Tuesday, December 24, 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.

  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).


Dale said...

Can Denamarin cause increase in T4 level?

Honeycat just turned 15 in March, and is still playful and eating (100% wet food at this point). She was diagnosed with hyperthyroidism December 2009 with a T4 level of 6.3. She's been pretty well controlled (T4 1.3 to 2.9) with 2.5 mg methimazole bid, however, her liver enzymes were elevated on the blood work done in February 2014. She was put on denamarin for several months, then new blood work revealed still a higher ALT, as well as, a significant T4 increase. Could the denamarin have interfered with the absorption of the methimazole? We discontinued the denamarin and did a recheck 5 weeks later, 8/18, and found not only liver enzymes significantly higher, but, also her T4 was now 14. Her levels were as follows:

date 2/2, 3/25, 7/12, 8/18,
T4 2.9, 1.3, 6.6, 14
ALT 277, 468, 763, 890
ALP 139, 165, 113, 217
She had an ultrasound of her liver that showed normal results. Blood work showed kidney and CBC values normal. We did a bile acid test which did reveal the liver is malfunctioning. My veterinarian and I discussed the possible causes of the elevated liver enzymes could be toxicity caused by the methimazole, or lymphoma (but didn't think so due to CBC being ok). We also discussed the I-131 and surgery treatments for the hyperthyroidism.
I am considering the I-131, however, I'm not sure the thyroid scan is part of the protocol that's done at my veterinarians office. And, after reading about it on your web site, I really feel that's important if we went that route. I am also concerned about her age and the stress of being in the hospital for 5 days. A biopsy of the liver was mentioned to determine the exact cause of liver malfunction, but, I'm not sure if we should just try and resolve the hyperthyroidism first, and see where the liver values go. I think it's alot to have her go through a biopsy and the I-131 procedure.
My dilemma is not knowing what direction I should take. I am going away on September 2 through the 10th and am very concerned she's going to go down hill fast given how elevated the numbers became in just 5 weeks. We're not sure if it's a good idea to increase the medicine in case it's the reason the liver is failing. She lost 2 lbs between March and July, but, she managed to maintain her weight of 8 lbs from July to August. Do you have any advice on what I could do for her for the short term?
Thank you so much for your time you put into this blog and helping pet owners. Dale M

Dr. Mark E. Peterson said...

No, denamarin does not cause the T4 to increase.

In general, cats with liver disease act ill - they tend to have a poor appetite, vomiting, etc. So if your cat is acting normally, then it is more likely that this is a methimazole reaction or it may just be due to the hyperthyroidism. So if your cat is acting well, I would treat with radioiodine first to get the thyroid normalized. If the liver tests remain elevated after that time, then I'd do a liver biopsy.

Dale said...

Dear Dr. Peterson,

Thank you very much for your feedback. I will look into the local hospitals to see what their protocol is for I-131, but, am very interested in contacting your office to possibly pursue bringing HoneyCat to you. Your expertise and quality of care far out way the challenges of getting her there, about 3 1/2 hours away.

While she is still playful, she is looking thin, and has lost muscle mass in her hind quarters. she urinates frequently which is causing slight dehydration. Unfortunately, I cannot do anything for a couple of weeks. I have to be away for 9 days. Should I be considering weaning her off of the medicine while I'm gone? Does she have to be off the methimazole at time of treatment and, if so, how long? I am concerned about her T4 being so high (14). Will she be ok until I can get her treated?

Once again, I am ever so grateful for your opinion and compassion.

Dr. Mark E. Peterson said...

Please call Carol in my office on Monday or Tuesday to get more information (914-864-1631). In general, we like the cats off methimazole for at least a week, but it's not doing any good in your cat anyway. You might want to talk to your vet about using a beta-blocker (Atenolol) instead to help protect the heart.