The Physiologic Activity of Tetrabrom-Thyronine and Tetrachlorthyronine*

METABOLIC equilibrium in the body, as far as thyroid hormone is concerned, is maintained by the balance between two actions of this hormone, namely, its effects in stimulating the metabolism of tissues on the one hand and in depressing the function of the thyroid gland on the other. The latter effect is brought about in two ways: a) indirectly, by depressing the output of thyrotropic hormone from the pituitary gland, and b) directly, by depressing the activity of the thyroid follicles (Cortell and Rawson, (1)). Several investigators have already utilized this property of thyroid hormone to depress the overactive thyroid of Graves' disease. Unfortunately, the high calorigenic action of the hormone makes its use in large dosage over a long period of time hazardous. The ideal compound for the control of the overactive thyroid would be one which retained the depressant effects on the thyroid and anterior pituitary gland shown by thyroxine, while having lost the property of stimulating tissue metabolism. The use of one such compound became possible, when, during our reinvestigation of the calorigenic activity of the optical isomers of thyroxine, it was found that most of the activity of racemic thyroxine resides in the laevo compound (Fig. 1). The activity of d-thyroxine, as shown in Figure 2, is relatively low, namely, about one tenth that of l-thyroxine. It was then suggested by Dr. Means that we use d-thyroxine to treat patients with Graves' disease. Unfortunately, the supply of d-thyroxine was limited and the problem could not be pursued further.