CHANGES IN THYROIDAL FUNCTION DURING ADAPTATION TO LARGE DOSES OF IODIDE.

Abstract

Studies were conducted to determine the mechanism whereby the acute inhibitory effect of large doses of iodide on the organic binding of thyroidal iodide (Wolff-Chaikoff effect) is overcome during prolonged iodide administration (adaptation or escape phenomenon). Thyroids of control rats and of rats adapted to iodide in vivo were freed of inorganic iodide by in vivo administration of thiocyanate and in vitro leaching, and were then incubated in media containing inorganic I/sup 131/ of widely varying specific activity. In vitro, when exposed to low concentrations of extracellular iodide, thyroids of control animals accumulated and organically bound more iodine than did adapted glands. As the extracellular iodide concentration was increased, the total iodine accumulation in control thyroids increased; however, the quantity of iodine bound organically ultimately declined. At this point, ratios of labeled mono- to diiodotyrosine rose. Thus, a Wolff-Chaikoff effect was induced in vitro in control glands. In adapted thyroids, far less iodine entered the thyroid, but especially at higher concentrations of extracellular iodide, the percentage of accumulated iodide bound organically did not decline so rapidly as in controls. As a result, total organic binding rose progressively and, at high iodide concentrations in the medium, exceeded that in control glands.more » Mono- to diiodotyrosine ratios did not increase. Thus, escape from the inhlbitory effects of iodide was evident in vitro in adapted thyroids. At each concentration of extracellular iodide, far less inorganic iodide was found in adapted than in control glands, and the concentration of thyroidal iodide achieved by adapted thyroids at the highest medium iodide concentratl ons used was far less than that sufficient to induce the Wolff-Chaikoff effect in control glands. In the presence of blocking concentrations of methimazole, the iodidetransport capacity of adapted thyroids was far lower than that of control glands. Qualitatively similar data were obtained in studies of the thyroids of control and adapted hypophysectomized rats. Administration of thyroid-stimulating hormone to adapted rats did not alter their in vitro iodine metabolism, or their ability to resist the inhibitory effects of high concentrations of extracellular iodide. These data suggest that adaptation to the inhibitory effects of large doses of iodide occurs through an intrinsic thyroidal mechanism that reduces the thyroidal iodidetransport capacity and thereby allows intrathyroidal iodide to decline to concentrations insufficient to sustain the Wolff-Chaikoff effect. (auth)« less