A New Method for the Measurement of Acute Alterations in Thyroxine Deiodination Rate in Man

A newly devised dual labeled iodine isotopic method is described for the detection and quantitation of alterations in thyroxine (T(4)) deiodination rate in man. This method employs the principle of a constant (125)I infusion to serve as a reference source for the generation of (131)I derived from the deiodination of T(4)-(131)I. Measurement of these two iodide isotopes are made in serially timed urine collections and are expressed in terms of a ratio value. Using this technique, it was possible to measure accurately the effects of a single dose of 6-propylthiouracil (6-PTU) in producing inhibition of T(4) deiodination in euthyroid subjects. It was also possible to assess the time of onset, duration of action, and degree of inhibition produced by 6-PTU. Employing single doses of 6-PTU, ranging from 100 to 1000 mg, there was found to be a log dose relationship with a degree of inhibition observed in T(4) deiodination. In control studies T(4) deiodination rate was found to be constant for periods ranging up to 72 hr in normal ambulating subjects. The acute administration of many other agents was employed in an attempt to alter the T(4) deiodination rate. These included diphenylhydantoin, methimazole, triiodothyronine, thyroxine, thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH), hydrocortisone, predinsolone, potassium iodide, epinephrine, and oxytocin. No detectable change in T(4) deiodination rate was observed with these agents in the dosage ranges employed in this study. The lack of any observable alteration in the T(4) deiodination rate in response to this array of drugs and hormones appears to indicate that the availability of T(4) to intracellular sites of deiodination and possibly action is well modulated to resist abrupt changes.