A mathematical model of human iodine metabolism.
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A specific, sensitive, and reproducible in vitro assay for antithyroid compounds and environmental goitrogens has been used to investigate antithyroid activity (AA) in small samples of water supplying 15 localities in endemic and nonendemic goiter areas of western Colombia. A significant positive correlation was observed between goiter prevalence and AA in water collected from the pipelines of these localities. Samples at the water source showed only borderline significance. No significant correlation was observed in waters between AA and total hardness (ppm) or concentrations of Ca, Mg, sulfates, chlorides, silicates, nitrates, and iodine. AA was also demonstrated by this in vitro assay in well water previously shown experimentally to be goitrogenic and that supplied the endemic goiter district of Candelaria town in western Colombia. In contrast, water from the well supplying the area of lower endemicity was found to possess little AA. These results provide experimental support for epidemiological observations that demonstrate a relationship between the sources of drinking water and goiter prevalence rates, and are consistent with previous findings indicating that organic antithyroid compounds contaminate water supplies in areas where goiter persists despite adequate iodine supplementation.
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Method developments are described for a iodine speciation method. This method is based on a reversed-phase liquid chromatography separation combined with inductively coupled plasma-mass spectrometry detection. Investigations are performed concerning the methanol tolerance/stability of inductively coupled plasma, postcolumn oxidation/volatilization of iodine from species, influences of buffer pH, and column temperature on separation efficiency. The experiments focused on six iodine species, namely iodine, monoiodothyrosine, di-iodothyrosine, tri-iodothyronine, reversed tri-iodothyronine, and thyroxin. Detection limits were determined between 0.08 and 1.5 microg/L (iodine related), dependent on species. Appplications on a urine sample were performed, showing iodide as the predominant iodine species.
Reversed-phase liquid chromatography-inductively coupled plasma mass spectrometric hyphenation was used for iodine speciation in human serum. First investigations showed that iodine species nearly quantitatively were eluted in the void volume. The result indicated that protein-linked thyroid hormones were not interacting with the stationary phase, thus being not retained. Investigations were performed about T4-TBG (thyroxin-thyroxin-binding globulin) complex generation and its retention during chromatography. It was shown that T4-TBG was not retained on the column. Therefore, a protease treatment was introduced for serum sample preparation. The analysis of "normal" sera (after protease) gave reasonable results lying in the range published in literature: I-:11; di-iodothyrosine (DIT): 2.1; mono-iodothyrosine (MIT): 1.6; reversed tri-iodothyronine (rT3): 3.9; T3: 5.9; T4: 60; each micrograms iodine per liter. The method also proved to recognize abnormalities in a pathologic serum, having rT3 as the predominant species. In this case the method obviously was superior compared to standard immunoassay methods, as it is monitoring the iodine in the species (physiologically active iodine species), whereas immunoassay methods may sometimes detect deiodinated (inactive) compounds.
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