When to Stop Methimazole Before Radioiodine Treatment

A client of ours has opted to have her cat's hyperthyroid disease treated by Radiocat. In their pre-treatment instructions they state that the cat must be off methimazole for 2 weeks prior to I-131 treatment. But then the client called another treatment facility, and they told her that the cat can stay on the methimazole right up until the treatment.

So my questions are the following:

1. Which is the right thing to do? Should we stop methimazole or not before the cat is admitted for radioiodine treatment?
2. Will methimazole interfere with the radioiodine treatment? 
3. What is the danger in stopping (or not discontinuing) the methimazole  What problems might develop? Can we protect the cat from those problems and if so, how?

Finally, I would like to get your opinion about the use of "fixed" versus "individualized" radioiodine doses for hyperthyroid cats.  I know that most facilities use a fixed dose (eg, 4 mCi), regardless of size of cat or how elevated the serum thyroid hormone values are in the cats.

My Response:

Should methimazole be stopped before radiodiodine treatment?
Methimazole treatment does NOT appear to interfere with the efficacy of I-131 treatment (1,2), so some facilities say that it's fine to continue the drug up to the day of treatment.

However, think about what we are doing in a hyperthyroid cat to the hypothalamic-pituitary-thyroid axis when we give methimazole (or y/d for that matter). Prior to treatment, all clinically hyperthyroid cats will have undetectable serum TSH levels (3-6)— the high circulating T4 and T3 feed back to the pituitary and shut off TSH secretion. Without any TSH, the "normal" thyroid tissue cannot continue to function and will atrophy. The thyroid tumor doesn't need TSH, and that's why the cat is hyperthyroid.

Untreated hyperthyroid cats generally have undetectable serum TSH concentrations.
Lowering the high serum T4 with methimazole may allow TSH secretion to return to normal. 

Now we give methimazole or y/d. By lowering the serum T4, we lose the negative feedback effect on the pituitary thyrotrophs and tell the pituitary to start secreting TSH once again (4,6,7). This will stimulate the normal, atrophied thyroid tissue to start to function again (8). Part of normal thyroid function is the ability to "take up" iodine from the circulation to make thyroid hormone.

So if we treat a hyperthyroid cat with I-131 that is currently well-controlled on methimazole or y/d, we take the risk that the thyroid iodine uptake in the "normal" tissue would be much greater than it would have been prior to the methimazole administration (2,8). In other words, treating with methimazole may allow more of the radioiodine to get taken up by any remaining normal thyroid tissue and would therefore increase the risk of iatrogenic hypothyroidism (2).

If we stop the methimazole for a few days, we can predict that the high T4 would again shut off TSH and decrease the percentage of I-131 uptake by any remaining "normal" thyroid tissue. That is the reason I like to stop the methimazole for 5-7 days prior to treatment.

In some cats with chronic, severe hyperthyroidism, however, the risk of "thyroid storm" outweighs the rise of iatrogenic hypothyroidism (9). In those cats, I generally continue the methimazole up to the day of treatment. In these select, unstable cases (most of which have been on methimazole for years), I don't want to risk having these cats develop a fatal arrhythmia or cardiac failure because we stopped the methimazole.

Which is better— Fixed I-131 doses or individual I-131 dose calculations?
Giving a fixed dose of 4 mCi of radioiodine to all hyperthyroid cats makes no sense to me, since over half of my cats respond completely to a dose less than 3 mCi, whereas other cats with very large benign goiters need doses of 10-12 mCi.  When I show a series of thyroid scintigraphic images (see Figure below) to cat owners and ask them if it is reasonable that the cats with smaller tumors would need much smaller I-131 doses then the cats with large to huge tumors, they universally agree!

Thyroid scintiscans from 4 hyperthyroid cats, with thyroid tumors ranging from small to very large in size. Obviously, cats with small to medium-sized thyroid adenomas require much lower I-131 doses to ablate their thyroid tumors than do the cats with the much large tumor volumes.

It certainly is much more difficult and requires more work to do individual I-131 dose calculations (thyroid uptakes and thyroid scintigraphy are needed) for hyperthyroid cats (2,10). Obviously, it is much easier for a radioiodine treatment facility to give a standard, fixed dose to all cats. I just don't believe it's better for the cats — those with severe hyperthyroidism can be undertreated, whereas cats with mild hyperthyroidism will be overtreated and are much more likely to develop hypothyroidism.  

References:

1. Nieckarz JA, Daniel GB. The effect of methimazole on thyroid uptake of pertechnetate and radioiodine in normal cats. Vet Radiol Ultrasound 2001;42:448-457. 
2. Peterson ME, Broome MR. Radioiodine for hyperthyroidism. In: Bonagura JD, Twedt DC (eds): Current Veterinary Therapy V. Philadelphia, Saunders Elsevier, 2012; in press
3. Wakeling J, Smith K, Scase T, et al. Subclinical hyperthyroidism in cats: a spontaneous model of subclinical toxic nodular goiter in humans? Thyroid 2007;17:1201-1209. 
4. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34. 
5. Wakeling J, Elliott J, Syme H. Evaluation of predictors for the diagnosis of hyperthyroidism in cats. J Vet Intern Med 2011;25:1057-1065. 
6. Baral R, Peterson ME: Thyroid gland disorders, In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders. pp. 571-592, 2012
7. 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. 
8. Fischetti AJ, Drost WT, DiBartola SP, et al. Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats. Vet Radiol Ultrasound 2005;46:267-272. 
9. Ward CR. Feline thyroid storm. Vet Clin North Am Small Anim Pract 2007;37:745-54.
10. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. J Vet Intern Med 2012; 26:754.