@ December 1967 ADULT HYPERTHYROIDISM tion does exist in man. Certainly, it has been shown that if you have a patient with a tube in the bile duct and give thyroxine, a certain amount will come out in thebile, in the form of both conjugated and unconjugated T,. Only very cursory attempts have been made, but, certainly, no thyroxine binding substance is present in human bile. To what extent the thyroxine may be reabsorbed, I am not certain, because I don’t think, when one has a tube in a bile duct, one can conclude that the quantity of thyroxine entering thebile is the same as that which would enterif the patient did not have a tubein the bile duct. Also, there are abnormalities in normal binding which occur in sick patients which might influence hepatic uptake and secretion, but I have no basis for an accurate estimate of this. if @v® KENNETH STERLING, Depart“% ment of Medicine, Bronx Veterans Administration Hospital, New York: Our information in man is limited. It appears that, in experimental rats, the amount of thyroxine conjugated as glucuronide and the amount of T; conjugated as sulfate are quite appreciable. It appears to be less in human subjects. I don’t doubt that the phenomenon has clinical significance in states of hepatic impairment. We do know in thyrotoxicosis that there may be impairment of liver glycogen stores. I think, however, this is more for future investigation than for present comment. DR. INGBAR: There is no evidence that the proportion of hormone that comes out in the stool of thyrotoxic patients is appreciably different than in euthyroid patients. Of course, the quantity coming out is larger, but the proportion is not different. Thus, this does not suggest that there exists some detoxifying or excretory mechanism of particular physiological impor- tance. @ DR. WERNER: Theliver is subject to a degree of functional injury in hyperthyroid- sOTSEO4 1771 ism. as shown by decrease in serum albumin and rise in serum globulin, as well as by a change in BSP excretion. Is it possible, with increasing liver damage, that there might then occur a change in function of the enterohepatic circulation? DR. INGBAR: Swiss workers found that there was an element of this in patients with acute, severe liver disease, acute viral hepatitis, as I recall. They suggested there was evidence of diminished conjugation in the biliary secretion. DR. WERNER: Couldthis result in backing up, with a rise in the level of total and hence of free thyroxine? DR. INGBAR: It would raise the PBI, but whether this is due to a backing up phe- nomenon is not clear because they found that thyroxine binding globulin was increased. I am sure they didn’t have any direct measurements of free thyroxine. DR. McKENZIE: I could add that we found in various disorders of the liver, mainly cirrhosis, TBG can be elevated. In at least one of the patients, we made independent studies which showed a high circulating level of estrogen, so that the TBG may be elevated on this account. TBG may also be markedly diminished, however, and not infrequently TBPA may be diminished, so a variety of changes can occur with injury to theliver. DR. WERNER: TBPA levels decrease in liver disease. Therefore, does the increase in TBG level indicate that there is a reciprocal relationship between the two proteins, and, if so, how is a change in one protein detected by the regulatory mechanism for the other? DR. McKENZIE: I would say that, except for hepatic disease, one sees a reciprocal relationship under most circumstances. Dr. Braverman and Dr. Ingbar have shown that in normal males and