Mode of action of carbimazole in Graves' disease

In a series of hyperthyroid subjects treated with a high dose 'block-replace' regime, mean thyroidal technetium uptake was shown to fall progressively over an 18 month period. Furthermore, sub-total inhibition of hormone biosynthesis could be demonstrated, without evidence of proportionate inhibition of organification, the regression of radio-iodine on technetium thyroid uptake showing similar slopes in euthyroid, treated and untreated hyperthyroid subjects. Together with the reported differential in remission rates between propranolol and anti-thyroid drugs, it is concluded that carbimazole does not act solely by inhibiting intrathyroid hormono-genesis, but more definitively by affecting thyroid hyperstimulation at a pre-biosynthetic level. The inability to demonstrate normal suppressibility of trapping in any subject in the present series despite extended therapy with a 'block-replace' regime, further suggests that current concepts of 'suppressibility' are invalid, the progressive fall in technetium uptake being unlikely to represent spontaneous restoration of a normal pituitary-thyroid axis, but rather a direct influence or prolonged therapy with anti-thyroid drugs on the natural history of the disease.