The Effect of Diiodotyrosine on the Basal Metabolism in Myxedema 1

Abstract

Much speculation has developed concerning the role of diiodotyrosine in the thyroid, particularly since the report of its isolation from the gland by Harington and Randall (1) in 1929. According to these authors, the iodine of the thyroid is about equally divided between diiodotyrosine and thyroxine and diiodotyrosine is to be regarded as the precursor of thyroxine. Observations on the biological effects of diiodotyrosine had been started some years before their report. Strouse and Voegtlin (2) in 1909 did not notice any clinical improvement following the administration of 0.1 gram three times a day for ten days and two weeks to a patient with myxedema and to a cretin respectively. Knipping and Wheeler-Hill (3) gave 100 mgm. of diiodotyrosine daily by mouth for several weeks to men and observed no effect on the basal metabolism, pulse, weight, or vegetative nervous system. Hoffmann (4) gave 3, 5, diiodo-1-tyrosine subcutaneously to normal men in total doses varying from 100 mgm. in one day to 8.4 grams in fourteen days and he likewise observed no effect on the basal metabolism. Beumer and Kornhuber (5) gave 19.5 grams of diiodotyrosine over an eight-day period to a four year old child and noted no influence on diuresis or weight. In a two year old cretin, who had improved greatly on thyroid, a relapse occurred when they gave from 0.5 to 1.0 gram of diiodotyrosine three times daily for eight weeks. The only contradictory observation appears to be that of Abderhalden (6), who reported beneficial results from feeding 3, 5, diiodo-1-tyrosine to three children (siblings) who all showed well marked symptoms of myxedema.As in the case of man, the data reported on lower animals do not furnish satisfactory evidence of a thyroid-like action of diiodotyrosine. Strouse and Voegtlin (2) observed that it was without effect on the nitrogen metabolism and blood pressure in dogs. Abelin (7) and Gaddum '(8) reported that it did not increase the metabolism of normal rats. Abderhalden and Wertheimer (9) showed that while thyroxine reduced the weight rapidly in rabbits and guinea pigs, diiodotyrosine had only a