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To investigate the mechanism of the increased plasma estradiol levels in spontaneous hyperthyroidism, the contribution, by peripheral conversion, of androstenedione and testosterone to the circulating estrogens was determined. The conversion ratio of androstenedione to estrone was significantly increased in both males and females (0.0396 and 0.0256, respectively). The conversion ratio of androstenedione to estradiol was increased in the male (0.0094) but not in the female (0.0051) patients. The conversion ratio of testosterone to estrone was increased in both males (0.0072) and females (0.0070). The conversion of testosterone to estradiol, however, was not increased in either sex. The plasma concentration of androstenedione was significantly increased (0.34 μg/100 ml) in the male patients with hyperthyroidism. However, the production rate of androstenedione was increased in both sexes (8.59 and 6.72 mg/day). The contribution of testosterone and androstenedione to plasma estrone and estradiol (product of conversion ratio and plasma concentration of precursor) was significantly increased in the men and women with hyperthyroidism. Thus, the increased estrogen levels in spontaneous hyperthyroidism results in large part, from increased peripheral conversion rather than by direct glandular secretion. The pharmacologic induction of hyperthyroidism in a patient with panhypopituitarism suggests that the increased androgen-estrogen conversion is a direct effect of thyroid hormone manifested mainly by the increased conversion of androstenedione to the estrogens.