1772 PANEL DISCUSSION ON HYPERTHYROIDISM females there is a difference, and that the females have a higher TBG than males, and one can plot graphs showing this reciprocal relationship, and I think, Dr. Werner, you showed—andJater with Dr. Oppenheimer—that administration of steroids gives rise to elevation of TBPA and diminution of TBG. The same thing can occur in acromegaly. In hepatic disease, on the other hand, apparently because of failure to synthesize these proteins, the normal reciprocal relation fails to hold. We don’t really know, although we are inclined to guess that TBPA may possibly be primary in this relationship, but it is very hard to say at this stage. DR. WERNER: Lest the patient problem belost in the discussion of pathogenetic mechanisms, I shall ask Dr. Maloof to say a word about the metabolism of some of the major antithyroid drugs and something about the mechanism of sensitivity to such agents. I shall then ask Dr. Conard to say a word about ‘I radiation effects on the thyroid. DR. FARAHE MALOOF, Department of Medicine, Massachusetts General Hospital, Boston: The metabolic studies we have carried out with the antithyroid drugs, primarily thiourea, have shown clearly that this drug is taken up by the thyroid in small amounts, about 1% of the administered dose/g thyroid, and that it is specifically metabolized by thyroid tissue (86). We have on the basis of our studies postulated a mechanism of action by which thiourea inhibits the iodination reaction (37). I think, to go back to the first panel (1) discussion, in which everybodystated that the antithyroid drugs passed through the placenta, this may not be completely valid because the only studies that have been done have been those with thiourea (88). Shepard demonstrated clearly that thiourea did go throughthe placenta of the du ES bub Volume 27 rat and was taken up and metabolized by the fetal rat thyroid. Whetherthis applies to other antithyroid drugs remains to be seen. Anotherpoint in regard to this problem is that, in animals given thyroxine, the uptake of the thiourea by the thyroid is greatly diminished. I suppose that someone, some day, should do this experimentin pregnant rats to see whether the administration of, thyroxine to the mother suppresses the transmission of the antithyroid drugs by the placenta, and hence suppresses the uptake by the fetal thyroid. This may have a very important bearing on the method which Herbst and Selenkow have advocated for treating pregnant women with hyperthyroidism, namely, thyroid along with antithyroid drugs in order to inhibit a fetal goiter (39, 40). None of the work that we have done would help in elucidating the mechanism by which these drugs produce sensitivity in some patients. DR. WERNER:Is there an explanation for hypersensitivity to sodium iodide? Allergic reactions of this magnitude have been recognized since early days. DR. INGBAR:Is there some special reason why you say iodide? That is what is given to the patient, but that is not necessarily what is producing the reaction. We know that if we give large doses of iodide to patients, there are iodinations which occur—probably iodinations of serum proteins, and perhaps other proteins. I think there are data in the immunologic literature which suggest that such iodinated protein does not havespecific immunologic properties and that there is a good deal of cross-reaction between a variety of iodinated proteins. This was studied a number of years ago. For example, antibodies to iodinated diphtheria toxin would react with iodinated albumin. Iodinated protein, certainly, is a good antigen, and hencethere 7