Your Thyroid: What You Need to Know

I came across this information sheet about "Your Thyroid," which came from the Hormone Health Network.  Although very simplistic, this still makes it clear that the thyroid gland and it's thyroid hormone secretion is very important for overall body function.  It also helps clarify the regulatory feedback system between the pituitary gland (secreting TSH) and the thyroid gland (secreting T4 and T3).  

For more information and fact sheets about specific thyroid diseases, click here. To learn more about other endocrine glands and their diseases, visit the Hormone Health Network website at http://www.hormone.org.

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.

A Tribute to a Special Patient, "The Colonel"

The Colonel after his radioiodine treatment

The Colonel was one of our favorite hyperthyroid patients at the Animal Endocrine Clinic. We first met him over two years ago, when he was referred to us for severe and uncontrolled hyperthyroidism.
His thyroid tumor was huge and resistant to treatment, necessitating a large dose of radioiodine to cure him. 

The Colonel ended up staying with us for a long time after treatment since the owner has small children in the house, but none of us minded; we all loved having this wonderful cat at our practice! He had a super personality and enjoyed each day with a zest for life.  

He later when on to develop hypothyroidism, which we successfully managed with daily thyroid hormone replacement therapy. Unfortunately, he later went on to develop cancer of he urinary bladder, which lead to urinary obstruction and worsening of his kidney failure.

The Colonel's owner wrote this tribute in memory of him. This cat poem puts into words, so beautifully, what we all feel when we lose one of our best friends.  I wanted to share it with all of you so you can get a sense of how special this cat really was to all of us. 

However, I must warn you — you will likely cry as you read this touching epitaph, as we do everytime we reread it. 

We all loved this cat.  He truly will be missed.

Dr. Mark Peterson and Staff at the Animal Endocrine Clinic

Watching the gerbils during his long boarding period at the hospital

GONE 

by Beverly Cole 

I don't have to close the bedroom doors, no longer worried your nails will wreak havoc on the rugs.

I am cleaning up the last kernel of your Lord forsaken litter, a battle that I waged for years, that I have finally won. A pyrrhic victory.

I am picking off fur from my sweater without my usual grumbling. The fur will appear less and less now, the couch clean, no tufts of orange and white randomly floating through the air.

There's no more food to order for you. No more subcutaneous fluids to stave off kidney failure. No more thyroid medication. No heartburn relief pills.

We fought for you as hard as you fought for yourself. No, you fought even harder. You loved your life with a passion experienced by few, as simple and serene as it was.

I am taking your fleece blanket out of the dryer. Your urine stains now replaced by my salty tears.

You were just a cat. A 4-year-old flunky mouser who wound up at a shelter. At your best—16 pounds of pomp and circumstance and brilliance and at your worst — a shrunken shell of what was, desperately clinging to life despite the pain.

I haven't told the kids yet, just saying you're at the doctor when they asked me where you are. The little one calls to you in her small voice, then says "maybe he's in his room and you forgot," she says. No, dearest, I haven't forgotten where he is. When I close my eyes, I see you on the cold steel table, now lifeless, yet still filled with your impenetrable dignity although your eyes are now sunken and still.

I am packing up your brush, the same brush we bought when we started together, 13 years ago. When I groomed you the first time, you meowed and yawned at the same time, rolling onto your back, bored and happy, then gently nipped my hand to remind me who was in charge, a devilish glint in your eyes. When I brushed you this last time, you barely moved your head, so I stopped, not wanting to cause you more pain.

Your fur wasn't always urine soaked. Your smell wasn't always unbearable. That was only recently, after the cancer in your bladder had obstructed your ability to urinate, after the kidney failure had taken over. Before that you were impeccable. Meticulously grooming until your fur shone.

I still hear your cry—strong and plaintive, demanding, not the crusty, faltering mew you have been able to muster recently.

It is hard to be in this house without you. My stomach feels void when I realize that the small crackle I hear is not your footsteps coming upstairs to say goodnight to the kids. I stop myself when I enter the house, almost hearing my voice greet you hello, as I have for the last 13 years. You're not here to answer or come over. You'll never be here again.

I see a ghost of you on the couch waiting for me to sit down at night. I am trying to decide what's more devastating—reliving your death every moment I re-realize you're not here, or knowing that I will get used to your absence.

You were just a cat. You were mine. And I miss you so. My dear, dear friend.

You were my best friend, many times my sole ally, and you trusted me with your life. I hope it was a good one.

The Colonel (1997-2013)

Can Methimazole Cause Anemia in Hyperthyroid Cats?

I am very concerned about my 14-year old male DSH cat. He was diagnosed in the spring with hyperthyroidism and has been treated with oral methimazole (Tapazole). 

 After the first 6 months of treatment, I brought him back to my vet because I was concerned about how skinny he was (very little weight gain on the medication). The vet tested him and increased the Tapazole dosage. He said not to be concerned unless he continued to lose weight.

Now, 2 months later, my cat's weight has held steady on the increased dose of methimazole, but he still remained so skinny that I brought him back for another recheck— even though he wasn't losing weight. It turned out he has developed anemia, so severe that he needed a blood transfusion. He had a bone marrow biopsy, which was consistent with a regenerative anemia. Now my vet wants to just wait and redo his CBC to see how he is in another week.

Because we aren't sure if the methimazole caused the anemia, he isn't putting him back on it right now. He recommended trying Hill's y/d. I tried it (just one can), but my cat isn't keen on it (won't eat it), and he is skinnier than ever now so I don't have the luxury of giving it a chance — I don't want to risk him starving to death!

Now that he's been off the methimazole for about a month. I am really worried about him because he's lost even more weight.

My questions include the following:

1. Can a cat with anemia or recovering from anemia still be a candidate for radioiodine treatment?
2. Can a severely underweight cat be treated for radioiodine treatment? He's only 5 pounds now!
3. If my cat has been off of the methimazole for a month, how much time do we have to get him treated again for his hyperthyroidism? Do we need to restart the methimazole before we do the radioiodine treatment? I'm worried he'll die before I can get it properly addressed. 
4. If I do go for the radioiodine treatment, will he have to wait for a period of time to be treated, since he's eaten a bit of y/d?

Thank you so much!

My Response:

Sorry to hear that your cat isn't doing well. Although rare, antithyroid drugs, including methimazole, can produce hematologic abnormalities, including hemolytic anemia in cats (1-5).  If the drug is responsible for the anemia in your cat, it should never be restarted because that would be life-threatening.

Even if we forget about the anemia for a moment, it is certainly clear that methimazole has not been an effective treatment in your cat. Feeding a low-iodine diet (y/d) might help if he would eat it (many cats won't) but that too is less likely to be successful in cats with severe, chronic, or advanced hyperthyroidism.

Treatment with radioiodine would probably the best treatment, but we would need to be certain that the anemia is resolving before moving forward with this treatment. Anemia is a sign, not a diagnosis in itself. If the methimazole isn't causing it, we need to figure out what is responsible, since that is a sign of serious disease. The good news is that if it is regenerative, that suggests that the bone marrow will be able to respond once the insulting factor (e.g., methimazole) has been removed. Nonregenerative, aplastic anemia is a rare but very serious complication of methimazole treatment in man (5,6), which has only been reported in 1 cat (7); let's hope that this is not the case in your cat.

If the anemia resolves and doesn't recur now that your cat is off the methimazole, I would strongly consider the radioiodine treatment. To do that treatment, we do NOT need to pretreat a cat with methimazole; in fact, we like to have owners stop the drug 1-2 weeks prior to I-131 treatment. Feeding a small amount of y/d will not interfere with the treatment. And finally, severely underweight cats with hyperthyroidism certainly can be treated with radioiodine. Since it's likely that your cat's thyroid tumor may be larger than the average hyperthyroid cat, a larger dose of radioiodine might be needed.

References:

1. Peterson ME, Hurvitz AI, Leib MS, et al. Propylthiouracil-associated hemolytic anemia, thrombocytopenia, and antinuclear antibodies in cats with hyperthyroidism. J Am Vet Med Assoc 1984;184:806-808. 
2. Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. J Vet Intern Med 1988;2:150-157. 
3. Baral R, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. Philadelphia: Elsevier Saunders, 2012;571-592.
4. 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.
5. Yamamoto A, Katayama Y, Tomiyama K, et al. Methimazole-induced aplastic anemia caused by hypocellular bone marrow with plasmacytosis. Thyroid 2004;14:231-235. 
6. Edell SL, Bartuska DG. Aplastic anemia secondary to methimazole-case report and review of hematologic side effects. J Am Med Womens Assoc 1975;30:412-413. 
7. Weiss DJ. Aplastic anemia in cats - clinicopathological features and associated disease conditions 1996-2004. J Feline Med Surg 2006;8:203-206. 
8. 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 (in press).

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. 

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. 

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.