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).