Toxic Effects of Antithyroid Drugs *

The first studies on thiourea in this department were undertaken for reasons quite apart from the purposes for which it is now used. It had been reported that this compound distributed itself uniformly throughout the fluids of the body, that it was excreted like urea and could be recovered in the urine, completely, unchanged.31 These characteristics, if they could be verified, would make thiourea an ideal means of measuring the total volume of water in the body. When the subject was investigated by Purple and Lavietes," it was discovered that large doses of thiourea, 6 to 10 gm., induced severe nausea and vomiting with malaise, but no other discernible symptoms. Measurements of its volume of distribution and excretion yielded values that lent plausibility to the idea that it diffused freely through all the water and escaped destruction. Subsequently it was found that in somewhat smaller doses it produced offensive halitosis. Because of its untoward effects it was evident that the compound must be given in smaller doses if it was to be used for physiological studies. This required the development of a more sensitive analytical technique. A procedure was, therefore, devised which permitted measurements of the desired accuracy when doses of about one-tenth the former magnitude were used.' When such doses, 0.5 gm., were injected into dogs, it proved impossible to recover the whole of the injected dose in the urine.' A small fraction appeared to be disposed of in some manner. This had not been detected in the earlier studies because this fraction was so small in proportion to the large doses that had been given. With this quantity of thiourea the dogs, with the exception of one which invariably vomited, exhibited no untoward signs or symptoms, and postmortem examinations of animals who died from other causes incident to the experiments revealed no lesions that could be attributed to any untoward actions of the drug. Obviously thiourea was unsuited to the purpose for which it had been intended-measurement of the total fluid of the body. It could be inferred from its incomplete recovery