1770 PANEL DISCUSSION ON HYPERTHYROIDISM which we would consider to be distinctly rapid. A number of these relatives now-—— this was about ten years ago—have become thyrotoxic and have developed nonsuppressible thyroidal function. But they had abnormalities in iodine metabolism beforehand. DR. WERNER: I want to ask Dr. McKenzie a question. One of the evidences which has been cited to show that LATS may be the etiologic factor of Graves’ disease is the fact that it is present in the neonate, born of a hyperthyroid mother, and then disappears as the baby recovers. Now I understand your comments to indicate that you don’t think that LATS is a primary factor in this disorder. DR. McKENZIE: The concept I have at present is that LATSis a primary factor in the pathogenesis of the hyperthyroidism of Graves’ disease; regarding the etiology of the syndrome, however, I think we should consider that a genetic abnormality in immunetolerance, or a predisposition to the formation of autoantibodies, is a primary inherited factor. I certainly would not suggest that Graves’ disease is LATS and nothingelse. DR. KRISS: There are two other bits of evidence that might be mentioned here with respect to genetics. Dr. Mosier has reported finding LATSin the sera of some infants with mongolism. Tied in with that is Fialkow’s observation that infants with mongolism and their mothers have a higher incidence of antithyroglobulin antibody, and the mothers have a higherincidence of Hashimoto-type thyroiditis. Fialkow (33) is inclined to the view that the antibodies perhaps caused the chromosomal abnormality. We could conceive of an abnormality in a chromosomeas having something to do with a subsequent abnormality of the thyroid in children. Then, LATS might be thought of as arising from a form of genetically induced injury. Despite the presence of LATS, the infant SUF 2106 Volume27 with such a damaged gland may remain euthyroid. DR. WERNER: I don’t suppose one should quote unpublished data, but we obtained serum from four patients with mongolism at Letchworth Village and found no LATSin any. We should now go on to a recent observation by Dr. Helen Farran (34) which seemed quite interesting to me. When she fed tyrosine to patients with hyperthyroidism, she found that the serum PBI concentration rose. Dr. Farran attributed the increase in PBI to increased formation of iodotyrosine. DR. McKENZIE: Can we invite Dr. Werner to enlarge on that point? DR. WERNER:It is known that plasma after feed-@ 2 tyrosine levels become elevated ing of tyrosine to hyperthyroid patients or normal subjects after administration of triiodothyronine (35). Farran and Shalom (34) found that there is also an increase in serum PBI, due, they claim, to an increase in circulating lodotyrosines. The latter were separated by a fractionation method not yet published. The change in PBI was highly significant in three of the eight hyperthyroid patients. Unfortunately, the demonstration of the presence of iodotyrosines in serum in hyperthyroidism has been based on single dimension chromato- — graphic procedures, and has not been con- firmed by more sophisticated techniques, as far as I know. We cometo the next point, the role of the liver in the degradation of thyroxine, and the importance of the enterchepatic circulation of thyroid hormone in man, andits influence on the levels of serum thyroxine and thyroid hormone conjugates. I shall ask Dr. Ingbarif he would want | to say something about this, and Dr. -g Sterling. DR. INGBAR:I am not sure that we know . a | to what extent an enterohepatic circula- %