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.     

Thyroidectomy in the cat

Thyroidectomy in cats is most commonly indicated to treat hyperthyroidism because of adenomatous hyperplasia of the thyroid glands. Preoperative stabilization of the hyperthyroid cat with antithyroid drugs is preferred to minimize anesthetic and surgical complications. Multiple surgical techniques for thyroidectomy have been reported, and results of surgery and complications differ between techniques. The extracapsular technique offers the most complete removal of abnormal thyroid tissue, while still being associated with a low incidence of postoperative hypoparathyroidism. Important postoperative considerations are to carefully monitor serum calcium concentrations and treat hypocalcemia if necessary, and to monitor the cat for evidence of relapse of hyperthyroidism.     

Thyroid scintigraphy in hyperthyroidism

Thyroid scintigraphy is a nuclear medicine procedure that produces a visual display of functional thyroid tissue based on the selective uptake of various radionuclides by thyroid tissue. Thyroid scintigraphy provides valuable information regarding both thyroid anatomy and physiology and can play an integral role in the diagnosis and management of cats with hyperthyroidism. Thyroid scintigraphy allows the direct visualization of the functional adenomatous thyroid tissue responsible for the development of hyperthyroidism. For this reason, thyroid scintigraphy will allow the diagnosis of hyperthyroidism before laboratory tests are consistently abnormal. Thyroid scintigraphy can also exclude a diagnosis of hyperthyroidism in cats with thyroid hormone elevations of nonthyroidal origin. Thyroid scintigraphy provides an additional method for determining the relative severity of thyroid disease that is less affected by the presence of concurrent nonthyroidal illness than laboratory evaluations. When treating hyperthyroid cats with radioiodine, the lowest effective dose should be administered. In an effort to administer the lowest radioiodine dose possible, the volume of adenomatous thyroid tissue present in the individual hyperthyroid cat should be considered. Thyroid scintigraphy provides an excellent method for evaluating the size of hyperfunctional thyroid tissue that is not limited by the presence of ectopic or intrathoracic thyroid tissue. Thyroid scintigraphy also provides valuable information in the diagnosis and evaluation of hyperthyroid cats with thyroid carcinoma.     

Evaluation of Environmental, Nutritional, and Host Factors in Cats with Hyperthyroidism

The pathologic changes associated with hyperthyroidism (adenomatous hyperplasia, adenoma of the thyroid gland) have been well characterized in cats, but the pathogenesis of these changes remains unclear. In this research, we undertook a case-control study to search for potential risk factors for this disease. Owners of 379 hyperthyroid and 351 control cats were questioned about their cats' exposure to potential risk factors including breed, demographic factors, medical history, indoor environment, chemicals applied to the cat and environment, and diet. The association between these hypothesized risk factors and outcome of disease was evaluated by conditional logistic regression. Two genetically related cat breeds (ie, Siamese and Himalayan) were found to have diminished risk of developing hyperthyroidism. Cats that used litter had higher risk of developing hyperthyroidism than those that did not. Use of topical ectoparasite preparations was associated with increased risk of developing hyperthyroidism. Compared with cats that did not eat canned food, those that ate commercially prepared canned food had an approximate 2-fold increase in risk of disease. When these 4 variables (breed, use of cat litter, consumption of canned cat food, and use of topical ectoparasite preparations) from the univariate analysis were selected for further study as candidate risk factors and analyzed by multivariate conditional logistic regression, a persistent protective effect of breed (ie, Siamese or Himalayan) was found. In addition, results suggested a 2- to 3-fold increase in risk of developing hyperthyroidism among cats eating a diet composed mostly of canned cat food and a 3-fold increase in risk among those using cat litter. In contrast, the use of commercial flea products did not retain a strong association. The results of this study indicate that further research into dietary and other potentially important environmental factors (eg, cat litter) is warranted.     

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.     

Palpable thyroid and parathyroid nodules in asymptomatic cats

Client-owned cats underwent surgery to remove palpable cervical masses in cats with normal total T4 values and no clinical signs of hyperthyroidism, renal disease, or hyperparathyroidism. Non-functional thyroid and parathyroid adenomas were found and identified by histopathological examination. The significance of these findings is discussed in relation to palpating a goiterous mass in an asymptomatic cat.     

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.     

Calcium homeostasis in thyroid disease in dogs and cats.

Hyperthyroidism is the most common endocrine disorder of cats, and hypothyroidism is the most common endocrine disorder of dogs. Little is known regarding the effects of hyperthyroidism, hypothyroidism, or treatment of these disorders on calcium metabolism in the dog or cat, however, especially any potential effects on bone. With better diagnostic tools, better treatments, and increased longevity of pets, the clinical impact of thyroid disorders on calcium metabolism and bone may be uncovered.     

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.     

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.     

CALCULATION AND USAGE OF THE THYROID TO BACKGROUND RATIO ON THE PERTECHNETATE THYROID SCAN

Feline hyperthyroidism is a common endocrine disorder. A single dose of 148 MBq (4 mCi) ¹³¹I is 95–98% effective for the treatment of hyperthyroidism in cats; however, the cause for treatment failures has not been determined. In a series of 113 hyperthyroid cats having pertechnetate thyroid scintigraphy before treatment using a standard 148 MBq (4 mCi) ¹³¹I dose, the thyroid to salivary gland (T:S) ratio and the thyroid to background (T:B) ratio were calculated. Results in 107 (95%) cats successfully treated were compared with results in six (5%) cats that remained hyperthyroid after treatment. T:B ratio was significantly higher for cats that had treatment failure (median 13.0, range 3.6–73.0) than for cats successfully treated (median 4.4, range 1.2–69.0) (P=0.02), whereas there was no significant difference in their T:S ratios (P=0.2). The T:B ratio is a new approach to evaluating the thyroid pertechnetate scan with the intent of identifying which hyperthyroid cats may fail treatment using a standard 148 MBq (4 mCi) ¹³¹I dose and which, therefore, require a higher dose.     

Recombinant human thyrotropin in veterinary medicine: current use and future perspectives

Recombinant human thyrotropin (rhTSH) was developed after bovine thyrotropin (bTSH) was no longer commercially available. It was approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) as an aid to diagnostic follow-up of differentiated thyroid carcinoma in humans and for thyroid remnant ablation with radioiodine. In addition, rhTSH is used in human medicine to evaluate thyroid reserve capacity and to enhance radioiodine uptake in patients with metastatic thyroid cancer and multinodular goiter. Likewise, rhTSH has been used in veterinary medicine over the last decade. The most important veterinary use of rhTSH is thyroidal functional reserve testing for the diagnosis of canine hypothyroidism. Recent pilot studies performed at Ghent University in Belgium have investigated the use of rhTSH to optimize radioiodine treatment of canine thyroid carcinoma and feline hyperthyroidism. Radioiodine treatment optimization may allow a decreased therapeutic dosage of radioiodine and thus may improve radioprotection. This review outlines the current uses of rhTSH in human and veterinary medicine, emphasizing research performed in dogs and cats, as well as potential future applications.     

ACCURACY OF INCREASED THYROID ACTIVITY DURING PERTECHNETATE SCINTIGRAPHY BY SUBCUTANEOUS INJECTION FOR DIAGNOSING HYPERTHYROIDISM IN CATS

Our purpose was to determine the accuracy of increased thyroid activity for diagnosing hyperthyroidism in cats suspected of having that disease during pertechnetate scintigraphy using subcutaneous rather than intravenous radioisotope administration. Increased thyroid activity was determined by two methods: the thyroid:salivary ratio (T:S) and visual inspection. These assessments were made on the ventral scintigram of the head and neck. Scintigraphy was performed by injecting sodium pertechnetate (111 MBq, SQ) in the right-dorsal-lumbar region; static-acquisition images were obtained 20 min after injection. We used 49 cats; 34 (69%) had hyperthyroidism based on serum-chemistry analysis. Using a Wilcoxon's rank-sum test, a significant difference (P < 0.0001) was detected in the T:S between cats with and without hyperthyroidism. Using a decision criterion of 2.0 for the T:S, the test accurately predicted hyperthyroidism in 32/34 cats (sensitivity, 94%; 95% confidence interval (CI), 85-100%) and correctly predicted that hyperthyroidism was absent in 15/15 cats (specificity, 100%; CI, 97-100%). Using visual inspection, the test accurately predicted hyperthyroidism in 34/34 cats (sensitivity, 100%; CI, 99-100%) and correctly predicted that hyperthyroidism was absent in 12/15 cats (specificity, 80%; CI, 56-100%). The positive and negative predictive values were high for a wide range of prevalence of hyperthyroidism. And, the test had excellent agreement within and between examiners. Therefore, detecting increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection is an accurate and reproducible test for feline hyperthyroidism.     

COMPARISON BETWEEN COMPUTED TOMOGRAPHY AND 99m TC‐ PERTECHNETATE SCINTIGRAPHY CHARACTERISTICS OF THE THYROID GLAND IN CATS WITH HYPERTHYROIDISM

Scintigraphy is currently the reference standard for diagnosing feline hyperthyroidism; however, computed tomography (CT) is more widely available in veterinary practice. The purposes of this prospective study were to describe the CT appearance of thyroid glands in cats with hyperthyroidism and compare CT findings with findings from ^99mTc–pertechnetate scintigraphy. Twenty‐five adult hyperthyroid cats were included. Plain CT images were acquired for each cat and the following characteristics recorded for each thyroid lobe: visibility, delineation, position, attenuation, shape, and subjective size. Scintigraphic images were also acquired and the following characteristics recorded: radiopharmaceutical uptake, delineation, ectopic foci, shape, and subjective size. In CT images, thyroid lobes were most commonly found between the second and fourth cervical vertebrae, dorsolateral to the trachea. Affected thyroid lobes (based on scintigraphy reference standard) were most commonly oval and moderately enlarged in CT images. A heterogeneous attenuation pattern (isoattenuating to adjacent soft tissues with hypo‐ and hyperattenuating foci) was most commonly found in affected thyroid lobes. A positive correlation (P < 0.01) was identified between CT and scintigraphy for left‐to‐right thyroid lobe size relationship and subjective size of the larger thyroid lobe. The CT estimated mass was significantly higher (median = 148.8; range = [0;357.6]) for the more active thyroid lobe compared to the less active thyroid lobe (median = 84.6; range = [0;312.3]); (W = 154; P < 0.01). Findings indicated that CT may not reliably differentiate unilateral vs. bilateral hyperthyroidism in cats; however, CT may be a reliable alternative test for correctly identifying the more active thyroid lobe.     

Functional cystic thyroid adenoma in a cat

A 9-year-old cat with hyperthyroidism was referred for radioactive iodine treatment. The cat also had a ventral cervical mass that the owners reported had been present for several years and had increased in size during the past few weeks. On physical examination, the mass was found to have caused lateral displacement of the trachea, esophagus, jugular vein, and common carotid artery. The mass was aspirated and was determined to be cystic in nature. Concentrations of thyroid hormones in the cystic fluid were similar to serum concentrations, and nuclear scintigraphy revealed thyroactive tissue lining the cyst wall. Magnetic resonance imaging suggested that the cyst originated from the right lobe of the thyroid gland. The cat was treated with sodium iodide I 131 but died 4 days later, presumably as a result of aspiration of gastric or esophageal contents. A necropsy was not performed, but histologic examination of a biopsy specimen of the mass indicated that it was a cystic thyroid adenoma.     

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.     

Feline Hyperthyroidism: A Case Report and Review of the Literature

A sixteen year old cat was examined because of polyphagia and weight loss. On the basis of elevated thyroxine levels and the clinical presentation a diagnosis of hyperthyroidism was made. The cat was treated presurgically with propylthiouracil and propranolol. Surgical excision of the grossly affected thyroid lobe, and partial excision of the apparently normal contralateral lobe was carried out. The cat improved clinically after the surgery but elevated thyroxine levels persisted. This case and the literature review, which is presented also, stress the necessity to either demonstrate unilateral involvement via extensive presurgical work-up, or to do bilateral, or staged bilateral thyroidectomies in cases of feline hyperthyroidism.     

INVESTIGATION OF TWO METHODS FOR ASSESSING THYROID-LOBE ASYMMETRY DURING PERTECHNETATE SCINTIGRAPHY IN SUSPECTED HYPERTHYROID CATS

Our aim was to investigate thyroid:thyroid (T:T) ratio and visual inspection for assessing thyroid-lobe asymmetry in suspected hyperthyroid cats. Although thyroid-salivary asymmetry is a preferred test, inherent thyroid symmetry may assist image interpretation. Association was determined using a scatter plot and Spearman's rank correlation. Agreement was assessed using the kappa (K) statistic. Accuracy was assessed by sensitivity and specificity. Hyperthyroidism was diagnosed in 33/48 (69%) cats based on elevated serum total thyroxine level. Using two Wilcoxan rank-sum tests, a significant difference (P < 0.0001) was detected between cats with and without hyperthyroidism for both methods of assessing thyroid symmetry. For the 18 cats with T:T ratios < or = 1.5, there was poor correlation between the two methods (r(s) = 0.39). Using a cut-point of 1.5 for the T:T ratio, the test accurately predicted hyperthyroidism in 28/33 cats (sensitivity, 85%; 95% confidence interval (CI), 71-99%) and correctly predicted that hyperthyroidism was absent in 14/15 cats (specificity, 93%; CI, 77-100%). For visual inspection, agreement for diagnosing hyperthyroidism was excellent between methods (kappa = 0.82), within the same examiner (weighted kappa = 0.85) and between examiners (weighted kappa = 0.89). Considering cats with only definitely asymmetric thyroid lobes as positive, visual inspection accurately predicted hyperthyroidism in 28/33 cats (sensitivity, 85%; CI, 71-99%) and correctly predicted that hyperthyroidism was absent in 11/15 cats (specificity, 73%; CI, 48-99%). Thyroid-lobe asymmetry occurs more frequently in hyperthyroid than in euthyroid cats but caution should be exercised because some euthyroid cats have asymmetric thyroid glands.