We studied the effect of lithium on the release of T3, T4, and cAMP from perifused mouse thyroids and on cAMP content in thyroid pieces. Lithium significantly inhibited T3 and T4 release from TSH-stimulated mouse thyroids. This inhibitory effect on thyroid hormone release was dependent on the concentration of lithium. Under continuous stimulation with TSH and 3-isobutyl-1-methylxanthine, both cAMP release and cAMP content were significantly decreased by lithium. In addition, we studied the effect of lithium on (Bu)2cAMP-stimulated thyroid hormone release. T3 and T4 release was stimulated by (Bu)2cAMP in a similar way to TSH. Lithium significantly inhibited (Bu)2 cAMP-stimulated T3 and T4 release from perifused mouse thyroids. These results suggest that lithium inhibits the action of TSH in the thyroid gland by both suppression of cAMP production and inhibition at a step beyond cAMP generation.

In 29 patients with thyrotoxic Graves' disease treated with conventional long term antithyroid drug therapy, serum thyroglobulin (Tg) was serially determined by RIA and compared with clinical course, goiter shrinkage, and 131I uptake suppression. Those subjects with Tg autoantibody-negative sera comprised 46% of the patients with Graves' disease. They were divided into a remission group (G I) and an exacerbation group (G II). G I was subdivided into G Ia, who were in remission for 7-40 months, and G Ib, who relapsed more than 15 months after therapy. G II was still on therapy 27-62 months after its initiation, because these subjects exacerbated on reduction of the drugs. Goiter shrinkage occurred in 60% and 0%, and 131I uptakes were suppressed by T3 in 50% and 0% in G I and G II, respectively. Serum Tg in G I declined progressively and reached 48 +/- 5 (+/-SE) ng/ml on discontinuation of therapy, in sharp contrast with serum Tg in G II which remained high throughout (154 +/- 29 ng/ml at the last examination; P less than 0.001). Results of goiter shrinkage, 131I uptake suppressibility, and serum Tg levels were similar in G Ia and G Ib on cessation of therapy. Serum Tg levels less than 68 or more than 140 ng/ml on discontinuation of therapy were helpful in predicting the outcome of therapy. On the other hand, Tg levels were low and goiters were small in size in euthyroid Graves' disease. Tg levels were not clearly correlated with goiter weight or serum T4 and T3 levels before treatment. In conclusion, serial determinations of serum Tg reflect thyroid activity and provide information useful in the decision to discontinue therapy and observation after that.

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