MODE OF ACTION OF CARBIMAZOLE IN GRAVES' DISEASE

Abstract

In a series of hyperthyroid subjects treated with a high dose block-replace regime, mean thyroidal Tc uptake fell progressively over an 18 mo. period. Sub-total inhibition of hormone biosynthesis could be demonstrated, without evidence of proportionate inhibition of organification, the regression of radio-iodine on Tc 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, carbimazole does not act solely by inhibiting intrathyroid hormonogenesis, but more definitively by affecting thyroid hyperstimulation at a prebiosynthetic 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 Tc uptake being unlikely to represent spontaneous restoration of a normal pituitary-thyroid axis, but rather a direct influence of prolonged therapy with anti-thyroid drugs on the natural history of the disease.