Celebrate the Seventh Annual World Thyroid Day

It's not just cats and dogs that develop thyroid disease. Approximately 750 million people worldwide are affected by thyroid disorders, and the Seventh Annual World Thyroid Day, being held this weekend, has 5 major goals, say the organizations who support it. These include the American Thyroid Association (ATA), the European Thyroid Association, the Asia Oceania Thyroid Association, and the Latin American Thyroid Society.

The thyroid gland produces hormones that regulate the body's metabolism and influence every cell, tissue, and organ in the body, they point out. Hypothyroidism is characterized by symptoms of fatigue, depression, and forgetfulness, while hyperthyroidism is associated with irritability, nervousness, and muscle weakness.

The aims of World Thyroid Day are the following:

• Increase awareness of thyroid health. 
• Promote understanding of advances made in treating thyroid diseases. 
• Emphasize the prevalence of thyroid diseases. 
• Focus on the urgent need for education and prevention programs.
• Expand awareness of new treatment modalities.

The thyroid gland, butterfly-shaped and located in the middle of the lower neck, produces hormones that influence every cell, tissue and organ in the body. The thyroid hormones regulate the body's metabolism—the rate at which the body produces energy from nutrients and oxygen—and affects critical body functions, such as energy level and heart rate.

The thyroid also plays a critical role during pregnancy, the thyroid societies explain. Consequently, the ATA recommends that pregnant women at high risk for thyroid disease should have their thyroid function tested early in their pregnancy. Another important issue is thyroid cancer, which is rapidly increasing, according to the ATA, which says there were 44,670 new cases of thyroid cancer recorded in 2010 in the United States.

But when thyroid cancer is identified and treated early, "the majority of patients can be completely cured," the American Thyroid Association stresses. The organization also notes that it is important to distinguish thyroid cancer from benign thyroid nodules, which are common in the population.

Patient education on human thyroid conditions can be found on the ATA website at http://www.thyroid.org/patient-thyroid-information/.

How to Manage Hyperthyroid Cats that Become Resistant to Methimazole

I have a 19-year old female DSH cat who was diagnosed with hyperthyroidism 5 years ago. I chose not to do the radioactive treatment because that treatment required her being away for several days. I didn't want to do surgery to remove the thyroid gland because she was very weak at the time of the initial diagnosis. 

Therefore, I have been treating her with methimazole over all these years. Initially, her daily dosage was 5 mg (divided twice daily). Over the years, it has become necessary to increase this first up to 10 mg/day, then to 15 mg (daily doses divided into 2-3 doses per day). This 15-mg dosage was effective at controlling her hyperthyroidism for a short time, but now her serum thyroid value is high again. Because of the persistent hyperthyroidism, many of her clinical signs have returned. She has lost weight, despite the fact that her appetite has increased.  I have just increased the methimazole dose up to 10 mg twice a day (20 mg/day) but this still does not appear to be helping.  Now I am worried about the effects of the medicine on her kidneys.

Do cats just become accustomed to the methimazole and always need an increasing amount?  How high can we go with the dosage of the methimazole?  

Thank you. 

My Response: 

This scenario that you are describing isn't that uncommon in cats treated with methimazole on a long-term basis. All hyperthyroid cats, as you may know, have one or more thyroid adenomas (benign thyroid tumors), which will continue to grow larger with time (1-7).

Thyroid scans of hyperthyroid cats, illustrating that all of these cats will have a thyroid tumor that will continue to grow larger over time. In some cats, these tumors will become very large or huge, which can lead to "resistance" to methimazole.

How methimazole works to control hyperthyroidism
Methimazole and other antithyroid drugs work by being taken up by the thyroid tumor where the drugs inhibit thyroid hormone production and secretion (1-4,7). Therefore, most hyperthyroid cats will require higher dosages of methimazole to inhibit thyroid hormone secretion as their goiters become larger and the thyroid tumor volume increases.

The methimazole does not change the tumor pathology and cannot stop the tumor from growing (5,6).  In some of these cats, the thyroid adenoma also may transform into a thyroid carcinoma as the disease progresses (6,8). Again, methimazole does nothing to the tumor pathology and cannot stop this from happening.

Why methimazole may become ineffective with time
In answer to one of your questions, hyperthyroid cats do not just become accustomed to the methimazole and need an increasing amount. There is a good explanation for the dose increases and why the drug will fail to work in some cats, especially in those treated chronically.

After use of medical treatment for a number of months to years, many hyperthyroid cats will have fairly large palpable goiters (thyroid enlargement). Because of the large goiter size, these cats can be difficult to regulate and make euthyroid, even when very high daily doses of oral or transdermal methimazole are administered (7). The reason for this is simple— with time, we just can't give a dose of methimazole that is high enough to block thyroid secretion from all of the thyroid tumor cells. In other words, the cat just has too much thyroid tumor tissue and thyroid oversecretion can no longer be adequately suppressed by the methimazole.

How high can we go with the methimazole dose in this cat?
So, what do you do?  The dose of methimazole needed to control hyperthyroid cats is based on what it takes to lower the serum T4 concentration into the reference range, so there is not an upper limit to what methimazole dosage can be used. I've gone as high as 30 mg per day in some cats, although the incidence of side effects tends to be higher as you raise the dose (7). So in your cat, I would continue to raise the dose up to 25 mg and then 30 mg/day, as needed. If this fails to completely control the hyperthyroidism, addition of other drugs such as beta-adrenergic blockers (e.g., atenolol) and/or L-carnitine could also be considered (9, 10).

If your cat was younger, I would strongly recommend definitive therapy (i.e., surgery or radioiodine) in order to remove or destroy the thyroid tumor(s). However, at 19-years of age, that may no longer be feasible, depending on your cat's overall clinical condition.

My Bottom Line:
The underlying cause of hyperthyroidism in all affected cats is a hyperfunctional thyroid tumor. Unless surgically removed or irradiated with radioiodine, these thyroid tumors will tend to grow larger with time, as the disease progressed. If methimazole is used as initial treatment, the drug may eventually become ineffective, even when higher dosages of the drug are used.

Overall, I believe that we should be curing the thyroid tumor in the hyperthyroid cat with definitive treatments, not just controlling the hyperthyroid state for the rest of the cat's life with methimazole. In most hyperthyroid cats, especially those that are young to middle-aged, the use of surgical thyroidectomy or radioiodine are, therefore, the treatments of choice. I do not generally recommend using methimazole on a long-term basis, unless we don't believe that the cat will live for another couple of years. Both surgery and radioiodine can be more difficult in cats with large goiters and severe hyperthyroidism, so early definitive therapy is always best.

References:

1. Peterson ME. Hyperthyroid diseases In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Fourth ed. Philadelphia: WB Saunders Co, 1995;1466-1487.
2. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
3. 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.
4. 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.
5. 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.  
6. 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. 
7. Peterson ME. Treatment of severe, unresponsive, or recurrent hyperthyroidism in cats. Proceedings of the 2011 ACVIM Forum; 2011 June 15–19; Denver, CO. American College of Veterinary Internal Medicine, pp 104–106.
8. 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 2012;26:1523.
9. Peterson ME. Alternative medical treatments for hyperthyroid cats. Conference Proceedings North American Veterinary Conference (NAVC) Conference 2012: Small Animal & Exotics Proceedings 2012;852-858.
10. Peterson ME. Alternative Medical Treatments for Hyperthyroid Cats. Animal Endocrine Clinic blog, September 13, 2012.

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

What's the Human Risk Associated with Handling of Thyroid Medications?

Maybe I am missing something here, but I have a question about the human risk associated with handling thyroid medications. Why do you state that owners should be careful when handling and cutting methimazole tablets (Tapazole of Felimazole) because of the human safety concerns (1,2), when I can find no mention that we should use any precautions when handling or cutting L-thyroxine (L-T4) tablets?  I've heard that we should wear gloves when handling methimazole tablets or applying methimazole transdermally to the cat's ear, but no one has ever mentioned the need for gloves with L-T4 tablets.

So why is handling L-thyroxine any less of a concern than handling methimazole? Do they not both have the same potential to affect human thyroid levels? If handling methimazole can lower a human's thyroid levels, why wouldn't handling an L-thyroxine preparation potentially lead to hyperthyroidism?

My Response: 

Methimazole and L-thyroxine are totally different drugs, with different patterns of absorption and metabolism. Methimazole is a potent antithyroid drug whereas L-thyroxine is a synthetic form of natural thyroid hormone.

Methimazole
As you state, we must be careful when cutting methimazole tablets or applying transdermal methimazole since either form of methimazole could potentially be absorbed via human skin (1,2). Methimazole is a human teratogen (i.e., the drug may cause birth defects) and crosses the placenta concentrating in the fetal thyroid gland. Besides being a safety issue in pregnant women or women who may become pregnant, the drug should not be handled by lactating women because methimazole is transferred in breast milk at a high rate.

The same precautions pertain regardless of what methimazole product is used, i.e., the veterinary brand-name Felimazole preparation or a human brand-name or generic product. The methimazole tablets should not be cut with our bare hands. We want to wash our hands after administering the medication to minimize skin and oral contamination; repeated and chronic exposure could pose a risk.

L-Thyroxine
As compared to methimazole, L-thyroxine is not absorbed well from the skin. Results of two studies found that the hormone is not absorbed into the systemic circulation to have an effect on all tissues of the body (3,4). In support of that, of the few dogs that I have evaluated on transdermal L-T4, none have responded to the transdermal replacement therapy with a rise in serum T4 concentrations (5). I know that some compounded pharmacies will sell transdermal preparations of L-T4 but I do not believe that they actually work. Ask for some actual data and you will get none!

So go ahead and cut all the L-T4 pills that you want. It will not get absorbed unless you ingest the hormone supplement so you should still wash your hands to remove any residual L-T4 residue from your hands.

References:

1. Peterson ME. Methimazole-Handling Precautions for Cat Owners. Blog post, Animal Endocrine Clinic, September 2, 2012.
2. Felimazole-Coated Tablets. Product insert. Available at: www.dechra-us.com/files/dechraUSA/downloads/Product%20inserts/Felimazole.pdf 
3. Padula C, Pappani A, Santi P. In vitro permeation of levothyroxine across the skin. Int J Pharm 2008 12;349:161-165. 
4. Padula C, Nicoli S, Santi P. Innovative formulations for the delivery of levothyroxine to the skin. Int J Pharm 2009;372:12-16.
5. Peterson ME. Alternative Dosage Forms of L-Thyroxine for Hypothyroid Dogs. Blog post, Insights into Veterinary Endocrinology, March 28, 2012.

Using a Low-Iodine Diet (y/d) in Hyperthyroid Cats Allowed Outdoors

Is feeding the low-iodine diet (Hill's y/d) an appropriate or reasonable choice for a hyperthyroid cat that is allowed outside and hunts? 

Will the diet work to control the hyperthyroid state if the cat eats small prey?

My Response: 

No, Hill's y/d would not work to lower the high serum T4 and T3 in a cat in this situation.

All species (cattle, pigs, chickens, birds, mice and other rodents) all contain iodine in their muscle tissue (1,2). Iodine may be ingested in the diet as a supplement, but it's also present in soil, which ends up in the plants ruminants and other animals may eat (3,4). Remember that iodine is an essential nutrient and is needed by all animals (including humans!).

This cat, by eating birds and rodents (not eating an iodine deficient diet, of course), would ingest too much iodine for the y/d to be effective. To lower T4 secretion, the diet has to be very, very low in iodine.

References:

1. Hemken RW. Factors that influence the iodine content of milk and meat: a review. Journal of Animal Science 1979;48:981-985.  
2. Downer JV, Hemken RW, Fox JD, et al. Effect of dietary iodine on tissue iodine content in the bovine. Journal of Animal Science 1981;52:413-417. 
3. Whitehead DC. Studies on iodine in British soils. Journal of Soil Science 1973;24:260-270.  
4. Fuge R, Johnson CC. The geochemistry of iodine — a review. Environmental Geochemistry and Health 1986;8:31-54.

Difficult Swallowing in Cats with Hyperthyroidism

We have a 13-year old male cat named Balki with hyperthyroidism and moderate renal disease. He has a history of diabetes, but that has been in remission for the latter for several months.

Balki's main problem at the moment is trouble eating. My veterinarian just puts it down to the renal disease. However, it seems he wants to eat, but has difficulty swallowing. It has progressively gotten worse, to the point where he is now barely eating.

He also has had several episodes of reverse sneezing. When trying to eat, he extends his neck and gulps, then turns away from the food being offered. He also sometimes drools, and often spits out the food. He has most difficulty with dry food.

Can you give any advice on what might be causing this, and what tests he might need to find out, and how to help him to be able to eat?

My Response:

The typical hyperthyroid cat eats well (usually an increased appetite). These cats almost never develop anorexia, and difficulty swallowing (dysphagia) never occurs as a direct result of hyperthyroidism (1-4).

Most cats with moderate to severe renal disease will develop a decreased appetite as a result of their uremia, but they don't show signs of dysphagia (5). Most likely, your cat has disease either in the caudal pharygeal (throat) region or esophagus that is causing some obstruction to the food eaten (6-10). With the history of reverse sneezing, I'd say the problem is most likely in the caudal pharynx.

I'd recommend starting with a good oral examination (under sedation) to look for a lesion or mass in the pharygeal area. If nothing is seen, then endoscopy may be needed. Radiography or other imaging (e.g., CT scan) may also be required to help define the extent of your cat's disease (9-11).

Could thyroid tumors ever grow large enough to compress the esophagus and produce signs of dysphagia? That would be extremely unlikely, since even cats with large thyroid carcinomas almost always continue to eat well and don't have any problems swallowing.  However, I have had two cats in my career that had thyroid carcinoma which invaded the esophagus, leading to signs of esophagitis and esophageal obstruction. In any case, the chance of that being the problem in your cat would be about 1 in a million; again, that would best be diagnosed with endoscopy and CT imaging.

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. Top 10 signs of hyperthyroidism in cats. Animal Endocrine Clinic blog post. March 21, 2011.
5. DiBartola SP, Rutgers HC, Zack PM, et al. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984). J Am Vet Med Assoc 1987;190:1196-1202. 
6. Watrous BJ. Clinical presentation and diagnosis of dysphagia. Vet Clin North Am Small Anim Pract 1983;13:437-459.  
7. Vos JH, van der Gaag I. Canine and feline oral-pharyngeal tumours. Zentralbl Veterinarmed A 1987;34:420-427.
8. Mattson A. Pharyngeal disorders. Vet Clin North Am Small Anim Pract 1994;24:825-854. 
9. Gengler W. Gagging. In: Ettinger SJ, Feldman EC, eds.The Textbook of Veterinary Internal Medicine. St Louis, Mo, USA: Saunders Elsevier; 2010:189–191.  
10. Jergens AE. Diseases of the esophagus. In: Ettinger SJ, Feldman EC, eds. The Textbook of Veterinary Internal Medicine. St Louis, Mo, USA: Saunders Elsevier; 2010:1487–1499. 
11.  Pollard RE. Imaging evaluation of dogs and cats with dysphagia. ISRN Vet Sci 2012;2012:238505. 

Can a Special Diet be Formulated to Treat Hyperthyroidism in Cats?

I have a 13-year old female DSH cat that has recently been diagnosed with hyperthyroidism. Unfortunately found out that she is severely allergic to methimazole (severe vomiting and anorexia), so I cannot treat her with medication (even though I've read this medicine can cause other health issues).

My next option was to feed her the Hill's y/d diet, but she absolutely refuses to eat that food. I then began an online search to see if I could make my own low-sodium cat food that would mimic the Hill's diet. My online research brought me to your blogs about hyperthyroidism and diet.

After reading many of your blogs, I found where you say that a high protein/low carb diet is beneficial to the hyperthyroid cat (http://endocrinevet.blogspot.com/2011/09/best-diet-to-feed-hyperthyroid-cats.html), but it doesn't address sodium content.

Do you believe a diet referenced in your blog would be a life-long treatment for a cat with hyperthyroidism? Or should I pay a veterinary nutritionist to compose a diet for my cat with an iodine level at or below 0.32 ppm (www.2ndchance.info/lowIodine.htm), which Hill's y/d diet allows? I recently called the nutritionists at UC Davis about such a diet, but was told that they have never made a diet for hyperthyroidism in cats.

I've also read that too low of sodium in a cat's diet will cause the thyroid to once again over-produce hormones to compensate. To say the least, I'm confused. I'm at a crossroad wondering if I should try a diet or go ahead and have the I-131 treatment done for my cat. 

Thank you so much for your opinion and response.

My Response:

High protein, low-carbohydrate diet for hyperthyroid cats
First of all, my recommendation to feed hyperthyroid cats a diet higher in protein and lower in carbohydrates is based on what we know about the secondary complications of hyperthyroidism.

Hyperthyroidism is a hypermetabolic, catabolic state. Therefore, in hyperthyroidism, the body may be forced to use it's own muscle tissue to supply increased energy it needs. Because of these increased protein needs of the hyperthyroid cats, loss of lean body mass and muscle wasting is common. By adding more protein to the diet, this will help preserve or restore lost muscle mass, but feeding a high protein diet, by itself, will do nothing to lower thyroid hormone secretion or correct hyperthyroidism.

My recommendation for feeding hyperthyroid cats a low-carb diet is based on the fact that hyperthyroid cats commonly develop a form of prediabetes. Feeding a lower carb diet will help prevent the onset of overt diabetes in these cats. Even if this was not true, cats have absolutely no dietary requirement for carbohydrate and cats in the wild would normally ingest only 1-2% of their daily calories in the form of carbs (1).  But again, limiting the amount of carbohydrates in a hyperthyroid cat's diet would do nothing to treat the hyperthyroid condition.

Overall, a diet higher in protein and lower in carbs, is actually a more "natural" diet for cats (1,2). But this natural diet fed to hyperthyroid cats must be combined with another treatment directed specially at the thyroid gland (e.g., antithyroid drugs, surgical thyroidectomy, or radioiodine).

Salt and the thyroid
In cats, both sodium and chloride (i.e., salt) are required in relatively small amounts in the diet. Nutritional requirements for dietary salt in cats are available from regulation associations or scientific councils, mostly based on studies establishing sodium requirements in cats (3,4). Salt restriction has been historically advocated for cats in some disease states (mainly cardiovascular and kidney diseases) (5,6). No study has confirmed the benefit of such dietary intervention in cats.

However, feeding a cat a low sodium (or salt) diet will not do anything to lower thyroid hormone secretion from the thyroid gland. In other words, we have no evidence at all that a low salt diet can be used as a treatment for hyperthyroidism. Now, because iodine is commonly added to salt as a treatment for iodine deficiency (7,8), using a lower salt diet could lower iodine levels very slightly.

Iodine and the thyroid
The y/d diet made by Hill's (named, Prescription Diet y/d Feline –Thyroid Health) is an iodine deficient diet (9-11). Unlike sodium or chloride, iodine is one of the essential building blocks needed for thyroid hormone synthesis.

The main thyroid hormones secreted by the feline thyroid include thyroxine (T4) and triiodothyronine (T3).  If we look at the thyroxine molecule, it contains four atoms of iodine per molecule, and that's how the common abbreviation "T4" was derived. Triiodothyronine contains one less iodine atom, thus the common abbreviation "T3." Therefore, it's the number of iodine atoms in each of these thyroid hormones that determines the "number" in T4 or T3.

The basis for using a severely restricted iodine diet to treat hyperthyroid cats is that iodine is an essential component of both T4 and T3. With severe dietary iodine deficiency, the thyroid cannot produce adequate amounts of thyroid hormone (8,9).

Hill's y/d is clearly an iodine deficient diet, containing levels of approximately 0.2 mg/kg (0.2 ppm) on a dry matter basis, well below the minimum daily requirement for adult cats (0.46 mg/kg or 0.46 ppm) of food (9-11).  Our current data does indicate that feeding y/d, a diet severely restricted to overtly deficient in iodine, will result in normalization of T4 levels in most hyperthyroid cats. Since iodine is an essential nutrient and has other functions other than making T4 and T3 (12), the long-term effects of such iodine deficiency in cats remains unclear.

Can a low-iodine home-made diet be formulated?

I am well aware of the claim by some, including Dr. Hines, that it is possible to make your own low-iodine diet. However, if this were true, then why would we ever feed the Hill's y/d diet, which is very unnatural? 

You can certainly talk to a veterinary nutritionist about making an iodine-deficient diet for your cat (13). Unfortunately, it is just not that easy to formulate such a diet, and I do not know of anyone who has made one. That's especially true if we want to feed a higher protein, lower-carbohydrate diet (iodine is present is most meat, since iodine is a required nutrient in all animals, including cattle, chickens, and pigs). And remember, cats are meant to eat a low-carb, high-protein diet!

My Bottom Line:

At 13-years of age (a middle-aged senior cat), I would consider a definitive form of treatment of the hyperthyroidism to be ideal. I'd talk to your veterinarian about the possibility of the use of radioiodine or surgical thyroidectomy. Once your cat is cured, then we can concentrate on the use of nutrition to help restore any lost muscle mass and to improve glucose metabolism.

References:

1. Eisert R. Hypercarnivory and the brain: protein requirements of cats reconsidered. J Comp Physiol B 2011;181:1-17.
2. Zoran DL. The carnivore connection to nutrition in cats. Journal of the American Veterinary Medical Association 2002;221:1559-1567.
3. AAFCO (Association of American Feed Control Officials). Official Publication, 2007. 
4. NRC (National Research Council). Minerals. In: Nutrient Requirements of Dogs and Cats. Washington DC, The National Academy Press, 2006:145-192. 
5. Xu H, Laflamme DP, Long GL. Effects of dietary sodium chloride on health parameters in mature cats. J Feline Med Surg 2009;11:435-441. 
6. Reynolds B. Dietary salt and cats: evidence-based approach. Proceedings of the 21st ECVIM-CA Congress, 2011.
7. Zimmermann MB. Iodine deficiency. Endocr Rev 2009;30:376-408. 
8. Zimmermann MB, Andersson M. Assessment of iodine nutrition in populations: past, present, and future. Nutr Rev 2012;70:553-570.  
9. Melendez LM, Yamka RM, Forrester SD, et al. Titration of dietary iodine for reducing serum thyroxine concentrations in newly diagnosed hyperthyroid cats [abstract]. J Vet Intern Med 2011 2011;25:683. 
10. Melendez LM, Yamka RM, Forrester SD, et al. Titration of dietary iodine for maintaining serum thyroxine concentrations in hyperthyroid cats [abstract]. J Vet Intern Med 2011;25:683. 
11. Yu S, Wedekind KJ, Burris PA, et al. Controlled level of dietary iodine normalizes serum total thyroxine in cats with naturally occurring hyperthyroidism [abstract]. J Vet Intern Med 2011;25:683-684. 
12. Patrick L. Iodine: deficiency and therapeutic considerations. Altern Med Rev 2008;13:116-127. 
13. Fascetti AJ, Delaney SJ. Nutritional management of endocrine disease In: Fascetti AJ, Delaney SJ, eds. Applied Veterinary Clinical Nutrition. Chickester, West Sussex: Wiley-Blackwell, 2012;289-300.

Methimazole-induced Overgrooming in Cats

Methimazole-induced facial excoriation in a hyperthyroid cat

I have a 13-year old male DSH cat with hyperthyroidism. He's being treated with methimazole but I can't seem to really get an answer from my vet (or my online searching) as to a side effect I think he is having related to the methimazole treatment. 

Have you seen cats excessively groom and/or fur pull as a side effect of the drug? I've read where that shows up as a side effect of hyperthyroidism, but not the medicine. 

My cat only started doing this (fur pulling mostly) once he was put on 7.5mg/day of methimazole. It's so excessive that three weeks ago, I decided to stop the meds and switch him to Hill's Y/D food. That was a mistake as he lost way too much muscle weight and began to look emaciated. Plus, he had a horrible squeaking noise in his intestines! (I did gradually transition the food over a week, but the GI sounds still persisted).

I now have him back on his normal diet of Orijen Cat food (dry) and Blue Spa Turkey (wet). Anyway, he is 3 days back on the methimazole, eating well and regaining weight. But of course, on the second day of restarting the meds, he started fur pulling again.

I'm at a loss.... wondering if you have run across this ever and have any advice? Thank you so much for your time.

My Response:

This certainly sounds like your cat is having an allergic skin reaction to the methimazole. We don't see this very often in cats or humans treated with methimazole, but drug-induced cutaneous reactions can develop in association with almost any drug in the susceptible patient (1-3).

In cats, we see this most frequently around the head and neck area, and these self-induced excoriations will commonly become quite severe (see photo of cat above) (4). In these cases, we generally are forced to stop the drug and use another form of therapy.

In your cat, the fact that the "fur pulling" resolved after stopping the drug and now has recurred once you have restarted the drug is diagnostic for a cutaneous drug allergy. In this case, it doesn't sound life threatening, but if he were my cat, I would treat him with either radioiodine or surgery and get him off this drug —the pruritis must be making him very uncomfortable.

References: 

1. Svensson CK, Cowen EW, Gaspari AA. Cutaneous drug reactions. Pharmacological Reviews 2001;53:357-379. 
2. Khan DA. Cutaneous drug reactions. Journal of Allergy and Clinical Immunology 2012;130:1225-1225 e1226.  
3. Otsuka F, Noh JY, Chino T, et al. Hepatotoxicity and cutaneous reactions after antithyroid drug administration. Clinical Endocrinology 2012;77:310-315. 
4. Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 1988;2:150-157. 

Is a High Serum T4 or Free T4 Level Always Diagnostic for Hyperthyroidism in Cats?

Thyroid scan (scintigraphy) in a cat suspected of hyperthyroidism. Both thyroid lobes are of normal size and shape. Uptake of the radionuclide by the thyroid is also normal, with a thyroid/salivary ratio of 0.8 (normal <1.5). This is a normal study and rules out hyperthyroidism.
Scintiscan provided by Dr. Michael Broome, Advanced Veterinary Medical Imaging 

I've read on your blog "we almost never see false-positive results with the total T4 test." Since you say "almost," I'm wondering what, if anything, might cause a false-positive result? 

I have a 16-year old, male domestic long hair cat who currently has a total T4 value of 6.0 µg/dl (reference range, 0.8-4.0 µg/dl) after being off of methimazole for 5 weeks. He has a long history of chronic diarrhea associated with inflammatory bowel disease (IBD). 

About a year ago, we suspected hyperthyroidism based on a high-normal total T4 with a high free T4 concentration. He had thyroid scintigraphy at that time to confirm hyperthyroidism and help with his radioiodine dose calculation (we wanted to ensure that he wasn't overdosed — I don't want to end up with a hypothyroid cat!). Surprisingly, the results of this thyroid scintigraphy were negative (see his thyroid scintiscan above), though he was getting iodine supplements at the time. 

About 6 months ago, his serum T4 was a bit higher (and his free T4 remained high) so we started treatment with methimazole. He was on methimazole for about 6 months, which did lower his T4, but the drug seemed to significantly worsen his chronic diarrhea, and he didn't gain any weight.  My veterinarian has never been able to palpate an enlarged thyroid tumor in my cat.

I am interested in I-131 treatment, but would like to be as certain as possible he is hyperthyroid before making arrangements. Could there be any other explanation for high total and free T4 concentrations Do you see false-positive results?

His primary veterinarian and his internist both say they know of no other explanation for high total T4 concentration other than hyperthyroidism. But when I read "almost never" on your blog, that seems to imply it's possible (though unlikely) to get a false-positive test result.  Since I know that you are the expert on feline hyperthyroidism, I thought I would try asking for your advice. I don't want to pursue radioiodine treatment if he isn't truly hyperthyroid. 

My Response:

In older cats that develop clinical signs of hyperthyroidism, confirming a diagnosis of thyroid disease is usually straightforward (1-3). However, the potential for false-negative and false-positive results exists with all thyroid function tests (4,5) — especially in the context of routine screening of asymptomatic cats or cats sick with nonthyroidal disease (such as the IBD in your cat). This can lead to clinical dilemmas and misdiagnosis.

To avoid unnecessary treatment and potentially adverse effects in a euthyroid cat (i.e., normal thyroid status), thyroid function test results must always be interpreted in the light of the cat’s history, clinical signs, and other laboratory findings.

Palpating the thyroid nodule 
All cats with hyperthyroidism have a thyroid nodule (goiter) affecting one or both thyroid lobes, since in all cases there is underlying thyroid pathology leading to the disease (e.g., thyroid adenomatous hyperplasia, adenoma or carcinoma) (6).

Because all hyperthyroid cats must have at least one (if not two and sometimes more) thyroid nodules in order to develop the disease, the finding of a thyroid nodule, either by cervical palpation or by imaging (e.g., thyroid scintigraphy – see later), plays a crucial role in diagnosis in these cats (1-5).

If the veterinarian cannot palpate a thyroid nodule in the cat suspected of having hyperthyroidism, diagnosis becomes much more difficult to confirm, especially in cats with mild or borderline disease or in cats with concurrent illness.

Measuring the total T4 concentration 
A high circulating total T4 concentration is the biochemical hallmark of hyperthyroidism and is extremely specific for its diagnosis (1–5).

False-positive results (i.e., a high T4 in a cat without hyperthyroidism) are relatively rare but are being seen with increasing frequency, especially with the automated T4 immunoassays and in-house testing kits. In agreement with that statement, we recently reported that 1–2% of all cats diagnosed as hyperthyroid based on the finding of a high serum T4 concentration turn out to be euthyroid based on results of thyroid scintigraphy (4,5).

Therefore, if a high serum T4 value is found in a cat that lacks clinical signs of hyperthyroidism, especially if no thyroid nodule is palpated or when concurrent disease is present, one should never hesitate to repeat the serum T4 test using a different technique. In these cases, T4 measured by radioimmunoassay (RIA) or chemiluminescence (Immulite) is preferred (4,5). Alternatively, additional thyroid function testing (complete thyroid profile, thyroid scintigraphy) may also be recommended (4,5,7-10).

Measuring the free T4 concentration 
Many veterinarians believe that determination of a serum free T4 concentration is more reliable than measuring total T4 alone, since free T4 values are more consistently elevated in hyperthyroid cats than are total T4 concentrations (3,11). Although free T4 is a more sensitive diagnostic test than total T4 for diagnosing hyperthyroidism, the test specificity for free T4 is poor, with up to 20% of sick (and some clinically normal) euthyroid cats having false-positive free T4 results (3,11-13).

Caution is, therefore, advised in using serum measurements of free T4 as the sole diagnostic test for hyperthyroidism. As always, it is important to combine these thyroid test results with the cat’s clinical features and the presence of a palpable thyroid nodule to make the correct diagnosis.

More important, however, is the situation in cats that maintain reference interval serum T4 values and are diagnosed as hyperthyroid on the basis of a high serum free T4 concentration. Up to 30% of these cats presenting with a mid- to high–normal total T4 value, together with high free T4 concentrations by dialysis, will turn out to be euthyroid based on results of thyroid scintigraphy (4,13).

It is unclear how much additional useful information is truly gained by the use of free T4 assays over the use of total T4 estimations alone. Many veterinarians mistakenly believe that the finding of high free T4 in a cat is completely diagnostic for hyperthyroidism, especially when total T4 is within the middle to upper half of the reference interval. However, since up to a third of these cats may turn out to be euthyroid (4,13), it is clear that the free T4 test can never be considered a "gold standard" diagnostic test for thyroid disease in cats.

Use of free T4 testing can lead to more confusion than clarity in some hyperthyroid cats; certainly, reliance on free T4 results risks misdiagnosis of hyperthyroidism in many euthyroid cats, especially those with non- thyroidal illness.

Careful monitoring may be best diagnostic approach
So what is the next step if we find a high serum T4 in an asymptomatic cat in which no goiter is palpable? The first steps should always be to repeat the cervical palpation looking for a thyroid nodule and to verify the high T4 concentration. Again, the veterinarian should never hesitate to repeat the serum T4 test using a different technique, with RIA or CEIA preferred in such cats. Again, if we have any doubt about the diagnosis, thyroid scintigraphy should be considered (1,2,4,5).

In many of these asymptomatic cats in which the diagnosis is unclear (e.g., borderline or only slightly high T4 concentration, no obvious thyroid nodule), the best approach is to use close observation rather than start any treatment (4,5). With this cautious approach, one should recheck the cat at 2- to 3-month intervals, and at each visit monitoring the cat’s body weight, carefully re-palpating for a thyroid nodule, and repeating the serum T4 concentration doing a complete serum thyroid panel (T4, free T4, T3 and TSH) (4,5). If the cat is truly hyperthyroid, the thyroid tumor will continue to grow, the serum T4 will eventually rise into the hyperthyroid range, and the cat will lose weight.

My Bottom Line: 

But what's up with your cat? Is he really hyperthyroid? Well, the finding of a T4 value of 6.0 µg/dl is certainly consistent with hyperthyroidism, but I'm bothered by a number of issues with the case.

First of all, his thyroid scan done a year ago was completely normal. Of course, a thyroid tumor could have developed during this period, but the clinical signs a year ago appear to be similar to those your cat is showing at this time.

Secondly, medical treatment made the diarrhea worse, not better. If hyperthyroidism was responsible for your cat's gastrointestinal signs (the main problem), lowering the serum thyroid values should have helped, not made the situation worse.

Thirdly, remember that all cats (as well as all humans) likely have their own individual "reference range," so it's possible that a T4 value slightly outside of the lab's reference range could actually be normal for that individual (14,15). Could it be that your cat normally runs higher thyroid hormone levels than most other cats? Or is current high T4 simply a laboratory error?  That would certainly be the most common reason for the finding of a single "high" T4 concentration in a euthyroid cat.

Finally, you have seen a number of veterinarians (your regular veterinarian as well as internal medicine specialists). Despite multiple exams being performed by different vets, no one has been able to palpate a thyroid nodule.  If this was my cat, I would not rush into treatment without repeating the thyroid scan to document the presence of a hyperfunctioning thyroid tumor.

References:

1. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;92-110. 
2. Baral RM, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;571-592. 
3. 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. 
4. Peterson ME. Diagnostic testing for hyperthyroidism in cats: more than just T4. J Fel Med Surg 2013;15:765-777. 
5. Peterson ME. Diagnostic testing for feline thyroid disease: Hyperthyroidism. Compend Contin Educ Vet 2013:in press.
6. 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. 
7. Mooney CT, Thoday JL, Nicoll JJ, et al. Qualitative and quantitative thyroid imaging in feline hyperthyroidism using technetium-99m as pertechnetate.Vet Radiol Ultrasound 1992;33:313-320. 
8. Daniel GB, Sharp DS, Nieckarz JA, et al. Quantitative thyroid scintigraphy as a predictor of serum thyroxin concentration in normal and hyperthyroid cats.Vet Radiol Ultrasound 2002;43:374-382. 
9. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clin Tech Small Anim Pract 2006;21:10-16. 
10. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. J Vet Intern Med 2012;26:754.
11. 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.
12. Wakeling J, Moore K, Elliott J, et al. Diagnosis of hyperthyroidism in cats with mild chronic kidney disease. J Small Anim Pract 2008;49:287-294. 
13. Peterson ME, Broome MR, Robertson JE. Accuracy of serum free thyroxine concentrations determined by a new veterinary chemiluminscent immunoassay in euthyroid and hyperthyroid cats. Proceedings of the 21st Annual European College of Veterinary Internal Medicine (ECVIM-CA) Congress; 2011.
14. Andersen S, Bruun NH, Pedersen KM, et al. Biologic variation is important for interpretation of thyroid function tests. Thyroid 2003;13:1069-1078. 
15. Andersen S, Pedersen KM, Bruun NH, et al. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab 2002;87:1068-1072. 

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.