21), 46 +/- 20 (38 +/- 18), and 47 +/- 15 (36 +/- 14). There was a statistically significant effect of rhTSH administration on RAIU (P = .043) but not on serum TT4 concentration. Baseline serum TT4(0) concentration influenced RAIU-rhTSH significantly at 6 hours (P = .037). CONCLUSION AND CLINICAL IMPORTANCE: The increased RAIU observed after rhTSH administration in hyperthyroid cats could lead to a lower therapeutic dose of 131I after rhTSH administration in hyperthyroid cats and decreased risk of environmental and owner contamination during and after hospitalization.     

Escherichia coli pyometra induces transient glomerular and tubular dysfunction in dogs

Background: Pyometra in dogs has been associated with renal injury. Hypothesis: Examine pyometra‐related nephropathy by evaluating novel renal biomarkers. Animals: Twenty‐five dogs with Escherichia coli pyometra. Fourteen clinically healthy bitches of comparable age. Methods: Prospective study. Urinary biomarkers determined by immunoassays (uIgG, uCRP, uAlb, uRBP, uTXB₂) or colorimetric test (uNAG) with results normalized to urine creatinine concentration. Nonparametric Mann‐Whitney U‐test and Wilcoxon's signed‐rank test used to compare healthy dogs and dogs with pyometra, and dogs with pyometra at initial and follow‐up examination. Results: Urinary biomarkers (median, range) significantly increased in dogs with pyometra (uIgG/Cr: 169.7 mg/g, 4.8–1052.9; uCRP/Cr: 0.260 mg/g, 0.006–3.030; uAlb/Cr: 89.5 mg/g, 8.8–832.7; uRBP/Cr: 1.66 mg/g, 0.05–21.44; uNAG/Cr: 5.8 U/g, 1.6–27.7; uTXB₂/Cr: 15.3 μg/g, 3.2–139.6) compared with healthy bitches (uIgG/Cr: 3.4 mg/g, 0.6–8.9; uCRP/Cr: below detection limit; uAlb/Cr: 17.5 mg/g, 1.3–166.3; uRBP/Cr: 0.13 mg/g, 0.02–0.44; uNAG/Cr: 2.4 U/g, 1.4–7.4; uTXB₂/Cr: 2.4 μg/g, 1.2–4.7) (P < .001). Six months after ovariohysterectomy, urinary biomarkers in pyometra group (uIgG/Cr: 4.7 mg/g, 1.5–99.8; uCRP/Cr: below detection limit; uAlb/Cr: 13.9 mg/g, 2.1–471.2; uRBP/Cr: 0.05 mg/g, 0.02–0.32; uNAG/Cr: 1.6 U/g, 0.9–3.3; uTXB₂/Cr: 3.3 μg/g, 1.0–6.9) were significantly lower than before surgery (P < .01), and not significantly different to those of healthy dogs (P > .05). Conclusion and Clinical Importance: Pyometra‐related renal dysfunction affects the nephron both at glomerular and proximal tubular level and is a transient process in most dogs with E. coli pyometra.     

Long-term health and predictors of survival for hyperthyroid cats treated with iodine 131

Two hundred thirty-one cats treated with radioactive iodine at the Texas Veterinary Medical Teaching Hospital were followed for a median of 25 months by means of an ambidirectional (prospective, retrospective) cohort study design. Cox proportional hazards models were used to determine predictors of survival based on data at the time of hyperthyroid diagnosis (collected retrospectively) and found that only age at diagnosis and sex of the cat were predictors of survival. Increasing age (for each year of age, relative risk [RR] = 1.2, 95% confidence interval [CI] = 1.1-1.3) and being male (RR = 0.68, 95% CI = 0.5-0.9) increased likelihood of death. Tables predicting survival after diagnosis and treatment of hyperthyroidism for various age and sex combinations were created. In addition, Cox proportional hazard models were run with all data available at the end of the study (collected retrospectively and prospectively) including number and type of major health problems reported at the time of death or censoring. In this model, significant factors were age at diagnosis, sex, and either type of major health problem or number of health problems. Cats with renal disease or cancer were more likely not to survive and increasing from none to 2 health problems also decreased survival. Renal problems and cancer were the most common health problems at the time of death or censoring. This study provides estimates of duration of survival for cats successfully treated for hyperthyroidism with radioactive iodine, which can be useful in assisting with client treatment decisions.     

Serum troponin I levels in hyperthyroid cats before and after treatment with radioactive iodine

A raised concentration of serum cardiac troponin I (cTnI) is a sensitive marker of cardiac myocyte injury in the cat and assays developed for its measurement in human patients have been validated in the cat. Raised levels have been associated with a number of cardiac insults including hypertrophic cardiomyopathy and trauma. Hyperthyroidism is a common disease of older cats and excess thyroid hormone is known to produce significant cardiovascular effects in this species. This study evaluated the effect of treatment for hyperthyroidism with radioactive iodine on cTnI concentration, assessed the association between thyroxin levels and glomerular filtration rate (GFR) and cTnI concentration in cats treated for hyperthyroidism and described changes in echocardiographic parameters following treatment. Prior to the treatment serum cTnI was measured and echocardiography performed, thyroxin, cTnI, and echocardiography were then repeated at various time points following radioisotope therapy. The results show that higher thyroxin levels were significantly (P=0.002) associated with a higher likelihood of the cat presenting with detectable levels of cTnI. No significant association was found between GFR and presence of detectable levels of cTnI. Furthermore the results indicate that the effects of hyperthyroidism on echocardiographic parameters appear considerably less in this study than in previous studies and that the main outcome of treatment on these parameters is a significant reduction in fractional shortening (P=0.006). These results suggest that chronic exposure to excess thyroid hormone may induce myocyte damage of sufficient severity to raise serum cTnI concentration in a proportion of cats that resolves following establishment of a euthyroid state.     

Evaluation of coagulation markers in the plasma of healthy cats and cats with asymptomatic hypertrophic cardiomyopathy

BACKGROUND: Thrombosis and arterial thromboembolism are frequent complications of feline cardiomyopathy, especially when associated with left atrial enlargement. Markers of activated coagulation may be used to evaluate the coagulation status of cats with hypertrophic cardiomyopathy (HCM) in relation to left atrial size. OBJECTIVES: The objective of this study was to compare plasma concentrations of thrombin-antithrombin complex (TAT), D-dimer, and fibrin degradation products (FDP) between clinically healthy cats and cats with HCM. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin activity were also compared and the association between left atrial (LA) size and coagulation results in cats with HCM was evaluated. METHODS: Blood samples from 19 clinically healthy cats and 20 cats with HCM were obtained. All cats with HCM were asymptomatic and had no signs of heart failure. LA diameter and LA to proximal aortic (Ao) diameter ratio (LA:Ao) were determined by echocardiography. RESULTS: Reference intervals for D-dimer and TAT concentrations in plasma of healthy cats were established as 0.09-0.32 microg/mL and 2.0-20.0 microg/L, respectively. TAT, D-dimer, and FDP concentrations were increased in 5, 3, and 2 cats with HCM, respectively. TAT and D-dimer concentrations, and PT and aPTT were not significantly different between groups. Antithrombin activity was significantly decreased in cats with HCM (P=.03) despite marked range overlap. LA and LA:Ao were not correlated with coagulation results. CONCLUSIONS: Laboratory evidence of hypercoagulability was found in 45% of cats with HCM. Left atrial size was not associated with laboratory evidence of hypercoagulability. Association between coagulation markers and risk of thrombosis has yet to be evaluated in cats with HCM.     

Quantitative renal scintigraphic determination of the glomerular filtration rate in cats with normal and abnormal kidney function, using 99mTc-diethylenetriaminepentaacetic acid.

The nuclear imaging technique known as quantitative renal scintigraphy was validated as a means to assess the kidney function of cats. Renal function tests were performed in 6 healthy cats and 3 cats with clinical manifestations of kidney failure. In addition, the nephrotoxic drugs, gentamicin sulfate, or amphotericin B were used in an attempt to induce renal failure in 4 cats. Using linear regression analysis, equations were derived to estimate the glomerular filtration rate (GFR) on the basis of the renal percent uptake of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). One-way ANOVA and Student's t test were used to evaluate treatment effects on clearances of inulin and creatinine, percent uptake of 99mTc-DTPA, and serum creatinine concentrations. The results show that the percent uptake of 99mTc-DTPA by the kidneys correlated well with the GFR obtained through the clearance of inulin. Thus, it was concluded that quantitative renal scintigraphy, using 99mTc-DTPA as a marker of kidney function, is an adequate technique to estimate the kidney function of healthy cats and cats with functional renal impairment. The best estimate of the GFR of cats, using the percentage dose of 99mTc-DTPA, was obtained on the 1- to 3-minute postinjection interval of the marker, using data that was background-subtracted, but not corrected for tissue absorption of gamma rays or binding of 99mTc-DTPA to plasma proteins. There was no significant difference in the mean inulin clearance, creatinine clearance, or percent uptake of 99mTc-DTPA between the 3 treatment groups of this study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of specimen collection and storage on blood glucose and lactate concentrations in healthy,hyperthyroid and diabetic cats

Abstract: The objective of this study was to compare and investigate differences in glucose and lactate concentrations in sodium fluoride/potassium oxalate (NaF/Ox) plasma and serum in healthy cats and cats with metabolic disease. Glucose and lactate concentrations were determined in routinely processed serum and NaF/Ox plasma obtained from healthy (n = 30), hyperthyroid (n = 27) and diabetic (n = 30) cats, and in samples from 6 healthy cats stored at 25°C or 4°C for 0,1, 2, 4, or 8 hours. The packed cell volume (PCV) of blood collected in NaF/Ox was compared with that of blood collected in EDTA. Mean glucose concentration was significantly (P < .05) lower in NaF/Ox plasma than in serum in all groups of cats, by 0.7–2.5 mmol/L (11–45 mg/dL); the difference was greater in cats with hyperglycemia. Mean lactate concentration was significantly higher in serum than in NaF/Ox plasma in all groups of cats, by 0.4–1.2 mmol/L (3.6–10.8 mg/dL); the difference was greater in hyperthyroid and diabetic cats. In vitro, only serum stored on the clot for ≥ 1hour at 25°C had significantly lower glucose and higher lactate concentrations. The PCV of NaF/Ox-anticoagulated blood was lower than that of EDTA-anticoagulated blood, by 7.0%± 1.4% (P<.01). In conclusion, collection of feline blood in NaF/Ox was necessary to prevent in vitro increases in lactate concentration; however, NaF/Ox artifactually decreased plasma glucose concentration because of RBC shrinkage. The PCV should not be determined on blood collected in NaF/Ox.