Issue of interest:
In Graves’ disease, hyperthyroidism results from the action of thyroid stimulating antibodies directed against the thyrotropin receptor on the surface of the thyroid cells. These immunoglobulin G (Ig G antibodies) bind to the surface of thyroid cells and stimulate those cells to overproduce thyroid hormones.
Carbimazole is a thionamide that blocks thyroid hormone synthesis; on the other hand, levothyroxine is the drug of choice for hormone replacement therapy in the treatment of hypothyroidism. What is the rationale of adding levothyroxine to carbimazole in AS?
Carbimazole is given 20-60 mg/day as 2-3 divided doses until patient becomes euthyroid (usually after 4-8 weeks). For maintenance dose, the dosage of carbimazole is gradually reduced to maintain normal thyroid activity. Therapy is usually continued for 12-18 months.
The evidence that high doses of antithyroid drug have an immunosuppressive effect has led to implementation of block-replacement regimen by some clinicians. In this regimen, the dose of carbimazole is maintained at initially high level (20-60 mg/day) and supplemental thyroxine (50-150 mcg/day) is given in order to prevent an underactive thyroid induced by the high carbimazole dosage. (prevention of iatrogenic hypothyroidism). Therapy is usually continued for 12-18 months.
A systematic review of 12 trials that compared a Block-Replace regimen (requiring a higher dose of anti-thyroid drug treatment) with a Titration regimen showed that there was no significant difference between the regimens for relapse of hyperthyroidism (relative risk (RR) = 0.93, 95% confidence interval (CI) 0.84 to 1.03). Participants were more likely to withdraw due to adverse events with a Block-Replace regimen (RR = 1.89, 95% CI 1.25 to 2.85).
In 8 out of the 12 studies, the ant-thyroid drug used was carbimazole, the dose ranged between 30 and 60 mg/day in the Block-Replace arms of all these studies except for one study, where a dose of 100 mg/day was used.
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