The temporary nature of the inhibitory action of excess iodine on organic iodine synthesis in the normal thyroid.

IN 1944, Morton et al. observed that when 300 mg. of sheep thyroid slices were incubated in 3 cc. of a bicarbonate-Ringer medium to which various amounts of I as inorganic iodide had been added, inhibition of thyroxine and diiodotryosine formation occurred when the added I exceeded 20 gamma. The resemblance of this in vitro effect to the action of excess iodide in Graves' disease in man led us to investigate this phenomenon in the normal intact thyroid (Wolff and Chaikoff, 1948a). In addition to confirming the inhibitory action of excess iodide upon thyroxine synthesis in intact thyroids, the investigation showed that such inhibition by a single injection of iodide was related to the level of plasma iodine (Wolff and Chaikoff, 1948b). So long as the concentration of plasma iodine exceeded 20-35 gamma per cent, organic binding of iodine failed to occur in the gland, and only when the concentration fell below this critical range did the gland resume its function of depositing iodine in an organic form. These observations in rats have been confirmed recently by Stanley (1948). Evidence of an inhibitory action of excess iodide on thyroid function has also been obtained by a different approach. Purves and Griesbach (1946) have shown in rats that excess iodide (one mg. per day) potentiates the antithyroid action of a weak goitrogen. The administration of thiourea alone resulted in a slight degranulation of the acidophils of the anterior pituitary. But when large amounts of iodide were given along with the thiourea, the anterior pituitary presented a picture typical of complete thyroidectomy, i.e., complete degranulation of the acidophils. Mackenzie (1947) also has observed that the antithyroid effect of another weak goitrogen, sulfaguanidine, is augmented in rats fed a diet containing 500 gamma of iodine per gram. It is well known that in the thyrotoxic patient, administration of excess iodide results in a return of the hyperplastic gland to a more