Current and emerging treatment options for Graves’ hyperthyroidism
Prakash Abraham, Shamasunder Acharya
Treatment of thyrotoxicosis
Andrei Iagaru and I. Ross McDougall
The starting dose of CBZ/MMI is usually between 20 to 40 mg/day depending on the severity of the hyperthyroidism. PTU is started at between 100 to 150 mg 3 times a day with 100 mg of PTU considered equal to about 10 mg of CBZ/MMI. The initial high dose of the drugs can be tapered down after 4 to 8 weeks in what is referred to as the titration regimen. A maintenance dose of 5 to 20 mg of MMI or equivalent is achieved by about 4 to 6 months and this is continued for 12 to 18 months. The block–replace regimen refers to the option of maintaining the high dose of antithyroid drugs while adding levothyroxine to maintain euthyroidism. This has the advantage of fewer thyroid function tests (TFTs) but there is some evidence of a higher frequency of side effects. About 12 trials (Table 1) have examined these regimens. The relapse rates are similar at over 55% but the withdrawal due to side effects (16% versus 9%) and complication rates including rashes and agranulocytosis were higher in the block–replace regimen. One trial that used CBZ 100 mg daily led to 7 out of 17 (46%) withdrawing from the high dose arm due to side effects and 2 cases (12%) had agranulocytosis, a potentially fatal complication.
Radioiodine may be given using fixed high doses or by calculated doses following uptake studies. The risks of radioiodine including eye disease and the role of prophylactic steroid therapy are discussed. The commonly used antithyroid drugs include carbimazole, methimazole and propylthiouracil; however a number of other agents have been tried in special situations or in combination with these drugs. The antithyroid drugs may be given in high (using additional levothyroxine in a block–replace regimen) or low doses (in a titration regimen).
This review examines the current evidence and relative benefits for these options as well as looking at emerging therapies including immunomodulatory treatments such as rituximab which have come into early clinical trials. The use of antithyroid therapies in special situations is also discussed as well as clinical practice issues which may influence the choices.