During the clinical study and treatment of a group of patients with thyroid carcinoma, we have studied the effects of thyroid hormone on several metabolic systems under conditions in which the thyroid status of the patients could be controlled at will. Early in the tracer studies of iodoalbumin metabolism in these patients it was apparent that it was necessary to employ a mathematical approach somewhat different from published methods of compartment analysis. Accordingly a suitable mathematical approach was developed by one of the present authors (1). In this report, the practical difficulties encountered in application of the approach to experimental data and the theoretical implications of the approach are discussed.The kinetic analysis of the data of a single tracer study comprises the body of the report. Additional data from other tracer studies are included only insofar as they contribute to the development of the model chosen for analysis. METHODSGeneral. The methods of dialysis of the commercial 1131 labeled human serum albumin employed and details of the injection procedure, collection of blood and urine samples, quantitation of radioactivity in urine and plasma, determination of serum albumin and quantitation of total radioactivity removed in blood sampling have been given elsewhere (2). Stool collections were made only in the case of M. H. in Experiment III. The individual specimens were suspended in concentrated sodium hydroxide and distilled water to known volume, allowed to digest partly, and then agitated until a uniform pipettable mixture was obtained. The counting procedure was the same as that for urine and plasma (2). None of the patients studied showed albuminuria No chemical fractionation of label was done routinely on urine or plasma samples.

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A method for the measurement of subnanogram quantities of iodine is described. Procedural detail and precision of results are presented for application of the method to protein-bound or total iodine in duplicate on 12.3 µl serum. Following wet ashing with chloric reagent, the iodine-catalyzed cerate-arsenite reaction was carried out at temperatures between 23 and 27°, and the reaction rate coefficients were corrected to refer to 25.0° by an empirical equation. The recovery of iodine standards, added to the precipitated protein before ashing, ranged between 96 and 106%. One contributing cause of this variation is the formation of an inhibitor of unknown nature during heating. Samples were brought to a final volume of 180 µl prior to fading. The detection limit was of the order of 0.04 ng iodine. For 62 serum samples having a mean iodine content of 0.558 ng (range 0.15-1.31 ng), the standard deviation calculated from duplicates was 0.019 ng/180 µl. For 31 samples having a mean iodine content of 2.24 ng (range 1.61-2.96 ng), the standard deviation was 0.039 ng/180 µl. Expressed as micrograms of iodine per 100 ml of serum, the mean ± standard deviation for the group of 62 samples was 4.54 ± 0.15.

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