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Iodine in the Therapy of Graves' Disease: A Century After Henry S. Plummer

2023; Mary Ann Liebert, Inc.; Volume: 33; Issue: 3 Linguagem: Inglês

10.1089/thy.2023.0068

1557-9077

Peter Kopp,

Thyroid Cancer Diagnosis and Treatment

I n this issue of Thyroid, Uchida et al. present a mouse model of Graves' hyperthyroidism generated by immunization of BALB/c mice with the human thyrotropin receptor A-subunit. 1 The investigators then compared the serum thyroxine (T4) and triiodothyronine (T3) levels, the intrathyroidal content of iodothyronines, as well as expression profiles of genes involved in thyroid hormonogenesis and secretion in untreated mice (GD-C) and mice treated with inorganic iodide (GD-NaI).Unimmunized BALB/c mice were used as controls.The results document a normalization of the serum T4 and T3 levels in the GD-NaI mice, whereas GD-C mice continued to have elevated serum concentrations relative to unimmunized mice.Compared with unimmunized mice, GD-C mice had higher intrathyroidal concentrations of T3, reverse T3 (rT3), and T4.In the GD-NaI mice, the mean intrathyroidal T4 and rT3 concentrations were roughly twofold higher in comparison with the GD-C mice.Transcriptome analyses showed an upregulation of genes coding for proteins involved in thyroid hormone synthesis, transport processes, and redox balance in the GD-C mice.In contrast, treatment with iodine inhibited the upregulation of these genes in the GD-NaI mice.More specifically, GD-C mice showed an upregulation of key genes such as Tshr, Tpo, Dio1, and the thyroid hormone transporter Slco4a1 compared with controls.In GD-NaI mice, genes such as Slc5a5 (Nis), Slc26a4 (pendrin), Tpo, Duox2 and Duoxa2, Dio1, and Slco4a1 were downregulated, whereas Dio3 was upregulated.The data document that treatment with inorganic iodide results (1) in a decrease in thyroid hormone synthesis, (2) a decrease in thyroid hormone secretion, (3) an intrathyroidal increase of T4 and rT3, and (4) a normalization of serum T3 and T4.In aggregate, these studies add additional mechanistic details on the effects of inorganic iodide in Graves' disease, 1 a treatment that has been introduced a century ago by Henry S. Plummer (1874-1936; see Fig. 1, also cover figure of this