Thyroid Scintigraphy in Veterinary Medicine Gregory B. Daniel, DVM, MS, DACVR, and Dana A. Neelis, DVM, MS, DACVR Thyroid scintigraphy is performed in cats and dogs and has been used to a limited degree in other species such as the horse. Thyroid scintigraphy is most commonly used to aid in the diagnosis and treatment management of feline hyperthyroidism but is also used in the evaluation of canine hypothyroidism and canine thyroid carcinoma. This article reviews the normal scintigraphic appearance of the thyroid in the cat, the dog, and the horse and the principles of interpretation of abnormal scan results in the cat and the dog. Radioiodine is the treatment of choice for feline hyperthyroidism, and the principles of its use in the cat are reviewed. Semin Nucl Med 44:24-34 C 2014 Elsevier Inc. All rights reserved.
hyroid scintigraphy was one of the ﬁrst nuclear medicine procedures to be performed in veterinary medicine and still remains one of the most commonly requested scintigraphic studies.1,2 Access to nuclear imaging equipment and expertise needed to obtain a radioactive materials license limit the use of scintigraphy for the evaluation of thyroid disease in domestic species. Most veterinarians who offer nuclear medicine diagnostics or treatments for thyroid disease have had advanced training beyond their professional veterinary degree. It is possible for a general practice veterinarian to obtain a radioactive materials license, but the Nuclear Regulatory Commission (NRC) and agreement states require additional training. The most common nuclear medicine application for thyroid disease is iodine-131 treatment for feline hyperthyroidism. Most veterinarians consider radioiodine as the treatment of choice for hyperthyroidism in the cat.3 Thus, several commercial entities have been formed with the primary purpose of treating hyperthyroidism in cats with radioiodine. One organization, Radiocat, has performed radioiodine treatments in more than 50,000 cats since the business started in 1995. Thyroid disease is relatively common in the dog and the cat and is also reported in other veterinary species such as horses, ferrets, rabbits, rodents, and pet birds.4 Common disorders of the thyroid in domestic animal species include immunemediated thyroiditis (dog), idiopathic atrophy (dog), adenomatous hyperplasia (cat), and thyroid carcinoma (variety of
Department of Small Animal Clinical Sciences, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA. Address reprint requests to Gregory B. Daniel, DVM, MS, DACVR, Department of Small Animal Clinical Sciences, Virginia Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24060. E-mail: [email protected]
0001-2998/14/$-see front matter & 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semnuclmed.2013.08.007
species), or those caused by ingestion of goitrogenic substances or dietary imbalances (variety of species).4 Feline hyperthyroidism is the most common manifestation of thyroid disease in veterinary medicine.5 The second most common manifestation of thyroid disease is primary hypothyroidism in the dog.6-8 Some variation in the anatomy of the thyroid exists between veterinary species. In most domestic animals, the thyroid is composed of 2 separate lobes located on either side of the trachea just slightly distal and sometimes overlapping the larynx.9 An isthmus in the dog and the horse can connect these 2 separate lobes. During embryogenesis, there is a close anatomical relationship between the thyroid anlagen and those of other organs, including the hyoid bone, the neck muscles, and the primitive heart.10 As such, ectopic thyroidal tissue may be found from the base of the tongue to the base of the heart (Fig. 1). Sublingual ectopic tissue can become hyperplastic or undergo neoplastic transformation. Normal ectopic thyroid tissue may also be seen scintigraphically following thyroid removal (via tumor replacement or surgical excision). A large percentage of dogs have remnants of thyroidal tissue at the base of the aorta that can be seen on anatomical dissection, and this tissue can potentially become hyperactive or undergo neoplastic transformation.11 The size of the canine thyroid varies with the breed of dog. On average, the thyroid of the dog is 6 1.5 0.5 cm3 with a tendency to be larger in immature and brachiocephalic breeds.9 In the cat, thyroid size is more standardized owing to less variation in body size between feline breeds. The canine thyroid receives blood from both the cranial and caudal thyroid arteries but the cat thyroid receives blood supply only from the cranial thyroid artery.9 The venous drainage from the thyroid is through the cranial and caudal thyroid veins in both the dog and the cat. The efferent lymphatic drainage from the
Thyroid scintigraphy in veterinary medicine
Figure 1 Ventral (top images) and right lateral (bottom images) views of 3 different cats showing the various locations of ectopic thyroid tissue. All images were acquired 20 minutes following injection of Tc-99m-pertechnetate. The arrows point to the location of ectopic thyroidal tissue. The cat to the left has sublingual, the middle cat has cranial mediastinal, and the cat to the right has ectopic tissue at the base of the heart. All 3 cats have hyperthyroidism, with increased uptake by the cervical thyroidal tissue.
cranial one-third of the thyroid is into the medial retropharyngeal lymph nodes and the caudal aspects of the thyroid drain into the cervical lymph node chain. Therefore, metastasis from thyroid carcinoma can extend either cranially or caudally through the lymphatic system. The thyroid gland in the horse is located dorsal to the third through sixth tracheal rings and is composed of 2 lobes joined by a narrow ﬁbrous isthmus. Each lobe measures approximately 2.5 2.5 5 cm3.12 The thyroid gland is not normally visible externally but can be palpated.13
Thyroid Scintigraphy Thyroid scintigraphy is one of the most frequently performed veterinary nuclear medicine studies. In a survey of the members of the Society of Veterinary Nuclear Medicine, 84% of the respondents indicated they perform thyroid scintigraphy. There are a number of indications for thyroid scintigraphy in veterinary medicine as listed in the Table. In this article, we address many of the indications.
Normal Feline Thyroid Scintigraphy The appearance of the normal feline thyroid scan (using pertechnetate or radioiodine) is characterized by uniform distribution of radioactivity throughout both lobes of the thyroid gland (Fig. 2). The feline thyroid lobes appear as elongated ovals, symmetrical in size and position. The thyroid
lobe margins should be smooth and regular. Ectopic thyroid tissue is usually not seen in normal cats. The intensity of thyroid gland uptake is subjectively evaluated by comparing the thyroid gland uptake with the zygomatic salivary tissue.14 Quantitatively, this comparison can be done by region of interest (ROI) analysis using a count density ratio of the thyroid to the salivary glands.14-17 Normal cats have a thyroid-to-salivary ratio of 0.87:1 (range 0.6:11.03:1).14,16,18,19 Traditionally, thyroid imaging is performed 20 minutes after pertechnetate injection. Others have recommended imaging an hour after injection. However, the differences in uptake between 20 and 60 minutes are not signiﬁcant.19 Alternatively, the thyroid uptake ratios can be made comparing thyroid with background.20 The normal mean thyroid-to-background ratio is 2.76:1, with a range of 1.7-4.21 Quantifying thyroid function by measuring the percent of the injected dose of the radionuclide that Table Indications for Thyroid Scintigraphy (1) Evaluation of the functional status of the thyroid glands (2) Determination of unilateral or bilateral thyroid lobe involvement (3) Detection and localization of ectopic thyroid tissue (4) Differentiation between benign and malignant thyroid diseases (5) Determination of the origin of a cervical mass (6) Detection of functional metastasis (7) Evaluation of the efﬁcacy of therapy (8) Evaluation for residual tissue after thyroidectomy
G.B. Daniel and D.A. Neelis
Figure 2 Normal thyroid scans in the cat (left), the dog (central), and the horse (right). All images were acquired 20 minutes following injection of Tc-99m-pertechnetate. Ventral views are along the top and right lateral views on the bottom.
accumulates in the thyroid gland has been described but is rarely used clinically.16,19,22,23 These measurements are typically performed using a gamma camera as few places have thyroid detector probes. Normal thyroid percent dose uptake in cats 20 minutes after injection was reported by Mooney et al. to be 0.64% (mean) of the injected dose with a range of 0.25%-1.55%.23 Later, Nap et al.22 found that maximum uptake occurred between 45 and 60 minutes after injection, followed by a gradual decline, and that the range of thyroid uptake was from 0.8%-3.9% of the injected dose (median 2.2%). Neickarz and Daniel19 found that normal cats had percent dose uptakes of 0.21% ⫾ 0.06% (mean ⫾ standard deviation [SD]) and Lee et al.18 reported normal cats had percent dose uptakes of 0.38% ⫾ 0.09% (mean ⫾ SD). The differences in the reported values appear to be owing to variation in measurement technique.
Normal Canine Thyroid Scintigraphy The appearance of the normal thyroid scans in dogs is characterized by symmetrical uptake by paired thyroid lobes that are spherical to ovoid in shape (Fig. 2). The uptake is homogeneous and the margins are smooth and regular.24 The intensity of thyroid gland uptake can be compared with that of the parotid salivary gland or by determination of percent dose uptake.24-26 The normal thyroid-to-salivary ratio at 20 minutes is 1.12:1 ⫾ 0.13 (mean ⫾ SD).24 The reported range of percent dose uptake by euthyroid dogs is 0.39%-1.86%.24-26 Ectopic tissue is typically not seen on thyroid scintigraphic studies in normal dogs, but sublingual ectopic tissue is often seen following thyroidectomy.
Normal Equine Thyroid Scintigraphy The appearance of the normal thyroid glands in the horse is characterized by symmetrical uptake by paired thyroid lobes that are spherical to ovoid in shape (Fig. 2). The thyroid lobes are typically symmetrical in size and shape, although some asymmetry is found in horses without clinical evidence of thyroid disease.27 The uptake is generally homogeneous and the margins are smooth and regular, despite frequent identiﬁcation of thyroid nodules sonographically.27 The intensity of thyroid gland uptake can be compared with that of the salivary gland, but owing to variation in salivary uptake, it is recommended to use percent dose uptake.27
Common Thyroid Diseases in Veterinary Medicine Feline Hyperthyroidism Feline hyperthyroidism appears to be a relatively new disorder, ﬁrst being described in 1979.28 Since then, the prevalence of feline hyperthyroidism has steadily increased. Hyperthyroidism is one of the most frequently diagnosed disorders in small animal practice with the prevalence ranging from 4%-11% in areas such as the United States, Canada, the United Kingdom, Continental Europe, Australia, New Zealand, and Japan.5,29-31 Feline hyperthyroidism is now recognized as the most common endocrine disease of the cat. Feline hyperthyroidism is most commonly seen in middleaged to older cats, with 12-13 years being the average age at the time of onset.5,31 The etiology of hyperthyroidism in the cat is unknown; however, there are 2 major etiological theories: iodine deﬁciencies or excesses in cat food and exposure to thyroid-disrupting compounds.28 Chronic dietary iodine
Thyroid scintigraphy in veterinary medicine insufﬁciency leads to low circulating thyroid hormone concentrations. The autoregulatory mechanism of the pituitarythyroid axis leads to increased secretion of thyroid-stimulating hormone (TSH). Persistently high circulating TSH concentrations can result in thyroid hyperplasia to the point that the hyperplastic thyrocytes become autonomous to TSH, leading to adenomatous hyperplasia and then to thyroid adenoma formation.28 It has also been postulated that wide swings in daily iodine intake may contribute to development of thyroid disease.28,30 Feeding food from cans with ﬂip-top lids to cats is one known risk factor for developing hyperthyroidism. An epoxy resin, which contains the thyroid-disrupting compound bisphenol A, is found in the lining of cat food cans. The epoxy resin is intended to prevent corrosion thus improving shelf life of the product.28 Bisphenol A is a chemical of concern because it is an endocrine disruptor that can lead to thyroid dysfunction. One large study of control and cats with hyperthyroidism demonstrated an association between hyperthyroidism and cats fed food from “pop-top” cans.28 Moreover, certain ﬂavors of canned food such as ﬁsh, liver, or giblets seem to be risk factors for developing hyperthyroidism. In addition, exposure to certain chemicals such as those in ﬂame retardants, some insecticides, herbicides, or fertilizers have also been implicated as risk factors.3 The most common pathologic lesion resulting in hyperthyroidism is functional adenomatous hyperplasia. In most cases, the disease involves both thyroid lobes with unilateral involvement occurring in only 30% of cats with hyperthyroidism. In this disease, the normal thyroidal follicular architecture is replaced by well discernible foci of hyperplastic tissue that can form nodules ranging in size from less than 1-3 mm. The normal thyroidal tissue is often compressed between these areas of hyperplastic tissue. Because of the benign nature of adenomatous hyperplasia, the disease carries an excellent prognosis with effective therapy. The disease most closely resembles toxic nodular goiter in humans.5,31,32 The disease is dissimilar to Graves disease in that it does not appear to be an autoimmune disease as thyroid-stimulating immunoglobulins have not been demonstrated in cats with hyperthyroidism.30 In a small percentage of cats ( 2%), hyperthyroidism may be due to functional thyroid carcinoma. The thyrotoxicosis from the excessive circulating activity of thyroid hormones T4 and T3 results in multisystemic disease manifestation.3 Weight loss, in the face of polyphagia, is the most commonly recognized clinical sign in the cat. These cats are often hyperactive and exhibit nervousness, restlessness, and aggressive behavior. Owners report their cats exhibit anxiety and restlessness owing to aimless pacing and easily interrupted sleep patterns. Systemic manifestations of the thyroid toxicities include tachycardia, systolic murmurs, and a gallop rhythm that are due to phenotypic hypertrophic cardiomyopathy. This is a reversible form of the disease, which is different from idiopathic hypertrophic cardiomyopathy. These cats develop left ventricular hypertrophy, left atrial dilation, and increased fractional shortening. Systolic murmurs and gallop rhythms are frequently documented in cats with hyperthyroidism.33 The disease can result in cardiac failure in the absence of any underlying myocardial abnormality.
27 Palpable goiter can be seen in 80%-90% of cats with hyperthyroidism..34-36 A presumptive diagnosis of hyperthyroidism is typically based on history, clinical signs, and a physical examination ﬁnding of thyroid enlargement and on elevated T4 concentrations. However, clinical signs may be confused with other diseases, and diseased thyroid lobes may not be palpably enlarged or they may be located within the thoracic inlet making them inaccessible to physical examination. Measuring thyroid hormone (T4) concentrations can also help make a diagnosis of hyperthyroidism, as the test has a sensitivity of more than 90%; however, cats with early or mild manifestation of the disease may have T4 levels within the reference range. In addition, severe nonthyroidal illness can result in suppression of T4 concentrations such that cats with mild or early disease may have T4 values in the euthyroid range. Thyroid scintigraphy provides both functional and anatomical information that cannot be determined using any other single diagnostic procedure. The intensity of thyroid uptake correlates well with serum T4 concentrations.16 Thyroid scintigraphy also localizes the hyperfunctioning tissue to one or both thyroid lobes or ectopic sites of thyroid tissue.37 Thyroid scintigraphy has also been use to modulate radioiodine dose.20,38-40 The localization of hyperfunctioning thyroidal tissue via scintigraphy is critical for surgical planning.41 In cats with hyperthyroidism, hyperactive thyroid lobe(s) exhibit increased radionuclide uptake. This uptake may appear homogenous or may appear to arrive from multiple varying sized nodules. The hyperactive nodules are seen as focal areas of increased uptake. The appearance of hyperactive thyroid nodule(s) varies from enlargement of a portion of a thyroid lobe to hyperactive nodules at both ends of a thyroid lobe to a linear alignment of hyperactive nodules appearing as a “string of pearls” (Fig. 3). The surrounding normal thyroidal tissue is suppressed to varying degrees depending on the serum thyroxine concentration. Most often, hyperactive nodules are conﬁned to the area of the original thyroid lobes but they can extend outside the expected thyroid location in either a cranial or a caudal direction as ectopic tissues. A pinhole collimator can be used to resolve the distribution of the radionuclide within the lobes. The disease typically involves both thyroid lobes, but unilateral disease is seen in 30% of affected cats.42 True unilateral disease is characterized by increase uptake by one lobe and complete suppression of the contralateral thyroid (Fig. 4). In the cat, if one thyroid lobe exhibits markedly increased uptake and the opposite lobe exhibits normal or decreased uptake, both lobes are considered abnormal. Lack of complete suppression of a thyroid lobe despite marked increased uptake of the radioactivity of the paired thyroid gland is indicative of autonomous function. Asymmetric bilateral thyroid disease is often seen in cats with hyperthyroidism. Some cats with hyperthyroidism develop thin-walled ﬂuidﬁlled cysts within the thyroid. These cystic areas appear as photopenic voids on the thyroid scan. Often there are hyperactive nodules surrounding the photopenic area (Fig. 3). Ultrasound is useful to help conﬁrm the reason for the photopenic void in cases of cystic adenoma.
G.B. Daniel and D.A. Neelis
Figure 3 Thyroid scans in 6 different cats with hyperthyroidism. All images were acquired 20 minutes following injection of Tc-99m-pertechnetate. These images were acquired with a pinhole collimator and show some of the variation in uptake by multiple adenomas within the feline thyroid. Cystic adenomas can contain photopenic voids caused by the cyst (cats B and F).
Hyperfunctional malignant thyroid neoplasia is uncommon in cats, accounting for less than 2%-3% of feline hyperthyroidism cases. Thyroid carcinoma can have similar scintigraphic appearances to benign disease and scintigraphy cannot
reliably differentiate between them. However, there are scintigraphic patterns of activity that are associated with a higher probability of carcinoma. The thyroid tends to be larger with higher radionuclide uptake in cases of thyroid
Figure 4 Thyroid scans in 3 different cats with hyperthyroidism. All images were acquired 20 minutes following injection of Tc-99m-pertechnetate. The top images are ventral views, the middle images were obtained using a pinhole collimator, and the bottom images are right lateral views. The pinhole collimators show the uptake originating from multiple hyperactive nodules. The cat on the left has bilateral symmetrical disease involving both thyroid lobes. The cat in the middle also has bilateral involvement of the left and right thyroid lobes but the uptake is asymmetrical. The cat on the right has unilateral disease only involving the left thyroid lobe. Note the right lobe uptake is suppressed through the thyroid-pituitary axis. Unilateral disease only occurs in 30% of cats with hyperthyroidism.
Thyroid scintigraphy in veterinary medicine carcinoma. Carcinomas may have a heterogeneous pattern of uptake with irregular, spiculated margins. A multifocal pattern of uptake with foci of uptake outside the conﬁnes of the thyroid lobes indicates a higher probability of carcinoma. Accumulation of either pertechnetate (99mTcO4) or radioiodine (123I) within the mediastinum or lung or both may be seen in cats or dogs with functional metastases. Differential diagnosis for radionuclide uptake in the cranial mediastinum would also have to include hyperplastic ectopic thyroid tissue. Focal accumulation of radionuclide within the lung is usually associated with metastatic thyroid tumors. However, both thyroid and pulmonary tumors may demonstrate increased radionuclide uptake.43 It has been shown that a number of drugs and other compounds can interfere with iodide or 99mTcO4 uptake by the thyroid. Iodinated radiographic contrast media is known to reduce thyroid uptake. Cats may receive iodinated contrast for a variety of reasons, most common today being for CT studies. In a controlled study in normal cats, nonionic contrast media signiﬁcantly reduced thyroid uptake but not outside the normal reference ranges.18 The inﬂuence of ionic radiographic contrast is unknown in the dog or that cat but may have a greater effect on thyroid uptake. Antithyroid medications are commonly used as a medical treatment of hyperthyroidism in the cat.3,31,44 Methimazole is a commonly used antithyroid drug in cats, which acts by blocking iodine organiﬁcation and thyroid hormone production. The drug does not directly affect the NaI symporter that is responsible for trapping iodine by the follicular cell.45,46 Antithyroid medications have been shown to cause a signiﬁcant increase in the thyroid uptake of pertechnetate and radioiodine in normal thyroid tissue (Fig. 5).19,47 The increased trapping by normal thyroid tissue continues for 15 days after withdrawal of the medication.19 This is likely owing to upregulation of the NaI symporter in response to high TSH concentration secondary to low serum T4.19 Elevated TSH increases all activities of the thyroid follicular cells including iodide trapping, iodination and the coupling process, cellular hyperplasia, and increased secretion of stored T3 and T4. Enhanced thyroid uptake shortly after discontinuing methimazole has previously been hypothesized as a “short-term rebound effect.” This effect has been shown to increase radioiodide uptake shortly after discontinuing methimazole.48 This enhanced uptake of pertechnetate or radioiodine in normal tissue caused by methimazole is clinically signiﬁcant because the clinical signs of hyperthyroidism can be confused with other nonthyroidal diseases. If these cats are erroneously diagnosed with hyperthyroidism, treated with methimazole, and later undergo thyroid scintigraphy, they have an elevated thyroid uptake, which solidiﬁes the false impression of hyperthyroidism.
Canine Hypothyroidism Hypothyroidism is the most common canine endocrinopathy.25 Canine primary hypothyroidism is the most common form of the disease, although secondary, tertiary, and congenital forms of the disease are also seen. Primary hypothyroidism
Figure 5 Thyroid scans in a normal cat acquired 20 minutes following injection of Tc-99m-pertechnetate. The images on left were obtained before and the images on the right after 3 weeks of the antithyroid drug, methimazole. Note the increased uptake by both thyroid lobes following methimazole. Methimazole blocks T4 formation and lowers serum concentrations, which in turn results in increased TSH levels and an increase uptake by normal thyroidal tissue.
is often secondary to an autoimmune lymphocytic thyroiditis.8 These dogs develop autoantibodies to thyroglobulin that result in gradual destruction of the thyroid gland. Follicular atrophy is the end stage of thyroiditis. Idiopathic thyroid degeneration may be the result of lymphocytic thyroiditis or other primary pathologic conditions. This disease is characterized by loss of thyroid parenchyma with replacement by ﬁbrosis or adipose tissue. The onset of primary hypothyroidism is usually gradual, taking months to even years. It is most common in middleaged dogs with 7 years being the typical age at diagnosis. The disease is more common in purebred animals. Dogs with hypothyroidism are usually diagnosed by measurement of total or free T4 in combination with canine TSH concentrations.8 The use of thyroid scintigraphy is helpful to conﬁrm the diagnosis, which can be especially important in the presence of nonthyroidal illness.25 Scintigraphy can differentiate between congenital hypothyroidism caused by thyroid dysgenesis (thyroid glands are not visualized on the thyroid scan) and due to inherited iodination defects (thyroid scan shows large thyroid lobes with normal to increased radionuclide accumulation).25,26,49-51 Dogs with low serum thyroid hormone concentration caused by factors not directly related to the thyroid gland (euthyroid sick syndrome) have normal to slightly increased thyroid uptake even on initial studies. Thyroid scintigraphy is used to assess thyroid gland function in the dog.7,25,26 Although the intensity of uptake correlates
G.B. Daniel and D.A. Neelis
30 with metabolic function in the cat, this may not always be true in the dog.25 Dogs with Hypothyroidism have diminished thyroid uptake.52,53 However, increased uptake by the thyroid can occur with thyroid carcinoma in dogs that often have normal or subnormal T4 concentrations.7,54 It has been shown that calculating the percent dose uptake is superior to thyroidto-salivary ratios in the dog owing to variations in salivary gland uptake.26
Canine Thyroid Carcinoma Thyroid scintigraphy is useful to determine whether cervical masses in dogs are originating from thyroid tissue or from other nonthyroidal tissue. This is especially useful when cytology or histopathology results are equivocal. Differentials for a cervical mass in the dog include thyroid neoplasia, salivary neoplasia, lymphoma, carotid body tumors, metastatic extension of head and neck tumors, salivary mucocele, sialadenitis, foreign body, or granuloma.54 Thyroid carcinoma is the most common endocrine tumor in the dog.55 Most thyroid tumors are carcinomas and can arise from either follicular or parafollicular cells. Follicular thyroid carcinomas are more common and have been histologically classiﬁed as follicular, compact, and mixed.56 There is increased uptake of the radionuclide by
most of the follicular cell tumors, and therefore the thyroid scan can be used to help stage the diseases.42,57-59 When the cervical mass arises from the thyroid, the appearance of the thyroid gland would be abnormal.60 When the mass arises from tissues other than the thyroid, both thyroid lobes should exhibit a normal size and radionuclide uptake. Often the normal thyroid gland is displaced by the nonthyroidal mass. The scintigraphic appearance of canine thyroid carcinoma can vary regarding intensity and size. Approximately 80%90% of dogs with thyroid carcinoma have nonfunctional lesions in that they do not produce functional hormones and are clinically euthyroid or hypothyroid.54 Usually the thyroid tumor involves only one lobe and the uptake in the contralateral lobe is not completely suppressed. Three common uptake patterns can be seen as follows: (1) diffuse increase in uptake throughout the thyroid mass (follicular cell tumor or adenoma); (2) thyroid mass with decreased uptake of the radionuclide, effacing the normal thyroid tissue (stromal-origin tumor); and (3) irregular, multifocal areas of radionuclide accumulation with areas of both increased and decreased uptake (mixed cell tumor) (Fig. 6). The appearance of the thyroid gland can also be characterized by its margins. Some tumors have well-deﬁned borders and other masses have ill-deﬁned or spiculated borders. An interpretation scheme has
Figure 6 Thyroid scans in 4 different dogs with thyroid carcinoma show different patterns of uptake. All images were acquired 20 minutes following injection of Tc-99m-pertechnetate. The top images are ventral views and the bottom images are right lateral views. The images in the middle are zoomed images. Dog A has a thyroid carcinoma of the right thyroid lobe. The tumor has increase pertechnetate uptake but is not producing excess T4 and therefore the left lobe is not suppressed. Dog B has a thyroid carcinoma of the left lobe which is nonfunctional in that it does not have increased uptake nor is it suppressing the contralateral lobe uptake. Dogs C and D have inﬁltrative thyroid carcinoma. Dog C has unilateral disease involving only the left thyroid lobe. Dog D has bilateral disease involving both the left and right thyroid lobes. Dogs A and B are representative of type I pattern and dogs C and D representative of type II pattern (refer to text).
Thyroid scintigraphy in veterinary medicine been proposed in which the scintigraphic appearance is divided into 2 patterns. Pattern I is a thyroid mass with wellcircumscribed homogenous radionuclide uptake. Pattern II is a poorly circumscribed thyroid mass with heterogeneous radionuclide uptake (Fig. 6).60 The patterns did not predict the tumor type but were helpful in predicting the surgical resectability of the mass. Thyroid masses with poorly circumscribed margins are associated with capsular invasion by the tumor and likely represent invasive thyroid carcinoma. Thyroid masses with well-circumscribed margins tended to be more likely for complete surgical resection to be possible.60 This is an important prognostic factor in that invasive thyroid carcinoma carries a poor prognosis owing to both local invasion and a higher rate of metastasis.61 Scintigraphy is useful to help stage the disease as the tumors can spread through the lymphatics or the blood stream.56 Tumor spread in a cranial or caudal cervical direction indicates likely extension of the carcinoma along lymphatic structures or invasion along fascial planes. Lymphatic drainage from the cranial pole of the thyroid is to the submandibular lymph node and then to the medial retropharyngeal lymph node. Tumor extension to the medial retropharyngeal lymph node is seen as a mass dorsal to the trachea and lateral to midline and is easily differentiated from sublingual ectopic thyroid tissue which is seen ventral to the pharynx or larynx and located on midline. Mediastinal uptake of the radionuclide may represent tumor extension through lymphatic tissue, by ectopic thyroid tissue stimulated by TSH or by neoplastic transformation of ectopic tissue. Ectopic thyroidal tissue is common in the dog. Approximately 50% of adult dogs have ectopic thyroidal tissue embedded in the fat on the intrapericardial portion of the aorta or within the right ventricle (struma cordis).11,54 Uptake in the area of the heart base is seen in dogs and could represent stimulation of the remnant of thyroidal tissue secondary to elevated endogenous TSH or its neoplastic transformation (Fig. 7). Pulmonary metastatic lesions may be seen as focal areas of uptake within the pulmonary parenchyma (Fig. 7). Scintigraphy is inferior to radiographs or better yet CT for the evaluation of pulmonary metastasis. The detection of pulmonary metastasis with scintigraphy would be better once the primary tumor has been surgically removed. 123 I is superior to 99mTcO4 for detecting intrathoracic extension of the disease owing to the higher target to background ratios. Because 123I is both trapped and organiﬁed, radioiodine images are obtained at 24 hours, which allows additional time for the blood pool activity to clear. Small or low intensity uptake lesions that are difﬁcult to impossible to see on the pertechnetate scans are more easily detected with radioiodine. The dose of radioiodine is typically 250-500 μCi, which is one-tenth the dose of pertechnetate. As a result, there is a low photon ﬂux coming from a patient that requires longer acquisition times. It is difﬁcult to maintain an animal without motion for these long periods; therefore these images are of much lower count density. Often it is best to perform both the radioiodine and the pertechnetate scans on the same day. This can be accomplished by orally administering the radioiodine capsule the day before
Figure 7 Thyroid scans in 2 different dogs with thyroid carcinoma. All images were acquired 20 minutes following injection of Tc-99mpertechnetate. The top images are ventral views of the thorax and the bottom views are right lateral views of the thorax. Uptake in the stomach can be seen caudally in each image. The images on the left are from a dog with uptake from thyroidal tissue at the base of the aorta (arrow head). The images on the right are from a dog with multiple pulmonary metastases (arrow).
the scan. The radioiodine scans are acquired, and then the animal is injected with pertechnetate at 10 times the original dose of 123I. Twenty minutes following intravenous injection of pertechnetate, the scan is repeated. This allows a high-count density pertechnetate scan to be compared with the low-count density radioiodine scan. Thyroid hormone supplementation reduces TSH concentrations and reduces thyroid uptake for several weeks, which is an important consideration when performing thyroid scans on dogs following thyroidectomy for carcinoma. These dogs are frequently given thyroid supplementation to reduce TSH to prevent any growth-stimulating effects in residual thyroidal tissue.31
Treatment of Feline Hyperthyroidism with Radioiodine Radioiodine therapy is considered the treatment of choice for treating feline hyperthyroidism. Radioiodine is simple, effective, and safe without signiﬁcant morbidity or mortality. Alternative treatments include antithyroid drug therapy, surgical resection, or dietary management. Each treatment choice has advantages and disadvantages. Feline hyperthyroidism can be controlled by medical treatment. The treatment is widely available through local veterinarians. Owner compliance with the treatment regime can be affected by the difﬁculty in pilling the cats. There are transdermal delivery methods for the antithyroid medication, but
32 many owners do not want to medicate their cat on a daily basis for the rest of the cat's life. The antithyroid medications are also associated with side effects such as loss of appetite and vomiting. More serious reactions include thrombocytopenia, leukopenia, and hepatopathy. Surgery is an effective method for treating hyperthyroidism by removing the abnormal thyroidal tissue. It is best if the abnormal tissue is identiﬁed by scintigraphy before surgery. The abnormal thyroid lobes may appear grossly normal, and if not removed, the hyperthyroidism will not be cured. There is also the possibility of ectopic abnormal tissue being located within the thorax. As a result, hyperthyroidism may reoccur a few months to years following surgical treatment. As the disease is most often bilateral, both thyroid lobes commonly need to be removed. Removal of both lobes increases the risk of removal or damage to the adjacent parathyroid glands during thyroid surgery. This can result in hypocalcemia from hypoparathyroidism. This complication can be lifethreatening and results in additional hospitalization stay and cost. Hill's, a major pet food company, has recently released a thyroid health diet (y/d). This is a prescription diet formulated to reduce T4 levels in cats with hyperthyroidism. The diet is deﬁcient in iodine, which inhibits the ability of the thyroid gland to produce T4. Most cats with hyperthyroidism that are fed this diet exclusively will have T4 levels within the normal range in 4-12 weeks. This diet is controversial and many question the wisdom of feeding an iodine-deﬁcient diet to cats with hyperthyroidism, as this is one of the known risk factors in developing the disease. Moreover, many argue the long-term effects of feeding an iodine-deﬁcient diet, which is unknown. Radioiodine is an easy and effective treatment for feline hyperthyroidism. Radioiodine is administered as a subcutaneous injection without the need for general anesthesia or the risk of developing hypoparathyroidism. It is effective in that more than 85% of cats with hyperthyroidism have normal T4 levels in 2 weeks and 95% with T4 levels normal in 3 months of administration.62 Pretreatment considerations include the evaluation for renal disease. There are a signiﬁcant number of cats that become azotemic following radioiodine therapy.63,64 The hyperthyroidism creates a hyperdynamic state that maximizes the animal's glomerular ﬁltration rate by increasing renal blood ﬂow. This can mask underlying renal disease in the cat with hyperthyroidism and the renal disease may become apparent following successful treatment for hyperthyroidism. Therefore, it is recommend that the cat's renal function be assessed before radioiodine therapy. This can be done by performing a renal glomerular ﬁltration rate scan or maintaining the animal's euthyroid status by administration of antithyroid medication for 1 month and determining if the animal becomes azotemic. The 131I is intended to destroy or kill the hyperfunctioning tissues and spare the normal follicular thyroid cells, that is, resolve hyperthyroidism without creating hypothyroidism. The optimal method for determining the 131I dose required to achieve this goal remains somewhat controversial. The reported
G.B. Daniel and D.A. Neelis methods used to calculate the radioiodine doses are quite variable but can be divided into 3 different methodologies. The most complicated and least used method is to determine the 131I dose based on the desired radiation dose delivered to the thyroid. This method requires the use of tracer studies to estimate the percentage of iodine uptake and rate of disappearance (biological half-life) from the gland. The method also requires an estimation of the weight of the gland.38 Theoretically, this method should produce the best results but there are several potential errors such as estimation of thyroid gland weight and the ability to predict biological half-life of the therapeutic dose from the tracer dose. This can result in differences between the calculated dose and the actual radiation dose delivered to the thyroid tissue. The time and expertise needed to do these procedures and calculations also limit the use of this technique. The most common technique used is a ﬁxed empirical dose, typically 4 mCi. Cats with hyperthyroidism are given this relatively high dose of radioiodine, regardless of the severity of hyperthyroidism or size of thyroid. This method is effective in resolving the hyperthyroidism and alleviating the high T4 levels in most cats. Recently, it has been noted that, at least serologically, hypothyroidism developed in a signiﬁcant percentage of the cats. Although this method is the simplest, there is a concern that we are over treating a number of cats. The third method of dose determination is a hybrid between the ﬁrst 2. The dose of radioiodine administered to cats with hyperthyroidism is determined on the basis of a scoring system that factors in the severity of clinical signs, results of thyroid imaging, thyroid size and uptake, and the serum T4 concentration.65 Three different doses are selected based on this scoring system. A low dose (3 mCi) is used for cats with mild clinical signs, small thyroid tumors, and only slightly high serum T4 concentrations. A high dose (5-6 mCi) is reserved for cats with severe clinical signs, very large thyroid tumors, and markedly high serum T4 concentrations. A middle dose (4 mCi) is used for cats that lie between these extremes.62 Following treatment, the animals remain hospitalized in an isolation area until their external exposure rate is below the limits set by the facility's radiation safety regulations. This is typically 3-10 days. The major disadvantages of radioiodine therapy are the regulatory restrictions that are associated with the dose and the patient following injection. Radiation safety precautions for animals are stricter than those for human patients. The provisions set forth by the NRC for veterinary use of radioactive materials is found in Part 30 “Rules of General Application to Domestic Licensing of Byproduct Material” and Part 31 “General License for Use of Byproduct Material for Certain In Vitro Clinical and Laboratory Testing.” The provisions for human patients are found in Part 35 “Medical Use of Byproduct Materials.” Basically, radioactive veterinary patients are considered radioactive materials. As most states set their own regulations as agreement states, there is considerable variability on the regulation of veterinary nuclear medicine, but all must meet the minimal requirements of the NRC. The difference in regulations between human and veterinary patients is largely owing to the greater potential for environmental contamination by urination and defecation.
Thyroid scintigraphy in veterinary medicine Regulations differ depending on the agency licensing the facility; however, all facilities are required to conﬁne the animal for some time after the administration of a radionuclide. The release criteria allow the animal to leave isolation when the external radiation exposure level has reached a point deemed to be safe for the general public. At the authors' institution, the patient can be released when the radioactivity measured at 1 m from the patient does not exceed 0.5 mR/h. Most cats reach this level at 5 days following radioiodine therapy. The cats are discharged knowing they will still be excreting a small amount of radioiodine in their urine and feces. The remaining radioactivity will be gradually eliminated from the cat over the next 2-4 weeks. Owners must agree to obey safety precautions after their cat is discharged following 131I treatment. These instructions are written out and the owner signs the agreement. The exact precautions are dictated by the agency licensing the facility and are designed to protect human beings from excessive radiation exposure. Most of the precautions state that the cat must be kept strictly indoors for some time, typically 2 weeks. The members of the animal's house are to have minimal contact time with the cat during this period. The cat is not to sleep with them or sit on their lap. Contact with children younger than 18 years and pregnant woman during the ﬁrst 2 weeks in usually prohibited. The owners are to wear disposable gloves when handling the animal's waste.
Conclusion Thyroid diseases are very commonly encountered in veterinary medicine. Nuclear scintigraphy remains one of the most used methodologies for imaging the thyroid glands, as this form of imaging provides both functional information and localization of the abnormal thyroid tissue. Additionally, nuclear medicine, such as radioiodine therapy, is routinely used in veterinary medicine, most commonly for the treatment for feline hyperthyroidism.
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