High-dose Radioiodine Treatment for Thyroid Carcinoma

Figure 1: Hyperthyroid cat with a huge thyroid tumor after 3 years of methimazole treatment. 
Notice the swollen neck, which turned out to be a massive thyroid carcinoma.

Thyroid carcinoma is a relatively rare cause of hyperthyroidism in cats (1-4). Our recent review of almost 2100 cats showed that less than 0.5% of cats with newly diagnosed hyperthyroidism will have thyroid cancer (5).

After months to years of methimazole treatment, it is not uncommon for the hyperthyroid cats' thyroid tumor(s) to continue to grow progressively larger (Fig. 1). Remember that all hyperthyroid cats have a thyroid tumor, which is responsible for the oversecretion of T4 and T3 (6,7).

In some of these cats, the thyroid tumor becomes very large (Fig. 1), and many of these will become difficult to regulate, even with high daily doses of oral or transdermal methimazole (8). Some cats eventually become completely refractory to methimazole or y/d, so alternative treatment modalities must be considered.

In addition to growing larger with time, the benign thyroid adenoma characteristic of early feline hyperthyroidism can also transform into malignant thyroid carcinoma in some cats (4,9,10). In our studies, the prevalence of thyroid carcinoma rises to over 20% in cats managed with methimazole longer than 4 years.

Again, methimazole or other antithyroid drug therapy (including Hill's y/d) does nothing to the thyroid tumor pathology and cannot stop the benign tumor from growing or transforming to carcinoma. Radioiodine therapy can be used to cure cats with such malignant thyroid tumors. Surgery can be attempted, but intrathoracic extension and metastasis is common, making it difficult to do a complete thyroidectomy these cats (Fig. 2).

Figure 2: Thyroid images of 6 hyperthyroid cats with thyroid carcinoma. 
Notice the large tumor volumes, with extension of disease beyond the limits of the thyroid capsule into the chest cavity in all cases.

High-dose Radioiodine Treatment for Thyroid Carcinoma

In cats with thyroid carcinoma, radioiodine offers the best chance for successful cure of the cancer because it concentrates in all hyperactive thyroid cells (i.e., carcinomatous tissue, as well as metastasis). Unlike cats with thyroid adenoma or adenomatous hyperplasia, the goal for cats with thyroid carcinoma is to totally ablate all thyroid tissue, ensuring complete destruction of all malignant thyroid tissue (Fig. 3).

Figure 3: Thyroid images of a hyperthyroid cat with thyroid carcinoma before and after high-dose radioiodine treatment.
Notice the complete ablation of all thyroid cancer tissue 2 months after treatment (right).

Because the tumor size and volume of thyroid carcinoma tissue is usually very large, extremely high doses of radioiodine (generally 10-fold higher than needed for most cats with benign thyroid disease) are almost always needed to destroy all of the malignant tissue. In most treatment centers that are licensed to treat with large doses of radioiodine, a high, fixed dose of 30 mCi (1110 mBq) is administered (4,11,12).

Longer periods of hospitalization are required with use of such high-dose radioiodine administration because of the prolonged radioiodine excretion. Because the goal is to ablate all thyroid tissue, this high dose almost always leads to iatrogenic hypothyroidism, necessitating daily L-thyroxine (L-T4) replacement therapy.

References:

1. Mooney CT, Peterson ME. Feline hyperthyroidism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:92-110. 
2. Baral R, Peterson ME. Thyroid gland disorders. In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders 2012;571-592. 
3. Peterson ME: Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
4. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. Journal of Feline Medicine and Surgery 2009;11:116-124.
5. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012; 26:754.
6. Peterson ME. Do all cats have a thyroid tumor? Is it thyroid cancer? Insights into Veterinary Endocrinology. May 7, 2011.
7. Gerber H, Peter H, Ferguson DC, et al. Etiopathology of feline toxic nodular goiter. Vet Clinics  North Am Small Anim Pract 1994;24:541-565
8. Peterson ME. Treatment of severe, unresponsive, or recurrent hyperthyroidism in cats. Proceedings of the 2011 American College of Veterinary Internal Medicine Forum. 2011;104-106.
9. Peterson ME, Broome MR. Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. Proceedings of European College of Veterinary Internal Medicine; 2012.
10. Peterson ME. Thyroid tumors grow progressively larger in most hyperthyroid cats treated with methimazole. Insights into Veterinary Endocrinology. August 26,2012.
11. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
12. Turrel JM, Feldman EC, Nelson RW, et al. Thyroid carcinoma causing hyperthyroidism in cats: 14 cases (1981-1986). J Am Vet Med Assoc 1988;193:359-364. 

Video of Hyperthyroid Cat Playing After Treatment

Gizmo is a Turkish Angora with hyperthyroidism whose owners brought him to Dr. Peterson's Hypurrcat treatment center. Dr. Peterson pioneered the radioiodine treatment for cats with hyperthyroidism. This video was taken after Gizmo was treated with radioiodine during his "photo shoot."

Gizmo came to us shaved (Turkish Angoras typically have long hair) due to the matting in his fur- failure to groom is a common symptom of long-haired cats with hyperthyroidism. As you can see from the video, cats treated at Hypurrcat enjoy all the comforts of home, and then some! We care for all animals as if they were our own.

For more info, please visit our website: www.animalendocrine.com

Estimating the Radioiodine Dose to Administer to Cats with Hyperthyroidism

Ideally, treatment of a hyperthyroid cat with a single dose of radioiodine should restore euthyroidism without inducing hypothyroidism. In other words, the goal of this treatment should be to irradiate and destroy all abnormal thyroid tissue (adenomatous or carcinomatous) but to leave the normal (nonadenomatous) thyroid tissue intact (1-4).

The optimal method for determining the amount of radioiodine required for effective treatment in cats remains somewhat controversial. Reported methods to determine the radioiodine dose for cats with hyperthyroidism are variable but can be divided into the following four general categories (4-9):

1. Fixed or “one size fits all” dosing
2. Individualized or “patient-specific” clinical scoring system for dose determination
3. Individualized, advanced clinical scoring system, with calculation of thyroid tumor volume and thyroid radionuclide uptake
4. High-dose I-131 treatment for thyroid carcinoma 

In this post, I'll discuss the first 3 of these dosing protocols. For my next post, I'll cover radioiodine treatment of feline thyroid carcinoma.

Fixed-dose radioiodine therapy
The fixed-dose approach, the most common method of treating hyperthyroid cats, assumes that most of these cats can be successfully treated by administering the same fixed, relatively high dose of radioiodine to all cats (i.e., 4 to 5 mCi [148 to 185 mBq]), regardless of the severity of hyperthyroidism or size of the thyroid tumor (4-6).

Because no effort is taken to determine thyroid tumor size or to estimate severity of hyperthyroidism, this dosing method is the easiest, involving no calculations and requiring little in the way of nuclear medicine equipment. However, to attain a reasonable success rate with this method, a large number of cats end up being either overdosed or underdosed with radioiodine.

For example, in my clinic, the median individualized dose given to our hyperthyroid cats is now 2.5 mCi (100 mBq), much less than the dosages administered with the fixed-dose approach. In my opinion,  a large number of cats treated using the fixed-dose method will receive too high of a radioiodine dose, exposing them to an unnecessary amount of radiation and greatly increasing the risk of iatrogenic hypothyroidism.  Since I do not use this method, I can't quote exact incidence, but I wouldn't be surprised if over 75% of these cats become hypothyroid.

On the other hand, a few cats with very large, benign thyroid adenomas that I treat in my clinic will require calculated radioiodine doses that are much higher (i.e., 6 to 12 mCi; 222 to 444 mBq) than those typically administered with the fixed-dose approach. These cats will likely be treatment failures and show persistent or recurrent hyperthyroidism with the fixed-dose approach.

So, although the fixed-dose method is the simplest to employ, the incidence of both long-term hypothyroidism and persistent hyperthyroidism are higher with this dosing method.

Individualized or “patient-specific” clinical scoring system for dose determination
In the second method of dose determination that I first described almost 20 years ago (7), the dose of radioiodine administered to hyperthyroid cats is determined by a clinical scoring system based on 3 factors that take into consideration the severity of clinical signs, the size of the cat's thyroid gland (determined by palpation of the goiter on physical examination), and the pretreatment serum T4 concentration. Using this scoring system, a low, medium, or relatively high 131-I dose is selected (4,7,8).

For example, cats with mild clinical signs, small thyroid tumor(s), and only a slightly high serum T4 concentration would receive smaller doses of radioiodine (e.g., 3 mCi; 111 mBq); cats with severe clinical signs, very large thyroid tumor(s), and markedly high serum T4 concentrations would receive high doses of radioiodine (i.e., 5 mCi; 185 mBq); and cats that lie between these extremes would receive intermediate doses of radioiodine (e.g., 4 mCi; 148 mBq).

In contrast to the fixed-dose method, the total radiation dosage delivered to the cats with mild hyperthyroidism is lower and, thus, the prevalence of iatrogenic hypothyroidism is minimized. However, even with this scoring system, many cats develop low serum T4 values after treatment and some cats, especially those with severe disease, are not cured with a single dose of radioiodine.

Individualized, modified, clinical scoring system, with calculation of thyroid tumor volume and thyroid radionuclide uptake
In the third method that I now use, the dose of radioiodine administered is based on a refinement of the scoring system outlined above (4). Again, this refined scoring system takes into consideration the severity of the cat’s clinical signs, the size of thyroid tumor, and the pretreatment serum T4 and T3 concentrations. In addition, however, thyroid imaging is used to better estimate the volume of the thyroid tumor tissue, and the thyroid radionuclide uptake is determined (9-11). The dose of radioiodine is then calculated from these measurements.

Using this protocol, very low doses of radioiodine (e.g., < 2 mCi; <75 mBq) will result in the cure of many cats with early hyperthyroidism that have small but hyperfunctional thyroid tumors on thyroid imaging. These radioiodine doses are much lower than the lowest dose given with the original scoring system (3 mCi; 111 mBq) or used with the fixed-dose methods (4-5 mCi; 148-185 mBq).

In contrast, other cats with severe hyperthyroidism and large volumes of autonomously functional thyroid tissue (but without scintigraphic evidence of malignancy) may require up to 15 mCi (555 mBq) of 131-I to restore euthyroidism. These calculated radioiodine doses are much higher than the highest dose given with the original scoring system (5 mCi; 185 mBq) or used with the fixed-dose methods (4-5 mCi; 148-185 mBq).

Botton Line:

I believe that determining the thyroid tumor volume and percent 131-I uptake play key roles in calculating the best 131-I dose needed to completely ablate all tumor tissue but preserve any remaining normal thyroid tissue.

Physical palpation of the thyroid gland may yield equivalent information to that obtained from the thyroid scan in some cats, especially those with smaller, easily palpated nodules (7). However, the thyroid tumor volume will likely be greatly underestimated in cats with substernal or ectopic goiters based on physical evaluation alone, especially when those thyroid nodules cannot be palpated (4,11).

It is clear that we can achieve much better results (less hypothyroidism or persistent hyperthyroidism  with use of an individualized dosing protocols. However, a percentage of hyperthyroid cats, especially those with long-standing, severe hyperthyroidism, will not have enough "normal" residual thyroid tissue left to maintain euthyroidism after we successfully ablate all of the thyroid tumor tissue. In those cats, mild to moderate degrees of iatrogenic hypothyroidism will result, no matter what dosing protocol is used.

In my opinion, curing the hyperthyroidism with radioiodine or surgery remain the ideal treatment options for cats. Even if the cat needs thyroid hormone supplementation, definitive treatment with either radioiodine or surgery still remain a better option than long-term medical or nutritional management.  Without definitive treatment, the thyroid tumors remain and will continue to grow, and may potentially transform into thyroid carcinoma and metastasize (12).

References:

1. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
2. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. Manual of Canine and Feline Endocrinology Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
3. Peterson ME. Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
4. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
5. Meric SM, Rubin SI. Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989). J Am Vet Med Assoc 1990;197:621-623. 
6. Craig A. A prospective study of 66 cases of feline hyperthyroidism treated with a fixed dose of intravenous 131-I. Aust Vet Practit 1993;23. 
7. Peterson ME, Becker DV. Radioiodine treatment of 524 cats with hyperthyroidism. J Am Vet Med Assoc 1995;207:1422-1428.  
8. Peterson ME. Radioiodine treatment of hyperthyroidism. Clin Tech Small Anim Pract 2006;21:34-39. 
9. Forrest LJ, J. BC, Metcalf MR, et al. Feline hyperthyroidism: efficacy of treatment using volumetric analysis for radioiodine dose calculation. Vet Radiol Ultrasound 1996;37:141-145. 
10. Broome MR, Turrel JM, Hays MT. Predictive value of tracer studies for 131-I treatment in hyperthyroid cats. Am J Vet Res 1988;49:193-197.
11. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clin Tech Small Anim Pract 2006;21:10-16. 
12. Peterson ME, Broome MR: Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. J Vet Intern Med 20112: 26:1523.

Updated Vetsulin Insulin Approved For Release in USA

Merck Animal Health announced last week that Vetsulin (porcine insulin zinc suspension) will again be available for distribution in the USA (1). This is welcome news, especially for dogs with diabetes mellitus that are not be well regulated with other available insulin preparations, such as human recombinant NPH. Most authorities consider Vetsulin, known as Caninsulin outside the USA (2), to be the initial insulin of choice for treatment of dogs with diabetes mellitus (3-6). It can also be used to successfully cats with diabetes (7,8), but we have many other good options for treatment of feline diabetes.

As you may know, Vetsulin has had its share of problems of the last few years, which lead to the FDA having it withdrawn from the US market. All of these manufacturing issues have been resolved and the FDA has re-approved the drug for release.

How is the "new" Vetsulin different than the original insulin product?

According to the company, the updated Vetsulin product has the same characteristics as the original insulin preparation, and the action in diabetic patients is expected to be the same as before. There have been no changes in the safety profile of Vetsulin for use in either dogs or cats.

The only difference in the Vetsulin itself is a slight change in the listed proportion of the short-acting amorphous fraction and long-acting crystalline fraction. The short-acting amorphous fraction is now listed as 35% (it was 30%), whereas the long-acting crystalline fraction is now listed as 65% (it was 70%).  See my discussion below, where I discuss why this listed proportion in the short-and long-acting insulin fractions has been changed.

Vetsulin will now be available only in 10-ml vials. The 2-5 ml vial formulation of Vetsulin has been discontinued.

Two important differences in the updated in Vetsulin Package Insert: (9)

1. Prior to use, vials of Vetsulin should be shaken thoroughly (manually) until a homogeneous, uniformly, milky suspension is obtained. Foam on the surface of the suspension formed during shaking should be allowed to disperse before the product is used.
2. Vetsulin contents should be used within 42 days after the vial is first punctured.  

For the first new vials of Vetsulin that are released, the initial product dating will be only 12 months from the manufactured date. The company expects that Vetsulin will eventually have a 24-month shelf-life.

Additional information can be found on the Veterinary Home Page under Product Update section (10). Also, see the package insert for full information regarding contraindications, warnings, and precautions (9).

Bottom line:

It's great to have Vetsulin, an FDA-approved insulin for use in both dogs and cats, back on the market. The company has done a great deal of work showing that Vetsulin is stable and effective, and they have made a few minor but good improvements in this insulin preparation.

Vigorous manual shaking of the Vetsulin? How will that impact accurate dosing?
We have all been taught that vigorous shaking will interfere with accurate dosing because of air bubbles that form when the insulin bottle is shaken (5,11). When the dose is drawn up, the insulin suspension may come out into the syringe together with lots of air bubbles.  In addition, we tend to worry that too vigorous shaking may damage the insulin protein structure itself. For these reasons, we generally instruct owners to gently roll the insulin vial than that vigorously shake it!

According to the company, the instructions are now are to give the Vetsulin bottle a a vigorous shake on initial use; then let it settle for a few minutes to let the bubbles rise before drawing up the dose. Upon subsequent insulin dosing, the bottle should only need a quick shake (less vigorous) to resuspend the insulin prior to drawing up the insulin dose.

Why this difference in vigorous shaking vs. rolling? I don't know, but I suspect it has sometime to do with the way the study was designed and input from the FDA. In any case, Merck Animal Health actually has done the studies to prove that this vigorous manual shaking does not interfere with the measured insulin concentration in the product (10).

Why was the proportion in the short-and long-acting insulin fractions changed? 
According to the company, the proportions of the short-acting amorphous fraction and long-acting crystalline fraction have not actually changed, as compared to the original Vetsulin product. Instead, the new stated ratio (65% long-acting and 35% short-acting insulin) represents a more accurate reflection of the actual composition of both the original and updated Vetsulin product (10).

Nevertheless, on a clinical basis, such a small change in the short- vs. the long-acting insulin fractions would not be expected to make any difference in the animal's glycemic control, even if the composition of the product did change slightly.

Must Vetsulin really be discarded after only 42 days? 
The Vetsulin product insert (9) clearly states that the product should be used within "42 days of first vial puncture."

Has the has efficacy really been determined to decrease after 42 days?  The answer to that is no — it's almost certain that the potency of this preparation will extend many days (or even weeks) longer than this 42 days.  However, because Merck Animal Health only did the FDA studies for a period of 42 days, that's what they have been required to put on the package insert. But remember, in addition to efficacy, we must also worry about bacterial contamination secondary to repeated puncture of the insulin vial (11).

Why such a short expiration date? 
Again, for the first new vials of Vetsulin that are released, the initial product dating will be only 12 months from the manufactured date. This is not because the updated Vetsulin is unstable, but the FDA requires ongoing studies of the insulin's duration. The company expects that Vetsulin will eventually have a 24-month shelf-life (10).

Since we do not have to worry about Vetsulin disappearing again, at least anytime soon, I wouldn't recommend purchasing too many insulin vials now, since the initial "expiration" date will be only a few months.

References:

1. Vetsulin website. www.vetsulin.com
2. Caninsulin website. www.caninsulin.com
3. Monroe WE, Laxton D, Fallin EA, et al. Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs. J Vet Intern Med 2005;19:675-682. 
4. Fleeman LM, Rand JS, Morton JM. Pharmacokinetics and pharmacodynamics of porcine insulin zinc suspension in eight diabetic dogs. Vet Rec 2009;164:232-237. 
5. Nelson RW. Canine diabetes mellitus In: Ettinger SJ,Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Seventh Edition ed. St. Louis: Saunders Elsevier, 2010;1449-1474.
6. Davison LJ. Canine diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;116-132.
7. Michiels L, Reusch CE, Boari A, et al. Treatment of 46 cats with porcine lente insulin—a prospective, multicentre study. J Feline Med Surg 2008;10:439-451. 
8. Martin GJ, Rand JS. Control of diabetes mellitus in cats with porcine insulin zinc suspension. Vet Rec 2007;161:88-94. 
9. Vetsulin Package Insert. www.vetsulin.com/PDF/Vetsulin-Package-Insert.pdf
10. Vetsulin website: Veterinary Product Updates. www.vetsulin.com/vet/Product_Update.aspx
11. American Diabetes Association. Insulin administration. Diabetes Care 2001;24:1984-1987. 

Thyroid Scintigraphy for Diagnosis and Staging of Cats to be Treated with Radioiodine

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 (1-5). 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.

What radiosotopes are used for thyroid imaging?
The basis for this procedure is the unique physiology of the thyroid gland that results in the selective uptake of iodide by thyroid tissue (4-7). Although various isotopes of iodine are available for use in thyroid scintigraphy, their concurrent beta emission and associated local tissue damage (e.g., 131-I) or greater expense (e.g., 123-I), 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 (99m-TcO4) is a pure gamma emitter with a low photon energy (140 KeV) that makes it ideal for diagnostic imaging (4-7). Because of these properties, as well as the fact that technetium is relatively inexpensive, it has become the radionuclide of choice for routine thyroid imaging in veterinary medicine.

How a thyroid scan is performed in cats
To perform thyroid imaging in cats, a small dose (3-4 millicuries of  technetium is administered subcutaneously. Between 20 to 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 (4-6).

Fig 1: Thyroid scintigraphy
in a normal cat

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 (Figure 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, we can calculate the percent thyroidal uptake of the radioactive tracer or the thyroid:salivary ratio. Both of these calculations are strongly correlated with circulating thyroid hormone concentrations and provide an extremely sensitive means of diagnosing hyperthyroidism (4-9).

5 reasons why a thyroid scan is performed
There are five reasons why thyroid scintigraphy should be considered in any cat with suspected hyperthyroidism, especially before radioiodine treatment.

Reason 1— First, thyroid scintigraphy helps confirm the diagnosis of hyperthyroidism, which is very useful in cats in which a thyroid nodule cannot be palpated (4-9). 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 (Figure 2). Thyroid scintigraphy is considered the gold standard for diagnosing mild hyperthyroidism in cats.

Fig 2: Thyroid imaging in 2 cats with mild hyperthyroidism. The cat on the left has a unilateral thyroid adenoma, whereas the cat on the right has bilateral adenomas. In both cats, notice that the uptake of the radionuclide by the thyroid adenoma(s) is higher than the uptake by the cats' salivary tissue.

Reason 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 (10,11).

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 (12). 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.

Fig 3: Ectopic thyroid adenoma
in the chest cavity of a hyperthyroid cat

Reason 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 (Figure 3).

In addition, thyroid images can locate large tumors that gravity has pulled into the thoracic cavity, which cannot be palpated on physical examination (4-9).

Reason 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 (6,12,13). The goal of 131-I 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 (14). 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 (12). 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.

Reason 5—Thyroid scintigraphy also provides valuable information in the diagnosis and evaluation of hyperthyroid cats with thyroid carcinoma (Figure 4). Our recent 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. Of cats treated for longer than 4 years with medical treatment, over 20% had scintigraphic evidence of thyroid carcinoma (15).

Fig 4: Thyroid images of 6 hyperthyroid cats with thyroid carcinoma. Notice the large tumor volumes, with extension of disease beyond the limits of the thyroid capsule into the chest cavity in all cases.

The diagnosis of thyroid carcinoma can be challenging (even with histopathology) but without pre-treatment 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) in order to completely ablate all thyroid tissue (12), thereby curing the cat’s thyroid cancer (Figure 5).

Fig 5: Thyroid images of a hyperthyroid cat with thyroid carcinoma before and after high-dose radioiodine treatment.
Notice the complete ablation of all thyroid cancer tissue 2 months after treatment (right).

Is a thyroid scan mandatory in all cats treated with radioiodine?
No, a thyroid scan is not absolutely mandatory — most treatment facilities in the USA do not do thyroid imaging prior to treatment.

Despite the valuable information obtained by performing thyroid scintigraphy, it is not required prior to radioiodine therapy, just as thoracic radiographs are not required prior to amputating a limb in a patient with a primary bone tumor or a preanesthetic laboratory screening is not required prior to dental prophylaxis or other elective procedures requiring anesthesia. Nevertheless, use of thyroid scintigraphy is considered good medicine because the findings can and do result in modification of the therapeutic dose, aid in the diagnosis of hyperthyroidism, and provide prognostic information.

References:

1. Mooney CT, Peterson ME: Feline hyperthyroidism, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; 199-203.
2. Baral R, Peterson ME: Thyroid gland disorders, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, 2012;571-592.
3. Peterson ME: Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
4. Peterson ME, Becker DV. Radionuclide thyroid imaging in 135 cats with hyperthyroidism. Veterinary Radiology 1984;25:23-27. 
5. Daniel GB, Brawnier WR. Thyroid scintigraphy In: Daniel GB,Berry CR, eds. Textbook of Veterinary Nuclear Medicine. 2nd ed. Harrisburg, PA: American College of Veterinary Radiology, 2006;181-199.
6. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21,10-16. 
7. Feeney DA, Anderson KL. Nuclear imaging and radiation therapy in canine and feline thyroid disease. Vet Clin North Am Small Anim Pract 2007;37:799-821, viii. 
8. Harvey AM, Hibbert A, Barrett EL, et al. Scintigraphic findings in 120 hyperthyroid cats. J Feline Med Surg 2009;11:96-106. 
9. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012;26:754.
10. Mooney CT, Little CJ, Macrae AW. Effect of illness not associated with the thyroid gland on serum total and free thyroxine concentrations in cats. J Am Vet Med Assoc 1996;208:2004-2008. 
11. Peterson ME, Melian C, Nichols R. Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc 2001;218:529-536
12. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
13. Volckaert V, Vandermeulen E, Saunders JH, et al. Scintigraphic thyroid volume calculation in hyperthyroid cats. J Feline Med Surg 2012;14:889-894. 
14. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 2010;24:1086-1092. 
15. Peterson ME, Broome MR:  Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. J Vet Intern Med 26:1523,2012.

Radioiodine Treatment in Cats: Patient Selection and Preparation

Routine diagnostic testing should always be performed by the primary-care veterinarian before referral for radioiodine treatment to determine if a cat is an appropriate candidate for this treatment (1-4). This is very important, inasmuch as these cats tend to be middle-aged to older and therefore may have other geriatric problems unrelated to the cat's 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 for this treatment, especially because of the length of boarding required after the 131-I dose is administered to the cats.

Working up the hyperthyroid cat—Recommended testing for diagnosis and staging of the disease

In any cat with suspected hyperthyroidism, we have 2 goals in diagnostic testing (1-4):

1. Our primary goal is to make a definitive diagnosis of hyperthyroidism, This may not be as easy as cat owners or veterinarians may believe. None of the current thyroid function tests are prefect, and false-positive test results are not uncommon.
2. Our second goal is to exclude other problems (kidney disease, gastrointestinal disease, diabetes), all common in the middle-aged to older cat. In some hyperthyroid cats, these concurrent problems are more important than the hyperthyroidism itself and must be addressed immediately.

To acheive these two goals, the recommended pretreatment workup for hyperthyroid cats includes the following tests and procedures (5):

• Routine database, including a complete blood count (CBC), serum chemistry panel, and complete urinalysis.
• Pretreatment or untreated serum total T4 concentration (with the cat not on antithyroid drug treatment or a low-iodine diet).
• If the cat has been treated medically or nutritionally for longer than 1 to 2 months, the antithyroid medication or low-iodine diet may have to be discontinued for 5 to 7 days and another serum total T4 measured to determine the true severity of the cat's hyperthyroidism. 
• If hyperthyroidism is mild or a thyroid nodule cannot be palpated, a complete thyroid panel is recommended to help confirm hyperthyroidism. This includes determination of serum concentrations of total T4, free T4, total T3, and thyroid-stimulating hormone (TSH).  Untreated hyperthyroid cats generally have high total T4, free T4, or T3 levels, whereas serum TSH is almost always suppressed to undetectable concentrations (6-8).
• Chest radiography or cardiac ultrasonography (or both) should be performed if the cat has evidence of any clinically significant cardiac disease (especially pronounced heart murmur, arrhythmia, dyspnea, or jugular venous distention).
• If severe gastrointestinal signs are present (e.g., poor appetite, severe vomiting or diarrhea), an abdominal ultrasound should be done to help rule out other problems not related to hyperthyroidism.

Hyperthyroidism and kidney disease

If concurrent renal disease is suspected or known to be present, many recommend evaluating medical management before a more definitive means of treatment such as radioiodine (1-3,9). In these cats, a low starting dose (i.e., 1.25 mg orally once daily or divided twice 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 or mild chronic kidney disease (CKD) is uncovered during this methimazole trial, most cats remain good candidates for radioiodine treatment (10).  Remember that hyperthyroidism contributes to the development of the renal disease seen in hyperthyroid cats so control of the hyperthyroidism may help slow the progression of the concurrent kidney disease (11).

Stabilizing the cat 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 β-blocking agents (e.g., atenolol), L-carnitine, antithyroid drugs (e.g., methimazole or carbimazole), or by feeding a low-iodine diet (Hill's y/d) (1-3).

Although concurrent use of antithyroid drugs or low-iodine diets does not "interfere" with radioiodine treatment, we recommend that they be discontinued for at least 1-2 weeks before treatment with radioiodine. The main reason stopping the antithyroid drug treatment or the low-iodine diet 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 TSH concentrations will be suppressed and that the 131-I uptake by the nonadenomatous (i.e., normal) thyroid tissue and subsequent iatrogenic hypothyroidism will be reduced (12).  Remember that the thyroid adenoma(s) does not need circulating TSH to take up and concentrate the radioiodine.

In contrast, β-blocking agents (e.g., atenolol) or other cardiac medication will not interfere with the radioiodine treatment and can be given up to, and even during, the hospitalization period as needed.

Less commonly, L-carnitine is used to help ameliorate hyperthyroid clinical signs in hyperthyroid cats; the primary effect of this drug is to inhibit the effect of T4 and T3 on the peripheral tissues rather than work on the thyroid gland itself (13). Although L-carnitine may reduce symptoms of hyperthyroidism, it does not change circulating thyroid hormone concentrations or reduce thyroid tumor volume or size. Like the β-blocking agents, L-carnitine does not interfere with the radioiodine treatment and can be given up to, and even during, the hospitalization period.

References:

1. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
2. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. Manual of Canine and Feline Endocrinology Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
3. Peterson ME. Hyperthyroidism in cats In: Rand JS, Behrend E, Gunn-Moore D, et al., eds. Clinical Endocrinology of Companion Animals. Ames, Iowa Wiley-Blackwell, 2013;295-310.
4. Kintzer PP. Considerations in the treatment of feline hyperthyroidism. Vet Clin North Am Small Anim Pract 1994;24:577-585. 
5. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD,Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
6. Peterson ME, Melian C, Nichols R: Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc 2001;218:529-536.
7. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34. 
8. Peterson ME. Diagnostic testing for hyperthyroidism in cats: more than just T4. Journal of Feline Medicine and Surgery 2013:In press. 
9. Trepanier LA. Medical management of hyperthyroidism. Clin Tech Small Anim Pract 2006;21:22-28. 
10. Peterson ME. Treatment of hyperthyroidism and concurrent renal disease: is the "Tapazole trial" necessary? Conference Proceedings 29th Annual Veterinary Medical Forum (American College of Veterinary Internal Medicine) 2011;104-106. 
11. Syme H. A common duo: Hyperthyroidism and chronic kidney disease. NAVC 2013. 2. Syme HM. Cardiovascular and renal manifestations of hyperthyroidism. Vet Clin North Am Small Anim Pract 2007;37:723-743, vi. 
12. Fischetti AJ, Drost WT, DiBartola SP, et al. Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats. Vet Radiol Ultrasound 2005;46:267-272. 
13. Peterson ME. Alternative medical treatments for hyperthyroid cats. Conference Proceedings North American Veterinary Conference (NAVC) Conference 2012: Small Animal & Exotics Proceedings 2012;852-858.

My other related blog posts:

• Diagnosing Hyperthyroidism in Cats: Routine Testing Procedures 
• Diagnosis of Hyperthyroidism in Cats: Serum T4 Concentrations 
• Diagnosis of Hyperthyroidism in Cats: Serum T3 Concentrations 
• Diagnosis of Hyperthyroidism in Cats: Serum Free T4 Concentrations 
• Diagnosis of Hyperthyroidism in Cats: Serum Free T4 (Part 2) 
• Diagnosis of Hyperthyroidism in Cats: Serum TSH Concentrations 
• Treatment Options and Considerations for Hyperthyroid Cats 
• Treating Cats with Hyperthyroidism: Antithyroid Drugs 
• How to Dose and Monitor Hyperthyroid Cats on Methimazole 
• Alternative Medical Treatments for Hyperthyroid Cats 

Podcast: Increasing Rates of Obesity in Our Cats and Dogs

We love our pets. But sometimes, when it comes to rewarding them with treats and food, we might love them a little too much. As a result, our pets are increasingly overweight and obese.

To help quantify just how serious this issue has become, the Association for Pet Obesity Prevention (for which Dr. Peterson serves as a board member) conducts annual surveys on obesity in U.S. pets. Just last week, the group released its 6th annual survey.

In the latest AVMA Animal Tracks podcast, Dr. Ernie Ward, founder of APOP, discusses this year's results. To here the podcast, click this link.

For more information about the 2012 National Pet Obesity survey results or the Association for Pet Obesity Prevention in general, please visit their website at www.petobesityprevention.com.