Goiters with High Radioiodine Uptake and Other Characteristics of Iodine Deficiency in Rats Chronically Treated with Aminoglutethimide1,2

In experiments with rats, small doses of the antithyroid drug aminoglutethimide (AG), given as a single injection (2 mg) or as an admixture to an iodine-enriched diet for a few days, had a propylthiouracil-like action on thyroidal radioiodine metabolism characterized by a decrease of uptake, organic binding, release of labeled PBI and synthesis of iodothyronines. However, chronic administration of AG for more than 3 weeks produced small goiters characterized by an increase of radioiodine uptake and organic binding and an accelerated release of labeled PBI, while iodothyronine synthesis returned to control levels. With labeling times of 4 hr or less, the iodoaminoacid distribution within these goiters still revealed the antithyroid action of AG, whereas 48 hr after labeling the distribution of the tracer on chromatograms was hardly any different from that usually reported for goiters produced by moderate iodine deficiency. Double labeling experiments using 125I, administered with the drinking water for 50 days, and 131I injected in a single shot on day 49, showed the thyroidal 125I content (and thus 127I) to be far below control level in spite of the higher 131I uptake. Since the 131I-PBI was also elevated, it is assumed that enhanced iodine release outweighed the increased iodide clearance in chronically AG treated rats. Judging from normal growth and failure of stable serum PBI to drop during AG feeding, the animals always remained euthyroid. These findings are tentatively explained by the assumption that iodothyronine formation from iodotyrosine residues is more effectively inhibited by AG than any other step of hormone synthesis. An increase in TSH secretion compensates for the AG effect. TSH acceleratesevery single step of hormone synthesis ahead of the “coupling reaction.” Thus, a typical pattern of a euthyroid iodine deficiency goiter can be produced by an antithyroid drug without any concomitant iodine deficiency. (Endocrinology87: 905, 1970)