Carbimazole is most often used in the UK, and propylthiouracil is also used. Methimazole, the active metabolite of carbimazole, is used in the USA. These drugs inhibit the formation of thyroid hormones and also have other minor actions; carbimazole/methimazole is also an immunosuppressive agent.
Although thyroid hormone synthesis is reduced very quickly, the long half-life of T 4 (7 days) means that clinical benefit is not apparent for 10-20 days.
As many of the manifestations of hyperthyroidism are mediated via the sympathetic system, beta-blockers may be used to provide rapid partial symptomatic control; they also decrease peripheral conversion of T 4 to T 3.
Drugs preferred are those without intrinsic sympathomimetic activity, e.g. propranolol. They should not be used alone for hyperthyroidism except when the condition is self-limiting, as in subacute thyroiditis.
Subsequent management is either by gradual dose titration or a 'block and replace' regimen. Neither regimen has been shown to be unequivocally superior.
About 50% of patients will relapse after a course of carbimazole or propylthiouracil, mostly within the following 2 years but occasionally much later. Long-term antithyroid therapy is then used or surgery or radiotherapy is considered (see below).
Most patients (90%) with hyperthyroidism have a diffuse goitre but those with large single or multinodular goitres are unlikely to remit after a course of antithyroid drugs. Severe biochemical hyperthyroidism is also less likely to respond.
The major side-effect is agranulocytosis that occurs in approximately 1 in 1000 patients usually within 3 months of treatment.
All patients must be warned to seek immediate medical attention if they develop unexplained fever or sore throat - written information is essential. Rashes are more frequent and usually require a change of drug.
If toxicity occurs on carbimazole, propylthiouracil may be used and vice versa; side-effects are only occasionally repeated on the other drug.