Determination of the Rates of Accumulation and Loss of Iodide and of Protein-Binding of Iodine in the Human Thyroid Gland

The thyroid gland may be described in terms of an open three-compartment model, with serum iodide, thyroid iodide and thyroid protein-bound iodine pools. Three kinetic parameters describe this model: the unidirectional clearance, C, of radioiodide into the thyroid iodide pool from the serum, the exit rate constant, kTB, determining the escape of iodide from the thyroid iodide pool to the serum before binding occurs, and the binding rate constant kb. A new method of analysis is presented which for the first time allows the calculation of these three kinetic parameters in man from observed values of thyroid radioiodine uptake and serum radioiodide activity. A simple iterative computer program is used which adjusts the values of kTB, kb and C until the sum of squares of differences between the calculated and observed radioiodine uptakes is a minimum, within predetermined limits of precision. The thyroid radioiodine uptake was determined at intervals during a period of hours in 15 hyperthyroid and 7 euthyroid subjects by quantitative scintiscanning. The serum radioiodide concentration was determined from venous blood samples withdrawn during this period. In each case, the unidirectional clearance and exit rate constant for iodide and the binding rate constant for iodine were calculated. No statistically significant difference was found between the calculated and observed values of thyroid radioiodine uptake, implying that the model is a satisfactory representation of thyroid radioiodine accumulation during the time interval used in these studies. The values of C and kb were found to be significantly greater in the hyperthyroid than in the euthyroid subjects. No significant difference was found in the value of kTB for the two groups. The hyperthyroid subjects were found to convert trapped iodide more efficiently to protein-bound iodine than the euthyroid subjects. Determination of the serum inorganic 127I concentration has enabled the quantity of iodine in the thyroid trapped iodide pool to be estimated. This quantity was not significantly different in the two groups of subjects. Possible uses of this new test of thyroid function in the diagnosis of thyroid dysfunction and in assessing the nature and extent of suppression of thyroidal uptake of iodine by antithyroid drugs are discussed. (author)