The Use of Lithium in the Treatment of Thyrotoxicosis

Abstract

A B S T R A C T Since lithium has been showx%n to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thvrotoxicosis. Eight detailed "lI kinetic studies were performed on seven thvrotoxic women and data was analy,zed using a computer program. Lithium at serum levels of about 1 mEq 'liter decreased the loss of '31I from the thyroid, led to a fall in serum "II levels and diminished urinary "'I excretion. Coinputer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and( nonllormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serunm.Neither inhibition of release nor of hormone disappearance seemled to be affected by mlethimazole (release: 52% decrease without methimilazole, 60,% \w-ith mlethimazole; hormone disappearance: -60% decrease in both). Wlheni Li' was discontinued, recovery of the iodine release rate and hormiione disappearance rate over the observed time span -was variable, ranging from no recovery to rates that exceeded pre-Li' values. When Li' is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients wlho did not receive methimazole and 15-67%C in the methimazoletreated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction witlh Li'. The similarity of inhibition of iodine release from the thvroid produced by Li' and iodides is discussed.

The Effect of Tanespimycin (17-AAG) on Radioiodine Accumulation in Sodium-Iodide Symporter Expressing Cells

“…Compounds such as retinoic acid [20], valproic acid [21], and LY294002 [22] may induce increases in cellular iodide accumulation by enhancing NIS gene expressions via a variety of mechanisms. Chemicals that may reduce the efflux rates of iodine, such as lithium [23], DIDS, and tanespimycin [9,10] have also been recognized; however, the mechanisms relevant to such activities have not yet characterized in detail. Tanespimycin, a less liver toxic and more stable geldanamycin derivative [24] has been previously identified as a chemotherapeutic agent.…”

Hyperthyroidism—an unusual feature of thyroid carcinoma

“…9,10 Propranolol has the additional benefit of non-selective betareceptor blockade. 10 Lithium inhibits the release of thyroid hormone from the thyroid gland 11 and cholestyramine interferes with the enterohepatic circulation, of FT 4 and FT 3 . 12 Radioactive iodine therapy in the excessively thyrotoxic phase is not advisable, as mortality has been reported from further exacerbation of thyrotoxicosis.…”

Effects of Theophylline on Radioiodide Uptake in MCF-7 Breast Cancer and NIS Gene–Transduced SNU-C5 Colon Cancer Cells

“…[7][8][9][10][11][12][13] Lithium has been demonstrated to decrease the release of radioiodide from thyroid cells, thereby prolonging its effective half-life within thyroid cancer tissue of primary tumors, lymph nodes, and distant metastases. 14,15 More recently, it has been discovered that breast cancer cells frequently express endogenous NIS on the basolateral membrane with or without intracellular NIS, although they are generally associated with deficient radioiodide concentrating capacity. 16,17 Further, the cloning of the NIS gene and the availability of techniques to transfer this gene to cells that do not normally express the protein is promising to extend radioiodide therapy to various extrathyroid malignancies.…”