Drugs for the Treatment of Hypothyroidism and Hyperthyroidism

T₃ Formulations (Liothyronine)

Liothyronine is the levorotatory isomer of T₃ and is 2.5 to 3.0 times as potent as levothyroxine. Its rapid onset and short duration of action preclude the use of liothyronine for long-term thyroid replacement. T₄-T₃ combination therapy may improve symptoms in a small subgroup of patients with a polymorphism in type 2 deiodinase, which converts T₄ to T₃.⁵

Hyperthyroidism

The treatments for hyperthyroidism are antithyroid drugs, radioiodine, and/or surgery. TSH levels are useful for the diagnosis of hyperthyroidism, but not for determining its degree of severity. Therefore, measuring free T₃ and T₄ is necessary to assess the efficacy of treatment. Once steady state is achieved, TSH can be used to assess the efficacy of therapy.

A large number of substances interfere with the synthesis of thyroid hormones or reduce the amount of thyroid tissue. These compounds include (a) thionamides, (b) inhibitors of the iodide transport mechanism, (c) iodide, and (d) radioactive iodine.

Thionamides (Methimazole, Propylthiouracil, Carbimazole)

Thionamides are antithyroid drugs that inhibit the formation of thyroid hormone by inhibiting thyroid peroxidase to prevent incorporation of iodine into tyrosine residues of thyroglobulin (Fig. 39-2). Thionamides exert immunosuppressive effects via a reduction in concentrations of antithyrotropin-receptor antibodies. In addition to blocking hormone synthesis, propylthiouracil also inhibits the peripheral deiodination of T₄ and T₃.⁶ Antithyroid drugs are useful in the treatment of hyperthyroidism before elective thyroidectomy.

Serum levels of thionamides peak 1 to 2 hours after ingestion.⁶ Thionamides are not available as parenteral preparations. The half-life of methimazole (4 to 6 hours, dosed once daily) is longer than the half-life of propylthiouracil (75 minutes, dosed several times per day). Drug-induced decreases in excessive thyroid activity usually require several days, because preformed hormone must be depleted before symptoms begin to wane. In a few patients, especially those with severe hyperthyroidism, definite improvement is evident in 1 to 2 days.

Side Effects

Minor side effects of thionamide therapy are observed in approximately 5% of patients and include urticarial or macular skin rash, arthralgias, and gastrointestinal discomfort.⁶ Granulocytopenia and agranulocytosis are serious but rare side effects that are most likely to occur in the first 3 months of therapy with an antithyroid drug.⁶

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