Chapter 21: Radioiodine for Feline Hyperthyroidism

Web Chapter 21


Radioiodine for Feline Hyperthyroidism




Hyperthyroidism is the most common endocrine disorder in cats, most frequently associated with adenomatous hyperplasia (or adenoma) involving one or both thyroid lobes. Because the exact pathogenesis of hyperthyroidism in cats is not known, treatment of the condition is directed at controlling the excessive secretion of thyroid hormone from the adenomatous thyroid gland. Treatment options include administration of an antithyroid drug (e.g., methimazole), chronic feeding of an iodine-deficient diet (Hill’s y/d), surgical thyroidectomy, and administration of radioiodine (131I) to irradiate and destroy the hyperfunctional thyroid nodule(s). Although each of these treatment options has its advantages and disadvantages, radioiodine is considered by most authorities to be the treatment of choice for most the majority of hyperthyroid cats.


Radioactive iodine provides a simple, effective, and safe treatment for cats with hyperthyroidism. It is particularly useful for cats with bilateral thyroid involvement (found in approximately 70% of cats), cats with intrathoracic (e.g., ectopic) thyroid tissue, cats that fail to respond adequately to medical or nutritional management, and the relatively rare feline patient with thyroid carcinoma. Treatment with radioiodine avoids the inconvenience of daily oral administration and side effects associated with antithyroid drugs, the restrictions associated with the lifelong feeding of an iodine-deficient diet, and the risks and postoperative complications associated with anesthesia and surgical thyroidectomy.


Although 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. There are also different protocols that facilities may use to determine the cats’ radioiodine dosage, which greatly influences the prevalence of persistent hyperthyroidism (when the administered 131I dose is too low) and iatrogenic hypothyroidism (when the administered 131I dose is too high).


This chapter gives an overview of aspects of radioiodine treatment germane to the practicing veterinarian who is referring hyperthyroid cats for this treatment.



Mechanism of Action of Radioiodine Treatment


Thyroid hormones are the only iodinated organic compounds in the body. Ingested stable iodine (127I) is converted to iodide in the gastrointestinal tract and absorbed into the circulation. In the thyroid gland, iodide is concentrated or trapped by active transport mechanisms of the thyroid follicular cell, resulting in intracellular iodide concentrations that are 10 to 200 times that of serum. Once inside the thyroid cell, iodide is oxidized to iodine, which is incorporated into tyrosine residues of thyroglobulin (organification) to form the thyroid hormones thyroxine (T4) and 3,5,3′ triiodothyronine (T3).


The radioisotope used to treat hyperthyroidism is radioiodine (131I). The basic principle behind treatment of hyperthyroidism with 131I is that thyroid cells do not differentiate between stable and radioactive iodine; therefore 131I, as with stable iodine, is concentrated by the thyroid gland after administration. In cats with hyperthyroidism, radioiodine is concentrated primarily in the hyperplastic or neoplastic thyroid cells, where it irradiates and destroys the hyperfunctioning tissue as the iodine is incorporated into thyroid hormone. Unless large doses are administered, normal (i.e., nonadenomatous) thyroid tissue tends to be protected from the effects of radioiodine because it becomes atrophic and takes up very little of the administered dose of radioiodine.


When radioiodine is administered to a cat with hyperthyroidism, between 20% and 60% of the dose is taken up and accumulates in the thyroid tumor. The remainder is excreted primarily in the urine and to a lesser degree the feces. Radioiodine has a half-life of 8 days and emits both β-particles and γ-radiation. The β-particles, which cause 80% of the tissue damage, travel a maximum of 2 mm in tissue and have an average path length of 400 µm. Therefore β-particles are locally destructive to the thyroid tumor but spare adjacent atrophic thyroid tissue, parathyroid glands, and other cervical structures.



Patient Selection and Preparation before Radioiodine Treatment


Routine diagnostic testing generally should be performed by the referring veterinarian to determine if a cat is an appropriate candidate for this treatment. This is important because these cats tend to be middle-aged to older and therefore may have other geriatric problems unrelated to their hyperthyroidism. Cats should be relatively stable before being considered for radioiodine therapy. Those that have clinically significant or unstable cardiovascular, renal, gastrointestinal, endocrine (e.g., diabetes), or neurologic disease may not be very good candidates, especially because of the length of boarding required after the 131I treatment is administered.


The recommended pretreatment workup for hyperthyroid cats generally should include the following tests and procedures:



If concurrent renal disease is suspected or known to be present, many clinicians recommend evaluating medical management before a more definitive means of treatment such as radioiodine. In these cats, a low starting dose (i.e., 1.25 mg orally once daily) of methimazole with gradual dosage escalation is prudent, with monitoring (e.g., biochemical profile and total serum T4 determination) and dose adjustments done every 2 weeks. Once euthyroidism has been maintained for 2 to 4 weeks, no further fall in glomerular filtration rate (GFR) or acute worsening in renal function is expected, allowing one to decide whether to proceed with definitive therapy. Even if early chronic kidney disease (CKD) is uncovered during this methimazole trial, most cats remain good candidates for radioiodine treatment.


The veterinarian may choose to stabilize some cats for a few weeks or months before the time of referral for radioiodine treatment by administering cardiovascular medications, β-blocking agents, or antithyroid drugs or by feeding a low-iodine diet. Although concurrent use of antithyroid drugs or low-iodine diets does not interfere with radioiodine treatment, most treatment centers recommend that they be discontinued for at least 1 week before treatment with radioiodine. The main reason for this is to allow the cat to return to a hyperthyroid state by the time the radioiodine treatment is given; this ensures that the cat’s circulating thyroid-stimulating hormone (TSH) concentrations will be suppressed and that the 131I uptake by the nonadenomatous (i.e., normal) thyroid tissue and subsequent iatrogenic hypothyroidism will be minimized.


In some cats with life-threatening hyperthyroidism or concurrent disease (e.g., CKD), however, one may consider it best to continue treatment with antithyroid drugs until the cat is treated with radioiodine. Such cases must be discussed with the radioiodine treatment center before the referral.



Thyroid Scintigraphy for Evaluation of Hyperthyroid Cats


Thyroid scintigraphy provides valuable information regarding both thyroid anatomy and physiology and can play an integral role in the diagnosis, staging, and management of thyroid disease in cats. The procedure is extremely safe, does not require the use of anesthesia, and is cost-effective, especially when considering the costs of an incorrect diagnosis or inappropriate treatment.


The basis for this procedure is the unique physiology of the thyroid gland that results in the selective uptake of iodide by thyroid tissue. Although various isotopes of iodine are available for use in thyroid scintigraphy, their concurrent beta emission and associated local tissue damage (e.g., 131I) or greater expense (e.g., 123I) have limited their use in veterinary medicine. The pertechnetate ion has a similar size, molecular shape, and charge compared to iodide, which results in its uptake by thyroid tissue. The radionuclide technetium-99m pertechnetate (99mTcO4–) is a pure gamma emitter with a low photon energy (140 KeV) that makes it ideal for diagnostic imaging. Because of these properties, as well as the fact that 99mTcO4– is readily available and is relatively inexpensive, it has become the radionuclide of choice for routine thyroid imaging in veterinary medicine.


To perform thyroid imaging in cats, a small dose (3 to 4 millicuries [mCi]; 111 to 148 millibecquerel [mBq]) of 99mTcO4– is administered subcutaneously. Between 20 and 60 minutes later, the cats are laid on their abdomen (ventral view) or side (lateral view) while the gamma camera acquires the thyroid image. The scanning process itself usually takes less than a minute and generally does not require sedation.


In normal cats, the thyroid gland appears on thyroid scans as two well-defined, focal (ovoid) areas of radionuclide accumulation in the cranial to middle cervical region. The two thyroid lobes are symmetric in size and shape and are located side by side (Web Figure 21-1). On the scan, we expect the thyroid and salivary glands to be equally bright (a 1 : 1 brightness ratio). In addition to visual inspection, one can calculate the percent thyroidal uptake of radionuclide 99mTcO4– correlated with circulating thyroid hormone concentrations and provide an extremely sensitive means of diagnosing hyperthyroidism.



There are five reasons why thyroid scintigraphy should be considered in any cat with suspected hyperthyroidism.



1. First, thyroid scintigraphy helps confirm the diagnosis of hyperthyroidism, which is very useful in cats in which a thyroid nodule cannot be palpated. Because thyroid scintigraphy directly visualizes functional thyroid tissue and the “uptake” of the radioisotope can be estimated by determining the thyroid : salivary ratio, thyroid imaging can diagnose hyperthyroidism before laboratory tests are consistently abnormal (Web Figure 21-2). Thyroid scintigraphy is considered the gold standard for diagnosing mild hyperthyroidism in cats.



2. Thyroid scintigraphy can also exclude the diagnosis of hyperthyroidism in euthyroid cats that have false-positive elevations in their serum T4 or free T4 values. Studies of cats with nonthyroidal illness (e.g., diabetes; renal, gastrointestinal, or liver disease) have shown that between 6% and 12% of these cats have falsely high serum free T4 values, despite the fact that they are not hyperthyroid. In addition, routine screening of an apparently healthy senior cat occasionally reveals laboratory abnormalities that include slightly high total or free T4 concentrations, consistent with mild hyperthyroidism. As with sick cats with falsely high free T4 values, however, no thyroid nodule can be palpated in many of these cats and thyroid imaging may fail to confirm hyperthyroidism. Therefore not every cat with a high total T4 or free T4 value is truly hyperthyroid, and treatment for hyperthyroidism would be contraindicated.


3. In addition to visualization of functional cervical thyroid nodules, thyroid scintigraphy is an excellent method for evaluating the size of ectopic thyroid tissue, which can be located anywhere from the base of the tongue to the heart (Web Figures 21-3 and 21-4). In addition, thyroid images can locate large tumors that gravity has pulled into the thoracic cavity, which cannot be palpated on physical examination.




4. By providing a visual image of hyperfunctional thyroid tissue, thyroid scintigraphy allows for the determination of thyroid tumor mass or volume, which is useful in calculating each cat’s radioiodine dose. The goal of 131I therapy is to restore euthyroidism with a single dose of radiation without producing hypothyroidism. Recent research confirms that iatrogenic hypothyroidism contributes to the development of azotemia and shortened survival times in cats overtreated with radioiodine. To minimize the incidence of iatrogenic hypothyroidism, it is important to administer the lowest effective dose to each individual cat rather than giving a fixed dose of radioiodine to all cats. Again, thyroid scintigraphy provides an excellent method for evaluating the size of the hyperfunctional thyroid tissue, which aids in determining the proper dose to treat the individual hyperthyroid cat.


5. Thyroid scintigraphy also provides valuable information in the diagnosis and evaluation of hyperthyroid cats with thyroid carcinoma (Web Figure 21-5). Our latest studies suggest that, although thyroid carcinoma is rare in cats with recently diagnosed hyperthyroidism, the prevalence of carcinoma progressively increases in cats treated long term with antithyroid medications (Peterson and Broome, 2012a and 2012b). Of cats with more than 4 years of medical treatment, over 20% had scintigraphic evidence of thyroid carcinoma. The diagnosis of thyroid carcinoma can be challenging (even with histopathology), but without pretreatment scanning these cases would go undetected. Because of the large tumor volume associated with thyroid carcinoma, as well as the potential for local invasion and metastasis, most of these cats are treated with high doses of radioiodine (e.g., 30 mCi, 1100 mBq) in order to completely ablate all thyroid tissue, thereby curing the cat’s thyroid cancer (Web Figure 21-6).


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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Chapter 21: Radioiodine for Feline Hyperthyroidism

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