A Hyperthyroid Patient with Graves' Disease Who Was Strongly Resistant to Methimazole: Investigation on Possible Mechanisms of the Resistance.

Abstract

Abstract. We treated a patient who was hyperthyroid due to Graves' disease and strongly resistant to methimazole (MMI): in spite of good compliance, she needed 150 mg of MMI daily to control her hyperthyroidism.To elucidate the reasons of resistance to MMI, her serum and intrathyroidal MMI concentrations were determined by high pressure liquid chromatography (HPLC). After taking a 30 mg dose of MMI, she had a similar serum MMI concentration-time curve to that of a normal subject: drug malabsorption and rapid drug metabolism were not evident when studied after surgical treatment. After her serum containing MMI was incubated with Protein G, the MMI concentration of the fraction not bound to Protein G did not change significantly from that of untreated serum: the possibility of anti-MMI IgG antibody production was considered unlikely. Furthermore, the intrathyroidal concentration of MMI in a surgically obtained tissue specimen was 3 µg/g wet tissue and appeared to be comparable with those of other Graves' tissues reported. Considering that the patient had been taking 150 mg per day of MMI by the time of thyroidectomy, her intrathyroidal MMI concentration was relatively low, suggesting possible impairment of intrathyroidal MMI accumulation.The possibilities of impaired intrathyroidal actions and the severity of hyperthyroidism, especially high T3 levels, also remained as possible causes. In conclusion, here was a severely hyperthyroid patient who was poorly responsive to conventional doses of MMI, and impairment of thyroid uptake of MMI or of pathways after uptake were considered as possible mechanisms.

Resistant Thyrotoxicosis in a Patient with Graves Disease: A Case Report

“…Refractory cases have mostly shown resistance to high-dose thionamides and beta-blockers; rarely resistance to iodine has also been reported [11–13, 15–18]. In our patient, resistance to two different thionamides was seen.…”

“…Possible mechanisms mediating resistance in cases refractory to conventional treatment may range from drug malabsorption, rapid drug metabolism, antidrug antibodies, impairment of intrathyroidal drug accumulation or action, and predominant elevation of T3 rather than T4 levels [15]. …”

Refractory thyrotoxicosis induced by iodinated contrast agents treated with therapeutic plasma exchange. A case report

“…Some cases of hyperthyroidism responding poorly to conventional doses of methyma- zole are described in the literature. An impairment of thyroid uptake of methimazole or of pathways after uptake is considered as possible mechanisms [17]. It is also reported that a high intrathyroidal iodine content due to amiodarone intoxication can reduce the effectiveness of thionamides [18].…”

A Case of Graves' Disease Resistant to Carbimazole

“…(7)There are various reasons for possible resistance to carbimazole. These include malabsorption of the drug, rapid metabolism of the drug, antidrug antibodies and defects in intrathyroidal drug accumulation or action (4).…”