Altered expression of G proteins in thyroid gland adenomas obtained from hyperthyroid cats

OBJECTIVE: To determine whether expression of G proteins (G(i) and G(s)) is altered in thyroid gland adenomas obtained from hyperthyroid cats. SAMPLE POPULATION: Adenomatous thyroid glands obtained from 8 hyperthyroid cats and thyroid glands obtained from 4 age-matched euthyroid cats. PROCEDURE: Expression of G(i) and G(s) was quantified in enriched membrane preparations of thyroid gland tissue, using immunoblotting with G(i) and G(s) antibodies and toxin-catalyzed ADP-ribosylation. RESULTS: Expression of G(i) was significantly reduced in thyroid gland adenomas from hyperthyroid cats, compared with normal thyroid gland tissue from euthyroid cats. Expression of G(s) was similar between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: A decrease in expression of G in adenomatous thyroid glands of cats may reduce the negative inhibition of the cAMP cascade in thyroid cells, leading to autonomous growth and hypersecretion of thyroxine. Understanding the molecular mechanisms for hyperthyroidism in cats may lead to better treatment or, ultimately, prevention of the disease.     

Peripheral metabolism of thyroid hormones and iodide in healthy and hyperthyroid cats

The metabolic clearance rate, volume of distribution, and fractional clearance rate of thyroxine (T4), triiodothyronine (T3), and iodide were calculated for 6 healthy and 7 hyperthyroid cats, using single-compartmental and noncompartmental methods of analysis. The mean T4 volume of distribution of the hyperthyroid cats was 32.0% less than that of the healthy cats; it was the only variable that was significantly different (P less than 0.05) between these 2 groups of cats. The mean fractional clearance rate of T4 in the hyperthyroid cats was 53.2% greater than that in the healthy cats, but this difference was not significant. Hyperthyroid cats had no significant differences in T3 or iodide kinetic variables when compared with those in healthy cats. Single-compartmental analysis significantly overestimated T4 kinetic variables of healthy cats and T4, T3, and iodide kinetic variables of hyperthyroid cats when compared with the noncompartmental method of analysis.     

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.     

Radio-iodine treatment of hyperthyroid cats

Thirty-two elderly domestic shorthaired cats (mean age 12.9 years) were treated with radioiodine (131I). The dose of 131I administered ranged from 39 mBq to 134 mBq. Twenty-eight cats became euthyroid after treatment, one became hypothyroid and three remained hyperthyroxaemic. Two of the hyperthyroxaemic cats were successfully re-treated with 131I. Five cats died from concurrent diseases within one year of treatment. The administration of a dose of 131I selected by assessing the severity of the clinical signs, the size of the thyroid gland(s) and the serum level of thyroxine was an effective treatment for hyperthyroidism.     

Radio-iodine treatment of hyperthyroid cats

Thirty-two elderly domestic shdrthaired cats (mean age 12.9 years) were treated with radioiodine (¹³¹I). The dose of ¹³¹I administered ranged from 39 mBq to 134 mBq. Twenty-eight cats became euthyroid after treatment, one became hypothyroid and three remained hyperthyrox-aemic. Two of the hyperthyroxaemic cats were successfully re-treated with ¹³¹I. Five cats died from concurrent diseases within one year of treatment. The administration of a dose of ¹³¹I selected by assessing the severity of the clinical signs, the size of the thyroid gland(s) and the serum level of thyroxine was an effective treatment for hyperthyroidism.     

Within- and between-examiner agreement for two thyroid palpation techniques in healthy and hyperthyroid cats

Thyroid gland palpation is an important aid for diagnosing feline hyperthyroidism in an early stage to prevent development of deleterious complications. Our objectives were to assess within- and between-examiner agreement for two thyroid gland palpation techniques in cats and to correlate palpation results with ultrasonographic thyroid measurements. Nine client-owned hyperthyroid (12.6 +/- 2.4 years) and 10 healthy control cats (7.4 +/- 5.4 years) entered this prospective study. Both thyroid glands of all cats were palpated twice by three blindfolded clinicians with the classic palpation technique [technique 1 (T1)] and the technique described by Norsworthy GD, Adams VJ, McElhaney MR, Milios JA [(2002a) Relationship between semi-quantitative thyroid palpation and total thyroxine concentration in cats with and without hyperthyroidism. Journal of Feline Medicine and Surgery 4, 139-143] [technique 2 (T2)]. A semi-quantitative score from 1 to 6 was assigned to the gland size. After clipping of the ventral cervical region, another palpation session followed by ultrasonography of the thyroid glands was performed. Average weighted kappa-values within- and between-examiners were 0.864 and 0.644 for T1 and 0.732 and 0.532 for T2. T1 did lead to significantly smaller within- (P=0.007) and between-examiner (P=0.048) differences than T2. Significant correlation coefficients (P<0.001) between the palpation scores of both techniques and ultrasonographic thyroid lobe length (T1: 0.43; T2: 0.38) were observed. No significant difference before and after clipping was found (T1: P=0.503; T2: P=0.607). The first time that all cats were palpated by either technique, significant score differences between control and hyperthyroid cats were observed both for T1 (P=0.002) and T2 (P=0.003). Both feline thyroid gland palpation techniques have good within- and between-examiner agreements. Based on this study, the classic palpation technique is preferred.     

Thyroidal radioiodine uptake in hyperthyroid cats

Thyroidal radioiodine uptake was measured in 10 healthy domestic cats and in 20 hyperthyroid cats. Compared with those in the healthy cats, the uptake curves in the hyperthyroid cats were characterised by elevated uptake and rapid thyroidal iodine turnover. For diagnostic purpose uptake measurements at 4 hours after administration of the tracer were found to be preferable to measurements at 24 hours or later.     

Scintigraphic findings in 120 hyperthyroid cats

The aim of this study was to characterise the scintigraphic findings in a large population of hyperthyroid cats in order to determine the location of thyroid pathology in newly diagnosed hyperthyroid cats and those that had previously undergone thyroidectomy. A specific aim was to identify the proportion of cats with ectopic hyperfunctional thyroid tissue and characterise the scintigraphic and clinical features of this subset of cats. Nearly one in five hyperthyroid cats was identified to have multiple areas of hyperfunctional thyroid tissue and/or intrathoracic hyperfunctional thyroid tissue where surgical thyroidectomy would not be curative. In addition, this study demonstrated that scintigraphy cannot reliably distinguish between thyroid carcinoma and adenoma. Owners should always be warned about the possibility of ectopic thyroid tissue before thyroidectomy is performed. In this study, intrathoracic hyperfunctional thyroid tissue and multiple areas of increased radionuclide uptake (IRU) were a common feature of benign thyroid disease and responded well to treatment with low dose radioiodine.     

Thyroidal radioiodine uptake in hyperthyroid cats

Summary

Thyroidal radioiodine uptake was measured in 10 healthy domestic cats and in 20 hyperthyroid cats. Compared with those in the healthy cats, the uptake curves in the hyperthyroid cats were characterised by elevated uptake and rapid thyroidal iodine turnover. For diagnostic purposes uptake measurements at 4 houts after administration of the tracer were found to be preferable to measurements at 24 hours or later.     

Serum fructosamine concentrations in hyperthyroid cats.

Serum fructosamine concentrations were measured in 35 healthy cats and in 30 hyperthyroid cats before and 30 days after curative radioiodine ((131)I) treatment. Hyperthyroid cats were divided into those with 30 day post-treatment total thyroxine (T4) concentrations within (EuT4) or below (HypoT4) the reference range. The median (semi-interquartile range, SIR) fructosamine concentration was significantly lower in hyperthyroid compared with healthy cats (295. 0 (18.5) micromol l(-1)) both before (254.0 (27.6) micromol l(-1)) and after (268.5 (28.0) micromol l(-1)) treatment (P < 0.001 in each case). (131)I therapy was associated with increases in serum fructosamine (mean increase 20.4 micromol l(-1), P = 0.039) and total protein (6.3 g l(-1), P < 0.002) in the HypoT4 group and in globulin concentration in both EuT4 (5.9 g l(-), P < 0.002) and HypoT4 (5.2 g l(-1), P = 0.023) groups. There were no direct relationships between the observed elevations in fructosamine concentration and those in total protein or globulin concentrations suggesting that the effect may be due to reduced rates of protein turnover. Reduced values may need to be considered when interpreting serum fructosamine concentrations for monitoring the degree of glycaemic control in diabetic cats with concurrent hyperthyroidism.     

Serial determination of thyroxine concentrations in hyperthyroid cats

Serum thyroxine (T4) concentrations of 10 hyperthyroid cats were measured at hourly intervals between 9 AM and 4 PM. In 5 cats, blood samples were obtained by jugular venipuncture; the remaining 5 cats had blood samples obtained from jugular catheters. Over the 7-hour period, a significant temporal (diurnal) variation was not identified in the serum T4 concentrations of the cats (P greater than 0.01). The lowest mean serum T4 concentration (9.1 micrograms/dl) was measured at 3 PM and was 14.2% less than the highest mean serum T4 concentration (10.6 micrograms/dl) measured at 9 AM. Though there were fluctuations in serum T4 concentrations during the 7-hour period, the differences were not systematic. The maximal variation in serum T4 concentrations over the 7-hour period averaged less than 21%. Despite the random variations during the 7-hour period, none of the measured serum T4 concentrations was in the normal range. Measurement of serum T4 concentration from randomly obtained blood samples was determined to be reliable for diagnosing feline hyperthyroidism.     

Use of helical computed tomography for measurement of thyroid glands in clinically normal cats

OBJECTIVE: To determine the dimensions and volume of thyroid tissue in clinically normal cats by use of computed tomography. ANIMALS: 8 cats. PROCEDURE: Helical computed tomography images (2-mm collimation) were acquired from the cranial aspect of the second cervical vertebra through the caudal aspect of the fourth cervical vertebra. Data were acquired before contrast medium administration (n = 7 cats) and immediately after contrast medium enhancement (1 cat). Length, width, and height measurements of each thyroid lobe were made by use of transverse, dorsal, and sagittal plane images. Thyroid lobe volume was estimated by use of 3 methods. RESULTS: All thyroid lobes were histologically normal. Mean dimensions for a thyroid lobe were 16.5 x 2.00 x 4.31 mm (length x width x height) using only data from transverse images. Mean thyroid lobar volume was 113.75 mm(3) using the sum of areas method. Mean total volume of thyroid tissue was 215.25 mm(3) using the sum of areas method. CONCLUSIONS AND CLINICAL RELEVANCE: Results may be useful for computed tomography evaluation of abnormal thyroid glands in cats, which warrants investigation.     

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.     

The prevalence of feline immunodeficiency virus infection in hyperthyroid cats

One hundred and thirty-four male and female hyperthyroid cats (mean age 11.9 years) were tested for the presence of feline immunodeficiency virus antibodies. Thirty-two (23.9%) were positive. The prevalence of feline immunodeficiency virus antibodies was greater in male cats (30.5%) than in female cats (17.2%). The prevalence of feline immunodeficiency virus infection in hyperthyroid cats is similar to the prevalence of feline immunodeficiency virus in the sick cat population and less than that of sick aged cats at the Massey University Clinic and Hospital. The findings of this survey do not support involvement of feline immunodeficiency virus in the pathogenesis of hyperthyroidism in the cat.     

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.