 iodide may not be necessary to produce euthyroidism. The patient’s thyroid might accumulate and organify iodide and form iodotyrosines, but be unable to synthesize the iodothyronines. Clinical observations to prove this point are not available.
An RIA for PTU has been developed but has not proven useful in monitoring therapy . Doses of 300 mg PTU produced serum levels of about 7.1 µg/ml, and serum levels of PTU correlated directly with decreases in serum T 3 levels.
It is theoretically possible to give therapeutic doses of methimazole by rectal administration in a saline enema or by suppository if the oral route is unavailable . Propylthiouracil has also been administered in suppositories or in enemas and found to be effective in treating hyperthyroidism. In a recent study PTU tablets were mixed in mineral oil, and then with cocoa butter, and frozen, to produce 1 gm suppositories each containing 400mg PTU. Suppositories given 4 times daily maintained a therapeutic blood level(121a). Jongjaroenprasert et al compared the effectiveness of a 400 mg dose of PTU in 90 ml of water vs. 400 mg of PTU given in polyethylene glycol suppositories. Both methods were effective treatments, but the enema appeared to provide greater bioavailability (121.1).
Long Term Therapeutic Program
After the initial period of high-dose therapy, the amount of drug administered daily is gradually reduced to a level that maintains the patient in a euthyroid condition, as assessed by clinical evaluation and serial observations of serum T4 , FTI, or T3 . These tests should appropriately reflect the metabolic status of the patient. Measurement of TSH level is useful when the FTI falls, to make sure that the patient has not been overtreated, but, as noted previously, TSH may remain suppressed for many weeks after thyrotoxicosis is alleviated. Serum T3 levels can also be monitored and are occasionally still elevated when the T4 level is in the normal range. During the course of treatment, the thyroid gland usually remains the same in size or becomes smaller. If the gland enlarges, the patient has probably become hypothyroid with TSH elevation; this condition should be ascertained by careful clinical and laboratory evaluation. If the patient does become hypothyroid, the dose of antithyroid drug should be reduced.
Decrease in size of the thyroid under therapy is a favorable prognostic sign, and more often than not means that the patient will remain euthyroid after the antithyroid drugs have been discontinued. The dose is gradually reduced as the patient reaches euthyroidism, and often one-half or one-third of the initial dose is sufficient to maintain control. The interval between doses — typically 8-12 hours initially — can be extended, and patients can often be maintained on twice- or once-a-day therapy with methimazole . Alternatively, antithyroid drugs can be maintained at a higher dose, and thyroxine can be added to produce euthyroidism. Occasionally ingestion of large amounts of iodide interferes with antithyroid drug therapy.
Duration of Treatment– The appropriate duration of antithyroid drug therapy is uncertain, but usually it is maintained for one year. Treatment for six months has been effective in some clinics but is not general practice . Longer treatment — such as one to three years — does gradually increase the percentage of responders , but this increase must be balanced against the added inconvenience to the patient [125, 126]. Azizi and coworkers have reported treatment of a group of 26 patients for ten years, during which time no serious problems occurred, and the cost approximated that of RAI therapy(126.1). At least one study suggests that treatment with large doses of antithyroid drugs may increase the remission rate, perhaps because of an immunosuppressive action . Body mass, muscle mass, and bone mineral content gradually recover, although bone mass remains below normal [125.1].
Risedronate treatment has been demonstrated to help restore bone mass in osteopenia/osteoporosis associated with Graves’ disease (125.2).
After the patient has