What's the Expected Time for Signs of Feline Hyperthyroidism to Resolve after Treatment?

My 16-year old cat was recently treated with radioiodine (I-131) for his severe hyperthyroidism. How long after radioiodine treatment will the thyroid values normalize and the symptoms of the hyperactive thyroid begin to resolve so he feels better? 

My cat lost about half of his body weight, much of it in muscle mass. Will his wasted muscles ever return to normal? If so, when can I expect to see improvement?

My Response: 

You have asked two good questions, which, on the surface seem simple enough to answer. The answers to "how long for clinical signs to resolve" however, depend on a number of factors. I'll do my best to explain why it's not possible for me to give you the definitive answers you want.

How long does it take for serum thyroid hormone levels to normalize after I-131?
Depending on the dosing protocol used, about 90% of cats will have serum thyroid hormone concentrations (e.g., T4 and T3) within reference range limits by 30 days after I-131 treatment. Most of the remaining cats will show a nice drop in T4 and T3 levels when rechecked in a month, but it will take longer to for their thyroid hormone concentrations to completely normalize.

In general, the full extent of the radioiodine treatment will be evident by 3 months after treatment, although a few cats continue to show even more (minor) improvement when rechecked at 4 to 6 months.

As the thyroid values normalize, the clinical signs we see also gradually resolve. Some signs, such as nervousness or rapid heart rate, generally resolve fairly quickly, whereas other signs, such as marked weight loss and muscle wasting, obviously take much longer.

How fast do we want the serum thyroid values to fall after radioiodine treatment?
My goal in treating hyperthyroid cats with radioiodine is to gradually normalize the high serum thyroid hormone concentrations— not lower the values too quickly. I'd rather that the thyroid values fall slowly over the first month after treatment, allowing the rest of the body to gradually get used to being euthyroid once again. This is especially true in cats with concurrent kidney disease, when a drastic fall in thyroid values can aggravate the serum kidney values and can even lead to severe renal failure.

To achieve this gradual fall in the high serum thyroid hormone levels, I administer the smallest dose necessary to cure the hyperthyroidism. By giving individualized, lower doses of radioiodine, we can also reduce the incidence of post-treatment hypothyroidism (underactive thyroid condition) in these cats.

How often does the radioiodine fail to cure the hyperthyroidism?
About 5% of cats that I treat will remain slightly hyperthyroid at the 3-month follow-up period. Many treatment facilities will claim a higher rate of cure (98-100%) than I do, which is made possible by administering higher doses of radioiodine to their cats. In addition to decreasing the incidence of persistent hyperthyroidism, the use of higher radioiodine doses will also hasten the rate of decline in the serum thyroid hormone concentrations.

So why not use this high-dose I-131 protocol instead of my lower-dose approach? Simple — the downside of administering higher radioiodine doses is that this method will lead to a higher rate of iatrogenic hypothyroidism as both the thyroid tumor, as well as most normal thyroid tissue, are irradiated and destroyed (1,2). As I've previously discussed (see my post, Estimating the Radioiodine Dose to Administer to Cats with Hyperthyroidism), more that 30% of cats will become hypothyroid using the standard high-dose treatment protocol, but this incidence could in fact be much higher, possibly up to 75%.

Diagnosing iatrogenic hypothyroidism
To monitor for iatrogenic hypothyroidism, we routinely run a serum thyroid panel (i.e., total T4, T3, free T4, and TSH) at 1 and 3 months after treatment (2,3). Most facilities recommend monitoring just the total T4 concentration, but this is not adequate for monitoring since many hypothyroid cats will maintain a low-normal total T4 value, despite being hypothyroid.  Based on our studies, it's becoming increasing clear that feline hypothyroidism can only be diagnosed by finding low to low-normal T4 and T3 values in conjunction with high TSH values.

Restoring lost body weight and muscle mass
Once euthyroidism is reestablished, most cats will gain weight within a few weeks (certainly by 2-3 months). If marked muscle wasting has occurred, it may not be possible to completely regain the lost muscle. Remember that it will help to feed a diet that's higher in protein (40-50% of calories), higher in fat (40-50% of calories), and relatively low in carbs (less than 15% of calories) (4). For more information, check out my post on The Best Diet to Feed Hyperthyroid Cats.

References:

1. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2014.
2. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compend Contin Educ Vet 2013;35:E4. 
3. Peterson ME. Diagnosis and management of iatrogenic hypothyroidism In: Little SE, ed. August's Consultations in Feline Internal Medicine: Elsevier, 2014;in press.
4. Peterson ME. Nutritional management of endocrine disease in cats. Proceedings of the Royal Canin Feline Medicine Symposium 2013;23-28.

Related Blog Posts:

• Peterson ME. How Does Radioiodine Really Work to Treat Hyperthyroidism? Insights into Veterinary Endocrinology blog.  July 12, 2012.
• Peterson MEL Estimating the Radioiodine Dose to Administer to Cats with Hyperthyroidism. Animal Endocrine Clinic blog. April 30, 2013.
• Peterson ME. Success Rates for Radioiodine Treatment in Hyperthyroid Cats. Animal Endocrine Clinic blog. May 24, 2013.
• Peterson ME. The Best Diet to Feed Hyperthyroid Cats. Insights into Veterinary Endocrinology blog. September 13, 2011

Transient Hypothyroidism in Cats Following Radioiodine

Transient hypothyroidism, with the development of subnormal thyroid hormone levels, is common after radioiodine therapy. However, such suppression in the circulating thyroid hormone concentrations is usually mild and generally does not require thyroid hormone replacement therapy.

Why Transient Hypothyroidism Develops after I-131 Treatment

Prior to treatment of a hyperthyroid cat, the high circulating levels of the thyroid hormones (T3 and T4) have a negative feedback effect on the pituitary gland to suppress thyroid stimulating hormone (TSH) release (1-4). Therefore, serum TSH concentrations in hyperthyroid cats fall to low or undetectable levels (Figure 1).

Fig. 1: In normal cat, normal levels of thyroid hormone (T4 and T3) are controlled by TSH, a hormone secreted by the pituitary gland. In hyperthyroid cats, their thyroid tumor(s) secrete too much T4 and T3, resulting in a decrease in pituitary TSH secretion. Without adequate amounts of circulating TSH, any remaining normal thyroid tissue stops working and will atrophy.

Since adequate amounts of circulating TSH are needed by normal thyroid tissue for both iodine uptake and thyroid hormone secretion, the decreased circulating TSH concentrations that accompany persistent hyperthyroidism lead to atrophy of the normal (nonadenomatous) thyroid tissue (Figures 1 & 2). In contrast, because the adenomatous thyroid nodules (thyroid tumors) are autonomous and do not require circulating TSH for iodine uptake or thyroid hormone secretion, these thyroid tumors continue to exhibit both growth and hyperfunction (Figure 2).

See the thyroid scans below (Figure 2), which illustrate how cats with a thyroid adenoma affecting only 1 of the 2 thyroid lobes will show complete suppression of the normal lobe and not take up any radioactivity (labeled Unilateral, left panel). In contrast, the cats in the middle and right panels have both thyroid lobes involved with tumor (5).

Fig. 2: Thyroid scans in 3 hyperthyroid cats. All had low serum TSH concentrations. In the cat with a unilateral thyroid adenoma (left panel), the normal thyroid lobe is not visible — it has stopped functioning properly and has atrophied as a result of the low circulating TSH concentrations.

Many cats treated with radioiodine go through a period of transient, mild hypothyroidism after the 131-I treatment has destroyed their thyroid tumor(s). When rechecked within the first month after radioiodine therapy, many hyperthyroid cats have low to low-normal serum T4 concentrations (Figure 3).

If not overdosed with radioiodine, almost all these cats have some remaining “normal” thyroid tissue surrounding the thyroid tumor tissue, which has been chronically suppressed by the hyperthyroid state. However, now that the hyperthyroidism has been cured, pituitary TSH secretion eventually recovers and serum TSH concentrations will rise, resulting in stimulation of any remaining normal, but previously dormant, thyroid tissue.

Fig. 3: In hyperthyroidism,  the high T4 and T3 levels suppress pituitary TSH secretion to very low levels. Once the thyroid tumor is irradiated and destroyed, the T4 and T3 levels will fall to normal or even low levels for 1-2 months. With time, however, the pituitary gland recovers and starts to secrete TSH once again (sometimes to higher-than-normal amounts for a time). This allows any remaining normal thyroid tissue to become active once again and secrete normal amounts of thyroid hormone.

Most cats with a sufficient volume of normal thyroid tissue regain the ability to produce adequate amounts of thyroid hormone to maintain euthyroidism within 3 months of radioiodine therapy. Rarely, cats require as long as 6 months of chronically increased endogenous TSH levels to recover lost thyroid function and regain the ability to maintain normal thyroid hormone levels.

Bottom Line
Since transient hypothyroidism is common and and most cats will recover normal thyroid function with time, L-T4 replacement is not generally indicated at the time of this early recheck period.

However, if evidence of new or worsening kidney disease is found, short-term or permanent L-T4 replacement may be indicated to help preserve any residual renal function and prevent irreversible renal injury. I'll be discussing more about hypothyroidism and kidney function in a upcoming post.

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. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clin Tech Small Anim Pract 2006;21:10-16. 

Success Rates for Radioiodine Treatment in Hyperthyroid Cats

The ideal goal of radioiodine (131-I) therapy in cats with hyperthyroidism is to restore euthyroidism with a single dose of radioiodine without producing hypothyroidism. Indeed, most hyperthyroid cats treated with 131-I are cured by a single dose (1-7).

Recommended monitoring after radioiodine
In general, the cats should be monitored at 2 to 4 weeks and again at 3 months after discharge from the radioiodine facility (4,7). At both of these recheck times, a complete physical examination as well as routine laboratory testing (e.g., CBC, serum chemistry panel, urinalysis) and serum thyroid hormone determinations (i.e, a total T4 concentration at minimum) are recommended.

If the serum T4 falls to subnormal or low-normal values (< 1.5 µg/dl) and iatrogenic hypothyroidism is suspected, a complete thyroid profile (total and free T4, T3, cTSH concentrations) is recommended to help rule out that diagnosis (4,8). I'll be discussing transient and permanent hypothyroidism more in my upcoming posts.

Cure rate after radioiodine
Serum thyroid hormone concentrations are normal within 2 to 4 weeks of radioiodine treatment in approximately 85% of cats and in 95% of cats by 3 months (5,6). Although cats appear to feel better within days after treatment, the owner should notice gradual clinical improvement and resolution of the signs of hyperthyroidism during this 3-month period.

Note that these percentages indicate remission of the hyperthyroid state but do not reflect the incidence of iatrogenic hypothyroidism, which has a reported incidence as high as 30% in some studies (9). Other studies, which employ serum TSH values to help identify early hypothyroidism, indicate that the rate of hypothyroidism can be much higher (up to 80%), depending on the method of dose determination. (10).

Persistent hyperthyroidism—Causes of treatment failure 
Approximately 5% of cats fail to respond completely and remain hyperthyroid after treatment with radioiodine. In studies from my clinic, most cats with persistent hyperthyroidism have large thyroid tumors, severe hyperthyroidism, and very high serum T4 concentrations (11). Other cats with mild-to-moderate hyperthyroidism may have a lower-than-expected thyroid 131-I uptake or show rapid turnover of the administered 131-I by the thyroid tumor (see below). In all these instances, treatment failure results because the radiation dose delivered to the tumor was inadequate to completely ablate the adenoma.

During the first 3 to 5 days of treatment with 131-I, we routinely measure daily neck radiation levels as an approximation of the cat’s thyroid iodine uptake value. This is useful in estimating the 131-I residence time in the thyroid tumor and can help determine the cause of treatment failure. In most hyperthyroid cats, the maximal thyroid radiation level is reached between 24 and 48 hours. 

Occasionally, a hyperthyroid cat shows an early peak thyroid uptake reading (i.e., sooner than 24 hours after dose administration), with lower thyroid uptake values at 24 and 48 hours. This early peak thyroid radioiodine uptake with rapid clearance is defined as “rapid iodine turnover” by the thyroid tumor (12). Such rapid turnover implies a short residence time for 131-I in the thyroid gland, which indicates that the administered 131-I dose may have a diminished radiation effect on the adenomas. In these cats, increased therapeutic 131-I dosages are needed to compensate for the decreased radiation effect to reduce the risk of persistent disease.

Persistent hyperthyroidism—Retreatment plan
If the hyperthyroid state persists in any cat for longer than 3 months after initial treatment, retreatment with radioiodine should be considered. In such cats, thyroid imaging (thyroid scintigraphy) and determination of thyroid uptake may help determine the cause of the initial treatment failure and ensure success with the second 131-I treatment.

In most of these cats, a 131-I dose (higher than that which was originally administered) will be needed to cure their hyperthyroid state. The prognosis remains good, however, and almost all can be cured with the second dose of radioiodine.

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. Peterson ME, Becker DV. Radioiodine treatment of 524 cats with hyperthyroidism. J Am Vet Med Assoc 1995;207:1422-1428.  
6. Slater MR, Komkov A, Robinson LE, et al: Long-term follow up of hyperthyroid cats treated with iodine-131. Vet Radiol Ultrasound 1994;35:204-209.
7. Peterson ME. Radioiodine treatment of hyperthyroidism. Clin Tech Small Anim Pract 2006;21:34-39. 
8. Peterson ME. Diagnostic testing for feline thyroid disease: Hypothyroidism. Compend Contin Educ Vet 2013:in press.
9. Nykamp SG, Dykes NL, Zarfoss MK, et al. Association of the risk of development of hypothyroidism after iodine 131 treatment with the pretreatment pattern of sodium pertechnetate Tc 99m uptake in the thyroid gland in cats with hyperthyroidism: 165 cases (1990-2002). J Am Vet Med Assoc 2005;226:1671-1675.
10. 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.
11. Peterson ME. Treatment of severe, unresponsive, or recurrent hyperthyroidism in cats, in Conference Proceedings 29th Annual Veterinary Medical Forum (American College of Veterinary Internal Medicine) 2011;104-106.
12. Aktay R, Rezai K, Seabold JE, et al. Four- to twenty-four-hour uptake ratio: an index of rapid iodine-131 turnover in hyperthyroidism. J Nucl Med 1996; 37:1815-1819.

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.

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 

How Radioiodine Works to Cure Cats with Hyperthyroidism

Iodine Physiology and the thyroid
Thyroid hormones are the only iodinated organic compounds in the body. Ingested stable iodine (127-I) in the diet 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 the serum (Figure 1). 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 triiodothyronine (T3) (1-3).

Figure 1: Synthesis of thyroid hormones, as seen in an individual cell.
See this link for more information (2).

Radioiodine (131-I): How it works
The radioisotope used to treat hyperthyroidism is radioiodine-131 (131-I). The basic principle behind treatment of hyperthyroidism with 131-I is that thyroid cells do not differentiate between stable (nonradioactive) and radioactive iodine (3-7). Therefore radioiodine, like stable iodine, is concentrated by the thyroid gland after administration (see Figure 1).

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 (4-7).

Unless too large of an I-131 dose is 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 (4-7). In some cats, however, most of the normal thyroid gland has been replaced by tumor. If the I-131 treatment is successful in destroying the thyroid tumor tissue in these cats, they will likely develop hypothyroidism and will require normal thyroid hormone supplementation (4-8). I'll be discussing the issue of iatrogenic hypothyroidism more in my future posts.

Radiation physics and I-131
Radioiodine emits two types of radiation (Figure 2):

• beta (β)-particles
• gamma (γ)-radiation

The β-particles, which cause almost 90% of the tissue damage, travel only a very short distance —a maximum of 2 mm in tissue, with an average path length of 400 μm (3,7,9). Therefore, β-particles are locally destructive to the thyroid tumor but spare adjacent atrophic thyroid tissue, parathyroid glands, and other cervical structures.

Because they contain mass, the β-particles can be thought of as a hail of "bullets," with the cellular DNA of the thyroid tumor as the "target." The higher the I-131 exposure, the more bullets pass near or hit the target to cause the desired tumor destruction (3,7,9).

Gamma radiation, also known as gamma rays and denoted as γ, is a form of electromagnetic radiation (like X-rays). Although gamma rays are a form of ionizing radiation, this plays only a minor role in the destruction of the thyroid tumor following radioiodine treatment (3,7,9).

Figure 2: Radioiodine-131 emits 2 types of radiation — 1) gamma (γ)-radiation as a wave of electromagnetic energy, and  2) β- radiation as a particle.

Radioiodine kinetics in cats with hyperthyroidism
When radioiodine is administered to a cat with hyperthyroidism, between 20% to 60% of the administered dose is taken up and accumulates in the thyroid tumor. The remainder of the administered 131-I is excreted primarily in the urine and to a lesser degree the feces (10,11).

Radioiodine has a physical half-life of 8 days; in other words, the amount of radiation will decrease by half every 8 days (3,7,9). To reach background levels of radiation, we can calculate that I-131 will take approximately 90 days. With regard to our cats, however, we must remember that the biological or effective half-life of I-131 in the cat is much shorter than 8 days because the cats are also excreting the radioiodine into their urine and feces. Therefore, most, if not all, of the measurable radiation will be gone from our cats within 2 to 3 weeks after treatment.

References

1. Miot F, Dupuy C, Dumont JE, et al. Thyroid hormone synthesis and secretion. Thyroid Disease Manager (online), 2012. 
2. Wikipedia. Thyroid hormone. 
3. Wyszomirska A. Iodine-131 for therapy of thyroid diseases. Physical and biological basis. Nucl Med Rev Cent East Eur 2012;15:120-123. 
4. Peterson ME. Radioiodine treatment of hyperthyroidism. Clin Tech Small Anim Pract 2006;21:34-39. 
5. 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.
6. 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.
7. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism. In: Bonagura JD, Twedt DC, eds. Current Veterinary Therapy XIIII. Philadelphia: Saunders Elsevier, 2013: in press.
8. Nykamp SG, Dykes NL, Zarfoss MK, et al. Association of the risk of development of hypothyroidism after iodine 131 treatment with the pretreatment pattern of sodium pertechnetate Tc 99m uptake in the thyroid gland in cats with hyperthyroidism: 165 cases (1990-2002). J Am Vet Med Assoc 2005;226:1671-1675. 
9. Ward WF. Basic principles of radiation biology. In: Henkin RE, Bova D, Dillehay GL et al. Nuclear Medicine. Elsevier, Philadelphia 2006: 507–522.
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. Hays MT, Broome MR, Turrel JM. A multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats. Endocrinology 1988;122:2444-2461.

Treating Hyperthyroid Cats with Radioiodine: The Pros and Cons

Hyperthyroidism is the most common endocrine disorder in cats, most frequently associated with adenomatous hyperplasia (or adenoma) involving one or both thyroid lobes (1,2). 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 for cats with hyperthyroidism
Four treatment options are available for cats with hyperthyroidism (3-8):

• Long-term antithyroid drug administration
• Chronic feeding of an iodine-deficient diet (Hill’s y/d)
• Surgical thyroidectomy
• Administration of radioiodine (131-I) to irradiate and destroy the hyperfunctional thyroid nodule(s)

Each of these treatment options has its advantages and disadvantages, but the use of radioiodine is considered by most authorities to be the treatment of choice for the majority of hyperthyroid cats.

The best treatment option for a hyperthyroid patient is determined by evaluation of age, concurrent medical problems (such as cardiovascular or renal disease), availability of therapy, and the owner’s opinion and financial options (3,5,6,9).

Advantages of radioactive iodine (I-131) as treatment of cats with hyperthyroidism
Radioactive iodine (radioiodine; I-131) provides a simple, effective, and safe treatment for cats with hyperthyroidism.  This form of therapy has many advantages over other treatment methods (4-9).

• Radioiodine avoids inconvenience of daily, oral administration of an antithyroid drug as well as the side effects commonly associated with these drugs. 
• Radioiodine avoids the restrictions associated with the lifelong feeding of an iodine-deficient diet. 
• Radioiodine also eliminates the risks and perioperative complications associated with anesthesia and surgical thyroidectomy.
• A single administration of radioiodine restores euthyroidism in most (>90%) hyperthyroid cats. 
• The therapy is simple and relatively stress-free for most cats. 

Disadvantages of radioactive iodine (I-131) as treatment of cats with hyperthyroidism
Although the therapy is simple and relatively stress-free for cats, there are also a few downsides of radioiodine treatment for some cats.

• The use and treatment with radioiodine requires special radioactive licensing and facilities, nuclear medicine equipment, and extensive compliance with local and state radiation safety laws.
• Major drawback for most owners is that their cat must be kept hospitalized for a period (3 to 10 days in most treatment centers) and visiting is not allowed.
• The cats must be stable enough to undergo this procedure. If severe cardiac or renal disease is present, cats may not do well during this hospitalization period.
• If cats are underdosed with radioiodine, they will remain persistently hyperthyroid and will requrie additional treatment.
• If the cats are overdosed with radioiodine, on the other hand, hypothyroidism may develop (8,10).

Bottom Line

Overall, the use of radioactive iodine provides a simple, effective, and safe treatment for cats with hyperthyroidism. Unlike methimazole or nutritional therapy (iodine deficient diet), use of radioiodine cures the disease. It is regarded by most veterinarians to be the treatment of choice for most cats with hyperthyroidism.

Radioiodine is a particularly useful treatment 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 (8,11,12).

There are different protocols that facilities may use to determine the cats’ radioiodine dosage, which greatly influences the prevalence of persistent hyperthyroidism (when the administered 131-I dose is too low) and iatrogenic hypothyroidism (when the administered 131-I dose is too high). The method of dose calculation should be considered when selecting a radioiodine facility.

References

1. Gerber H, Peter H, Ferguson DC, et al. Etiopathology of feline toxic nodular goiter. Vet Clin North Am Small Anim Pract 1994;24:541-565. 
2. Peterson M. Hyperthyroidism in cats: What's causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 2012;14:804-818. 
3. Panciera DL, Peterson ME, Birchard, SJ: Diseases of the thyroid gland. In: Birchard SJ, Sherding RG (eds): Manual of Small Animal Practice (Third Edition), Philadelphia, Saunders Elsevier, pp 327-342, 2006.  
4. Peterson ME. Radioiodine treatment of hyperthyroidism. Clin Tech Small Anim Pract 2006;21:34-39.
5. 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.
6. Baral R, Peterson ME: Thyroid gland disorders, In: Little, S. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, 2012;571-592.
7. 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.
8. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism. In: Bonagura JD,Twedt DC, eds. Current Veterinary Therapy XIIII. Philadelphia: Saunders Elsevier, 2013: in press.
9. Kintzer PP. Considerations in the treatment of feline hyperthyroidism. Vet Clin North Am Small Anim Pract 1994;4:577–585.
10. Nykamp SG, Dykes NL, Zarfoss MK, et al. Association of the risk of development of hypothyroidism after iodine 131 treatment with the pretreatment pattern of sodium pertechnetate Tc 99m uptake in the thyroid gland in cats with hyperthyroidism: 165 cases (1990-2002). J Am Vet Med Assoc 2005;226:1671-1675.
11. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. J Feline Med Surg 2009;11:116-124. 
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. 

Hyperthyroidism in Cats: Past and Upcoming Topics

As you know, if you have been following this blog, I've spent much of the last few months writing about the diagnosis and treatment of hyperthyroidism, the most common endocrine disorder of the cat.

For my next series of posts, I'm getting back to this series to discuss the next treatment option — namely,  radioactive iodine (radioiodine; I-131), which is considered by most to be the treatment of choice for most cats suffering with hyperthyroidism. I do plan to do a series of posts on a number of issues concerning radioiodine over the next few weeks.

But before I move on to the topics of treatment of this common feline condition, I thought I'd post links to the hyperthyroid topics I've covered thus far:

• Do All Hyperthyroid Cats Have a Thyroid Tumor? Is It Thyroid Cancer? 
• Why Has Hyperthyroidism in Cats Reached Epidemic Levels? 
• Top 10 Signs of Hyperthyroidism in Cats 
• Top 12 Physical Exam Findings in Cats with Hyperthyroidism 
• Hypertension (High Blood Pressure): A Common Problem in Cats 
• 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 Free T3 Concentrations 
• Diagnosis of Hyperthyroidism in Cats: Serum TSH Concentrations 
• Diagnosis of Hyperthyroidism: T3 Suppression Test 
• Diagnosis of Hyperthyroidism: TRH Stimulation Test 
• Diagnosis of Hyperthyroidism: Thyroid Scintigraphy 
• Treatment Options and Considerations for Hyperthyroid Cats 
• Do Hyperthyroid Cats Ever Go Into Spontaneous Remission? 
• Daily Water and Fluid Requirements and Needs for Hyperthyroid Cats 
• Diet and Nutritional Management of Hyperthyroid Cats 
• Treating Cats with Hyperthyroidism: Antithyroid Drugs 
• Antithyroid Drug Treatment for Hyperthyroidism: Brand Name, Generic, or Compounded Drug? 
• How to Dose and Monitor Hyperthyroid Cats on Methimazole 
• Thyroid Tumors Grow Progressively Larger in Most Hyperthyroid Cats Treated with Methimazole 
• Methimazole-Handling Precautions for Cat Owners 
• Alternative Medical Treatments for Hyperthyroid Cats 
• Treating Cats with Hyperthyroidism: Surgical Thyroidectomy 
• Surgical Thyroidectomy in Cats: Thyroid and Parathyroid Anatomy 
• Surgical Thyroidectomy for Cats with Hyperthyroidism: Preoperative Preparation 
• Thyroid Imaging for Preoperative Staging of Hyperthyroid Cats 
• Surgical Thyroidectomy for Cats with Hyperthyroidism: Intraoperative Considerations 
• Thyroidectomy for Cats with Hyperthyroidism: Surgical Procedure 
• Thyroidectomy for Cats with Hyperthyroidism: Surgical Techniques 
• Complications of Thyroidectomy in Cats: Postoperative Hypocalcemia 
• Complications of Thyroidectomy in Cats: Postoperative Hypothyroidism 
• Complications of Thyroidectomy in Cats: Persistent Hyperthyroidism & Relapse 

My next post on feline hyperthyroidism (entitled, Treating Hyperthyroid Cats with Radioiodine: The Pros and Cons) will go up within the next week; then I'll continue with I-131 treatment issues, with a post once a week.