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  • Title: Simulations of radioiodine exposure and protective thyroid blocking in a new biokinetic model of the mother-fetus unit at different pregnancy ages.
    Author: Rump A, Hermann C, Lamkowski A, Abend M, Port M.
    Journal: Arch Toxicol; 2022 Nov; 96(11):2947-2965. PubMed ID: 35922584.
    Abstract:
    In the case of nuclear incidents, radioiodine may be released. After incorporation, it accumulates in the thyroid and enhances the risk of thyroidal dysfunctions and cancer occurrence by internal irradiation. Pregnant women and children are particularly vulnerable. Therefore, thyroidal protection by administering a large dose of stable (non-radioactive) iodine, blocking radioiodide uptake into the gland, is essential in these subpopulations. However, a quantitative estimation of the protection conferred to the maternal and fetal thyroids in the different stages of pregnancy is difficult. We departed from an established biokinetic model for radioiodine in pregnancy using first-order kinetics. As the uptake of iodide into the thyroid and several other tissues is mediated by a saturable active transport, we integrated an uptake mechanism described by a Michaelis-Menten kinetic. This permits simulating the competition between stable and radioactive iodide at the membrane carrier site, one of the protective mechanisms. The Wollf-Chaikoff effect, as the other protective mechanism, was simulated by adding a total net uptake block for iodide into the thyroid, becoming active when the gland is saturated with iodine. The model's validity was confirmed by comparing predicted values with results from other models and sparse empirical data. According to our model, in the case of radioiodine exposure without thyroid blocking, the thyroid equivalent dose in the maternal gland increases about 45% within the first weeks of pregnancy to remain in the same range until term. Beginning in the 12th pregnancy week, the equivalent dose in the fetal thyroid disproportionately increases over time and amounts to three times the dose of the maternal gland at term. The maternal and fetal glands' protection increases concomitantly with the amount of stable iodine administered to the mother simultaneously with acute radioiodine exposure. The dose-effect curves reflecting the combined thyroidal protection by the competition at the membrane carrier site and the Wolff-Chaikoff effect in the mother are characterized by a mean effective dose (ED50) of roughly 1.5 mg all over pregnancy. In the case of the fetal thyroid, the mean effective doses for thyroid blocking, taking into account only the competition at the carrier site are numerically lower than in the mother. Taking into account additionally the Wolff-Chaikoff effect, the dose-effect curves for thyroidal protection in the fetus show a shift to the left over time, with a mean effective dose of 12.9 mg in the 12th week of pregnancy decreasing to 0.5 mg at term. In any case, according to our model, the usually recommended dose of 100 mg stable iodine given at the time of acute radioiodine exposure confers a very high level of thyroidal protection to the maternal and fetal glands over pregnancy. For ethical reasons, the possibilities of experimental studies on thyroid blocking in pregnant women are extremely limited. Furthermore, results from animal studies are associated with the uncertainties related to the translation of the data to humans. Thus model-based simulations may be a valuable tool for better insight into the efficacy of thyroidal protection and improve preparedness planning for uncommon nuclear or radiological emergencies.
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