Is there any relationship between drug treatment with thiamazole (= methimazole) and appearance of

Fråga: Is there any relationship between drug treatment with thiamazole (= methimazole) and appearance of polyneuritis or polyneuralgia?

Sammanfattning: There can be a correlation between methimazole treatment and polyneuritis particularly in long term therapy, since we have found single case reports. The mechanism is not understood.

Svar: METHIMAZOLE - POLYNEURITIS. There are some reports of polyneuritis with methimazole treatment in hyperthyroidism in the literature, but they are few compared to the occurrence of its other side effects (1-4).

We have found single case reports indicating the occurrence of polyneuritis in subjects treated with methimazole. A 50-year-old Hawaiian man developed polyneuritis after methimazole therapy for hyperthyroidism 20 mg daily for 17 days, which was extended later to 30 mg daily for an additional 23 days (1).

Also a 13-year-old girl with Graves´ disease developed peripheral neuritis after 20 months´ of methimazole regimen of 10 mg daily (3,4).

The third case concerns a 67-years-old woman taking carbimazole 40 mg daily and propranolol 60 mg. She developed peripheral polyneuritis after 3 months´ treatment. The women was allergic to penicillin. The authors couldn´t exclude the metabolite (methimazole) to be the reason for the side effect of this last case (5). Methimazole is formed in vivo fram carbimazole which is probably inactive (7).

Another five cases of neuritis related to methimazole treatment were reported by Williams et al (5). Frawley and Koepf reported also a 64 year-old woman with neuropathy after such treatment (quoted in 4).

In all the above case reports the symptoms were reversible with the discontinuation of the drug in different intervals ranging from 2 to 6 months among the patients (1-4).

The mechanism of action and pathology of the process is yet poorly explained. Some authors speculate that variations in pharmacokinetics, might be important for the side effects. Age (case reports were almost all old people), underlying diseases (impaired renal function, diabetes, vitamin deficiency or cancer) and lastly alcolism might also play a role for eliciting the side effects (6). Some authors postulate that the thymine deficiency in hyperthyroid patients may make the nervous system more susceptible to the neurotoxic effect of thiouracil (5). The possible role of peroxidase in nerve function and the anti-peroxidase action of these drugs were also given as a plausible explanation (4), while others argue about immunological involvement of cellular medication (5).

The pathological changes are usually an axonal degeneration with degeneration of the myelin sheath, sometimes there is segmental degeneration (6). 1 Accetta GS, Fitzmorris AO, Wettingfeld RF: Toxicity of methimazole (Tapazole). JAMA 1954; 155: 243-254

2 Meyler/Herxheimer, Side effects of drugs, 1980; 9: 698-699
3 Martindale, Extra pharmacopoeia, 1977; 27: 302
4 Roldan EC, Nigrin G: Peripheral neuritis after methimazole therapy. NYS J Med 1972; 72: 2898-2900

5 Mikol F, Bouchareine A, Fraisse F, Le Pennec PY, Mikol J: Polyradioculonevrite a rechute role possible du carbimazole. Rev Neurol 1979; 135: 835-837 6 Argov Z, Mastaglia FL: Drug-induced peripheral neuropathies. Br Med J 1979; 1: 663-666 7 Melander A, Rosendal-Helgesen S, Sjöberg AK, Wåhlin E: Karbimazol och tiamazol: komparativ dynamik och kinetik hos homo. Riksstämman 1978