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.     

Results of thyroidectomy in 101 cats with hyperthyroidism

OBJECTIVE: To describe outcome after thyroidectomy in hyperthyroid cats, with emphasis on peri- and postsurgical complications and recurrence. STUDY DESIGN: Retrospective study. ANIMALS: One hundred and one hyperthyroid cats. METHODS: Diagnostic work-up included preoperative measurement of plasma calcium, sodium, potassium, urea, and creatinine concentrations, and thyroid scintigraphy. A modified intracapsular dissection technique was performed. Postoperatively, parathyroid gland function was evaluated by measuring plasma calcium concentration several times daily. Outcome was obtained by standard telephone questionnaire. RESULTS: Thyroid scintigraphy revealed ectopic hyperplastic thyroid tissue (EHTT) in 9 cats. Preoperatively, 29 of 91 cats had hypokalemia. Two cats died within 3 days after surgery and 5 of 86 cats developed postoperative transient hypocalcemia. On histologic examination, thyroid carcinoma was identified in 3 of 88 cats. Hyperthyroidism recurred in 5 cats between 3 and 59 months; 4 of these cats had EHTT preoperatively. The difference in recurrence rate between hyperthyroid cats with and without EHTT was significant (P<.001). CONCLUSION: Complications were uncommon after thyroidectomy performed by an experienced surgeon when combined with an anesthetic regimen associated with minimal adverse cardiovascular effects. Hyperthyroid cats with EHTT had a significantly higher chance of recurrence. CLINICAL RELEVANCE: Thyroidectomy is associated with a low incidence of surgical complications and is an effective treatment for hyperthyroid cats when radioactive iodine therapy is not available. Preoperative thyroid scintigraphy is advised. Surgery is not recommended when EHTT is present, because of a higher chance of developing recurrent disease.     

THYROID SCINTIGRAPHY FINDINGS IN 2096 CATS WITH HYPERTHYROIDISM

Thyroid scintigraphy is currently the reference standard for diagnosing and staging cats with hyperthyroidism, but few studies describing the scintigraphic characteristics in a large number of cats have been reported. The objective of this study was to better characterize thyroid scintigraphy findings by evaluating 2096 consecutive cats with hyperthyroidism that were referred over a 3.5‐year period. Of these cats, 2068 (98.7%) had a high thyroid‐to‐salivary ratio (>1.5), whereas 2014 (96.1%) were found to have a high thyroid‐to‐background ratio (>6.1). When the patterns of the cats’ thyroid disease were recorded, 665 (31.7%) had unilateral disease, 1060 (50.6%) had bilateral‐asymmetric disease (two thyroid lobes unequal in size), 257 (12.3%) had bilateral‐symmetric disease (both lobes similar in size), and 81 (3.9%) had multifocal disease (≥3 areas of increased radionuclide uptake). The number of areas of ^99mTcO^?₄ uptake in the 2096 cats ranged from 1 to 6 (median, 2), located in the cervical area in 2057 (98.1%), thoracic inlet in 282 (13.5%), and in the thoracic cavity in 115 (5.5%). Ectopic thyroid tissue (e.g. lingual or mediastinal) was diagnosed in 81 (3.9%) cats, whereas thyroid carcinoma was suspected in 35 (1.7%) of the cats. The results of this study support conclusions that most hyperthyroid cats have unilateral or bilateral thyroid nodules, but that multifocal disease will develop in a few cats that have ectopic thyroid disease or thyroid carcinoma. Both ectopic thyroid disease and thyroid carcinoma are relatively uncommon in hyperthyroid cats, with a respective prevalence of ～4% and ～2% in this study.     

Relationship between semi-quantitative thyroid palpation and total thyroxine concentration in cats with and without hyperthyroidism

In 155 cats, both with and without clinical signs of hyperthyroidism, total thyroxine (TT4) concentrations were compared to a sensitive, semi-quantitative thyroid palpation technique. On the basis of TT4 concentrations, 23 of the 155 cats were classified as hyperthyroid. The size of individual thyroid glands was scored between '0' (non-palpable) and a maximum of '6'. One or more enlarged thyroid glands (score >0) were palpated in 22 of the 23 hyperthyroid cats and in 78 of the 132 euthyroid cats. However, none of the 132 euthyroid cats had a thyroid lobe score of greater than '3' whereas 18 of the 23 hyperthyroid cats had a thyroid lobe score of '4' or greater, and in two of the five that had scores below '4' there was evidence of intrathoracic functional thyroid tissue on scintigraphy.     

Radioiodine treatment of hyperthyroidism

Radioactive iodine provides a simple, effective, and safe treatment for cats with hyperthyroidism and is regarded by most authorities to be the treatment of choice. It is a particularly useful treatment for cats with bilateral thyroid involvement (found in approximately 70% of cats), cats with ectopic (intrathoracic) thyroid tissue, and the rare patient with thyroid carcinoma. Treatment with radioiodine avoids the inconvenience of daily, oral administration of an antithyroid drug, as well as the side effects commonly associated with these drugs. Use of radioiodine also avoids the risks and perioperative complications associated with anesthesia and surgical thyroidectomy. Radioiodine treatment involves a single, nonstressful procedure that is without associated morbidity or mortality. A single treatment restores euthyroidism in most cats with hyperthyroidism. Whereas the therapy is simple and relatively stress-free for cats, it does require special licensing and hospitalization facilities, nuclear medicine equipment, and extensive compliance with local and state radiation safety laws.     

ULTRASONOGRAPHIC EXAMINATION OF THE THYROID GLAND OF HYPERTHYROID CATS: COMPARISON TO 99mTcO−4 SCINTIGRAPHY

High-resolution ultrasonography was evaluated as an alternative to ^99mTcO^-₄ scintigraphy for examining size and appearance of thyroid glands in hyperthyroid cats. Thyroid ultrasound examinations were performed on 6 normal cats and 14 cats with hyperthyroidism. Thyroid lobe volume was estimated from ultrasound images using the equation for a prolate ellipsoid, π/6 (length * height * width). Total thyroid volume was estimated by adding the volume estimations of the left and right lobes. Thyroid lobes of hyperthyroid cats were considered abnormal if estimated volume exceeded the 99% confidence interval for normal thyroid volume determined from the control group. Scintigraphic examinations performed on hyperthyroid cats were evaluated for unilateral versus bilateral disease and for the presence of ectopic activity. Mean thyroid lobe volume and total thyroid volume for normal cats was 85 and 169 mm³, respectively. Mean thyroid lobe volume and total thyroid volume for hyperthyroid cats was 578 and 889 mm³. There was a significant difference in mean estimated total thyroid volume of normal and hyperthyroid cats. Thyroid lobes with greater than normal TcO^-₄ uptake on scintigraphy were larger and had variable homogeneity, echogenicity, and margination on ultrasound examination. There also was an 85.7% agreement of scintigraphy and ultrasonography in differentiating normal from abnormal thyroid lobes. A fair correlation between estimated total thyroid volume of hyperthyroid cats and most recent pretherapy serum thyroxine values were also found. This preliminary study indicates that thyroid ultrasound examination may provide information that is useful for diagnosis and treatment of feline hyperthyroidism. Although ultrasound provides accurate evaluation of the thyroid glands, it cannot replace ^99mTcO^-₄ scintigraphy for screening of metastatic lesions and ectopic glands.     

Feline Thyroidectomy A Comparison of Postoperative Hypocalcemia Associated with Three Different Surgical Techniques

Three bilateral thyroidectomy techniques used in 41 hyperthyroid cats over a 7 year period were compared for rates of postoperative hypocalcemia. Extracapsular dissection of the thyroid glands resulted in an 82% rate of postoperative hypocalcemia. An intracapsular dissection technique produced a 36% rate of postoperative hypocalcemia. The incidence of postoperative hypocalcemia was reduced to 11% when bilateral thyroidectomies were done asynchronously (staged), 3 to 4 weeks apart. Immediate postoperative treatment with dihydrotachysterol did not reduce the incidence of postoperative hypocalcemia. Because the incidence of hypocalcemia did not differ significantly between intracapsular and staged intracapsular dissection, the authors concluded that staged bilateral thyroidectomy in hyperthyroid cats had limited benefit over simultaneous bilateral thyroidectomy.     

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.     

Radiographic and Scintigraphic Evidence of Focal Pulmonary Neoplasia in Three Cats With Hyperthyroidism: Diagnostic and Therapeutic Considerations

Three cats were diagnosed as hyperthyroid based on clinical signs, historical findings, laboratory abnormalities, and basal serum thyroxine (T₄) concentrations, and/or nuclear thyroid scans. Additionally, a presumptive diagnosis of thyroid carcinoma with pulmonary metastasis was made in each cat based on radiographic or scintigraphic evaluation. All three cats had solitary pulmonary nodules 1.5 to 2 cm in diameter on survey thoracic radiographs; one cat also had chylous pleural effusion and pulmonary lobar consolidation. Focal pulmonary accumulation of sodium pertechnetate (^99mTcO₄ -) and/or radioiodine (¹³¹I) corresponding to radiographic lesions were seen in all cats. Two cats were treated with single ablative doses (1111 to 1480 MBq) of¹³¹I; the remaining cat was euthanatized.
One of the treated cats died 8 days later; the other cat was euthanatized 22 weeks following treatment. Histopathologic examination of tissue obtained at necropsy confirmed metastatic thyroid carcinoma in one cat and bronchogenic adenocarcinoma in two cats. Our findings indicate that increased radionuclide uptake in focal pulmonary lesions and cytologic evaluation of tissue obtained by fine-needle aspiration are not specific for thyroid tissue. (Journal of Veterinary Internal Medicine 1993; 7:303–308. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

THYROID TO SALIVARY RATIOS DETERMINED BY TECHNETIUM-99M PERTECHNETATE IMAGING IN THIRTY-TWO EUTHYROID CATS

Thyroid to salivary (TS) ratio is the most commonly used scintigraphic parameter for differentiating euthyroid and hyperthyroid cats. Studies to determine the normal TS ratio have been performed in small cat populations. In this study, the TS ratio was determined in 32 cats between 8 and 13 years of age. The study population was documented to be euthyroid based on normal initial and 6-week follow-up serum thyroid concentrations and normal T3 suppression tests. All images were obtained with a low-energy all-purpose collimator between 20 and 40 min after the injection of approximately 111 MBq (3.0 mCi) pertechnetate. Manual regions of interest (ROI) were made of the thyroid and salivary glands of the ventral image A 95% prediction interval based on the natural log of the TS ratio was computed to provide a normal range of 0.48-1.66. This range is similar to previous studies, but suggests a slightly higher upper limit than previously reported.     

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.     

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.     

Expression of inhibitory G proteins in adenomatous thyroid glands obtained from hyperthyroid cats

OBJECTIVE: To identify within guanosine triphosphate-binding proteins (G proteins) the subset of inhibitory G proteins (G) that have decreased expression in adenomatous thyroid glands obtained from hyperthyroid cats. SAMPLE POPULATION: Adenomatous thyroid glands obtained from 5 hyperthyroid cats and normal thyroid glands obtained from 3 age-matched euthyroid cats. PROCEDURE: Expression of G(i1), G(i2), and G(i3) in enriched membrane preparations from thyroid glands was quantified by use of immunoblotting with G(i) subtype-specific antibodies. RESULTS: Expression of G(i2) was significantly decreased in tissues of hyperthyroid glands, compared with expression in normal thyroid tissue. Expression of G(i1) and G(i3) was not significantly different between normal thyroid tissues and tissues from hyperthyroid glands. CONCLUSIONS AND CLINICAL RELEVANCE: A decrease in G(i2) expression decreases inhibition of adenylyl cyclase and allows a relative increase in stimulatory G protein expression. This results in increased amounts of cAMP and subsequent unregulated mitogenesis and hormone production in hyperthyroid cells. Decreased G(i2) expression may explain excessive growth and function of the thyroid gland in cats with hyperthyroidism.     

QUALITATIVE AND QUANTITATIVE THYROID IMAGING IN FELINE HYPERTHYROIDISM USING TECHNETIUM-99M AS PERTECHNETATE

Thyroid imaging using technetium-99m as pertechnetate (^99mTcO₄) was carried out in five healthy, euthyroid and 37 hyperthyroid cats using both pinhole and parallel-hole collimators. Images of greater resolution, necessary to distinguish bilateral lobe involvement, were obtained using the pinhole collimator. Per cent thyriod ^99mTcO₄ - uptake was calculated in each cat and was significanly (P < 0.001) higher in hyperthyroid compared with euthyroid cats. In the hyperthyroid cats, per cent thyroid uptake was significantly correlated with serum total thyroxine (T4) and triiodothyronine (T3) Concentrations. Per cent thyroid ^99mTcO₄ - uptake is increased in feline hyperthyrodism and may be calculated using a pinhole collimator alone at the time of qalitative assessment of the extent of thyroid tissue involvement.     

Feline thyroid surgery.

Hyperthyroidism is the most commonly diagnosed endocrine disease in cats. Surgery is a widely available curative therapy for hyperthyroid cats. Because of the multiple metabolic changes associated with hyperthyroidism, surgical management can be challenging. Multiple methods of thyroidectomy and their associated levels of morbidity are reviewed.     

EFFECTS OF METHIMAZOLE ON THYROID GLAND UPTAKE OF 99MTC-PERTECHNETATE IN 19 HYPERTHYROID CATS

Nineteen cats with abnormally high serum T4 concentrations underwent thyroid scintigraphy using technetium-99m pertechnetate (99mTcO4) before and after 36 +/- 6 days of methimazole administration (approximately 2.5mg PO q 12 h). Thyroid-to-salivary gland ratios (T:S ratios) and percentage thyroidal uptake of injected radioactivity at 20 and 60min after injection of 99mTcO4 were compared before and after methimazole treatment. Serum thyroid stimulating hormone (TSH) concentration was measured before and after methimazole treatment. Quantitatively, there was a positive association between the thyroid uptake of 99mTcO4 and the serum T4 before treatment (r = 0.74-0.83). TSH suppression was present when cats were first evaluated for hyperthyroidism. Methimazole treatment did not relieve TSH suppression in 17 cats. Two cats with unilateral thyroid uptake developed bilateral, asymmetric thyroid uptake of 99mTcO4 after treatment and had the greatest increase in TSH concentration after treatment. Quantitatively, thyroid scintigraphy did not significantly change after methimazole treatment (P>0.1). Evaluation of serum TSH concentration may be helpful in identifying methimazole-induced changes in the scintigraphic features of hyperthyroidism in mildly hyperthyroid cats.     

PRE‐ AND POSTTREATMENT ULTRASONOGRAPHY OF THE THYROID GLAND IN HYPERTHYROID CATS

Ultrasonography is useful for assessing the morphology of the thyroid gland in hyperthyroid cats. Our aim was to describe the ultrasonographic changes of the thyroid gland in hyperthyroid cats after ¹³¹I therapy. Ultrasonography was performed in 15 hyperthyroid cats at initial presentation and 6 months after ¹³¹I using a multifrequency linear transducer set at 12 MHz. The following criteria were evaluated: length, width, height, volume, shape, homogeneity, and vascularity, using Power Doppler. Pretreatment, 10 cats had bilaterally abnormal thyroid lobes, four cats one abnormal lobe with the contralateral lobe being normal or reduced in size, and one cat with one normal lobe and one lobe not visible. Six months after ¹³¹I therapy, there was a reduction in median volume from 819 to 210 mm³, reduced rounding, reduced heterogeneity, and decreased vascularity. In conclusion, ultrasonography may be used to monitor thyroid changes in order to assess ¹³¹I treatment response. Further studies are necessary to determine whether ultrasonography could contribute to the detection of a relapsing course of hyperthyroidism.     

Optimal Testing for Thyroid Hormone Concentration after Treatment with Methimazole in Healthy and Hyperthyroid Cats

Background: Methimazole suppresses thyroid hormone synthesis and is commonly used to treat feline hyperthyroidism. The degree of variation in thyroid hormone concentrations 24 hours after administration of methimazole and optimal time for blood sampling to monitor therapeutic efficacy have not been determined.
Objective: To assess thyroid hormone concentration variation in serum of normal and hyperthyroid cats after administration of methimazole.
Animals: Four healthy cats and 889 retrospectively acquired feline thyroid hormone profiles.
Methods: Crossover and retrospective studies . In the crossover study, healthy cats were treated with increasing doses of oral methimazole until steady state of thyroid suppression was achieved. Thyroid hormones and thyroid stimulating hormone (TSH) were serially and randomly monitored after methimazole. Paired t -tests and a 3-factor analysis of variance were used to determine differences between thyroid hormone concentrations in treated and untreated cats in the crossover study. Thyroid profiles from methimazole-treated hyperthyroid cats were retrieved from the Diagnostic Center for Population and Animal Health database and reviewed. Linear regression analysis evaluated relationships of dosage (mg/kg), dosing interval (q24h versus q12h), and time after methimazole to all thyroid hormone concentrations.
Results: All serum concentrations of thyroid hormones were significantly suppressed and TSH was significantly increased for 24 hours after administration of oral methimazole in healthy cats ( P < .005). In hyperthyroid cats, there were no significant relationships between thyroid hormone concentrations and time postpill or dosing interval.
Conclusions: Timing of blood sampling after oral methimazole administration does not appear to be a significant factor when assessing response to methimazole treatment.     

COMPUTED TOMOGRAPHIC CHARACTERISTICS OF THE THYROID GLANDS IN EIGHT HYPERTHYROID CATS PRE‐ AND POSTMETHIMAZOLE TREATMENT COMPARED WITH SEVEN EUTHYROID CATS

Hyperthyroidism is the most common feline endocrinopathy; thyroid computed tomography (CT) may improve disease detection and methimazole dose selection. Objectives of this experimental pre‐post with historical case‐control study were to perform thyroid CT imaging in awake or mildly sedated hyperthyroid cats, compare thyroid gland CT appearance in euthyroid and hyperthyroid cats pre‐ and postmethimazole treatment, and determine whether thyroid size or attenuation correlate with methimazole dose needed for euthyroidism. Premethimazole treatment, eight hyperthyroid cats received CT scans from the head to heart, which were compared to CT of seven euthyroid cats. Total thyroxine levels were monitored every 3–4 weeks. Postmethimazole CT was performed 30 days after achieving euthyroid status. Computed tomography parameters recorded included thyroid length, width, height, attenuation, and heterogeneity. Median time between CT was 70 days (53–213 days). Mild sedation was needed in five hyperthyroid cats premethimazole, and none postmethimazole. Thyroid volume was significantly larger in hyperthyroid cats compared to euthyroid cats (785.0 mm³ vs. 154.9 mm³; P = 0.002) and remained unchanged by methimazole treatment (?4.5 mm3; P = 0.50). Thyroid attenuation and heterogeneity decreased with methimazole treatment (96.1 HU vs. 85.9 HU; P = 0.02. 12.4 HU vs. 8.1 HU; P = 0.009). Methimazole dose ranged from 2.5 to 10 mg daily with a positive correlation between pretreatment thyroid gland volume and dose needed to achieve euthyroidism (P = 0.03). Euthyroid and hyperthyroid cats are easily imaged awake or mildly sedated with CT. Methimazole in hyperthyroid cats significantly lowers thyroid attenuation and heterogeneity, but not size.