Thionamides in the treatment of Graves' disease
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
The thionamides, methimazole, carbimazole, and propylthiouracil (PTU), are effective treatment of patients with Graves' hyperthyroidism. They are actively transported into the thyroid gland where they inhibit both the organification of iodine to tyrosine residues in thyroglobulin and the coupling of iodotyrosines (figure 1) . (See "Pharmacology and toxicity of thionamides".)
The clinical use and efficacy of the thionamides in the treatment of Graves' hyperthyroidism will be reviewed here; the pharmacology and toxicity of these drugs, as well as other treatment options for Graves' hyperthyroidism, are reviewed separately. (See "Pharmacology and toxicity of thionamides" and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment".)
Thionamides are often started in patients with Graves' hyperthyroidism to attain a euthyroid state rapidly in preparation for radioiodine therapy or thyroidectomy. However, patients who want to avoid or defer ablative therapy with radioiodine or surgery can continue the thionamide for prolonged periods. Although hyperthyroidism can almost always be controlled as long as the drug is taken, overall, only approximately 20 to 30 percent of patients achieve a permanent remission. This estimate includes patients with severe disease in whom remissions are unlikely, as well as patients with mild disease in whom remission rates may be as high as 75 percent. (See 'Rate of prolonged remission' below.)
Patients treated with thionamides take three to eight weeks to become euthyroid because they block new hormone synthesis, and any already formed thyroxine (T4) and triiodothyronine (T3) stored in the colloid must be secreted and metabolized for clinical improvement to occur.
Thionamide drugs are contraindicated in patients with a previous major adverse reaction to thionamides (eg, agranulocytosis, hepatotoxicity). (See "Pharmacology and toxicity of thionamides", section on 'Toxicities and their management'.)
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- CLINICAL USE
- INITIATION OF THERAPY
- Choice of drug
- Pretreatment evaluation
- APPROACH TO STOPPING THERAPY
- Duration of therapy
- Evaluation prior to stopping therapy
- Monitoring for recurrence
- Time course of relapse
- Treatment of recurrence
- Rate of prolonged remission
- Predictors of remission
- - Clinical factors
- - Role of thionamide dose
- - Role of combination therapy with T4
- Mechanism of remission
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS