Treatment of Hyperthyroidism 91 zation of the treatment regimen for each patient. Again, it prolongs the time for most patients to become euthyroid, but the results in one such trial appear promising with only 3 percent hypothyroidism at 7 to 16 years following initiation of therapy in 334 patients.*’ High-Dose Radioiodine Followed by Replacement Therapy Since it is felt by some that every patient treated with ''I will eventually become hypothyroid, and since the onset may be very gradual and unnoticed by the patient until the process is advanced, an opposite approach has been taken. Using an initial dose which is rather high (160 to 200 Ci/g) causes rapid reversal of the hyperthyroid state with 90 percent of the patients controlled within 3 months.*® Thyroid replacement therapy was instituted in the controlled patients, to be continued for the remainder of each patient's life. Although this approach appearsto be practical in that it brings the hypothyroid state under rapid control and reduces the possibility of an advanced stage of unrecognized hypothyroidism, it is intellectually not satisfactory. This is especially true at this time when patients under the age of 40 years receive '*"I. In selected patients with cardiac disease and in the older age group this method is certainly a valid one. A continued search for a way to achieve a euthyroid state in each patient with hyperthyroidism is indicated. Use of External Beam Irradiation The hyperthyroid gland is more sensitive than the normal gland to ionizing radiation. Radiation doses which do not affect normal rat thyroid cell function (1000 rads, x-ray, or 5000 rads, !9!I) can have a marked effect on human thyrotoxic thyroid cells.*° External beam therapy wasused in the treatment of hyperthyroidism prior to the availability of antithyroid drugs and radioiodine.‘°** The older literature is difficult to evaluate precisely because of problems with specification of dose and in the diagnosis of thyroid status. However, it is apparent that the success rate in curing hyperthyroidism was good (80 to 90 percent) with doses probably under 2000 rads to the thyroid. Post-therapeutic hypothyroidism appears to have been low, both short term and long term, but the adequacy of follow-up andability to detect developing hypothyroidism are in question. It is of interest, in view of recent theories of the etiology of hyperthyroidism, that Groover et al.*° also irradiated the thymus in addition to the thyroid. On the other hand, much higher doses of radiation delivered to the thyroid in the course of treatment of malignancies in the pharynx and larynx produce only minor suppression of radioiodine uptake without long-term effects. A biphasic suppression is noted at 3 to 4 weeks and again at 3 to 4 months with slightly higher uptakes in the intervening period.4** Einhorn and Wikholm* found only 3 cases of hypothyroidism 10 or more years following high-doseirradiation to 43 patients. However, they did demonstrate diminished reserve as evidenced by lack of re- sponse to TSH stimulation in the clinically euthyroid patients. A morerecent attemptto treat thyrotoxicosis with external beam therapy has been described by Philp et al.*7 Cobalt 60 irradiation in doses of 115 to 900 rads in