Effect of iodine on early stage thyroid autonomy

Abstract

Thyroid autonomy is a frequent cause of thyrotoxicosis in regions with iodine deficiency. Epidemiological data suggest that iodide may influence the course of pre-existing thyroid autonomy. Making use of FRTL-5 cells stably expressing a constitutively activating TSH receptor mutation as an in vitro model of thyroid autonomy, we investigated the impact of iodide on proliferation, function and changes in global gene expression. We demonstrate that iodine inhibits growth in TSHR WT and L629F mutant FRTL-5 cells and downregulates e.g. protocadherin cluster (Pcdha1-13) and thyroid responsive element (Thrsp). In addition functional genes e.g. iodotyrosine deiodinase (iyd) and oncogen junB are upregulated, while sodium-iodide-symporter (Nis) and thyroid peroxidase (Tpo) are downregulated by iodide. Iodide tunes down the biological activity of autonomous thyrocytes and may thus be of therapeutic benefit not only to prevent the occurrence of somatic TSHR mutations, causing thyroid autonomy, but also to slow down the development of clinically relevant disease.

Apoptosis of NOD.H2h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

“…Highest overexpression (5.77-fold) was observed with the Tpo (thyroid peroxidase) gene. This contrasts with findings from previous studies reporting either no effect of iodide treatment on Tpo expression (23,39,40) or even downregulation of its expression (41,42) in thyroid cells or lines. The reasons for this discrepancy are unclear but may be due to the different protocols used.…”

Beneficial effects of adequate iodine supply on characteristics of thyroid autonomy

“…Iodide inhibited mutations of TSH receptor and therefore the occurrence and development of TA. 17 Our observation that the incidence of the euthyroid TA was relatively higher than the incidence of the hyperthyroid TA in 2009 compared with 1998 indicates that lasting adequate iodine supply probably protects thyroid gland from detrimental effects of iodine. Confronted with an acute iodine load, thyroid gland with sufficient iodine content reacts differently than the thyroid gland with low iodine content.…”

“…Iodine may have a protective role in this process as shown in vitro in a cell line of rat thyroid cells with the mutant TSH receptor. Iodide inhibited mutations of TSH receptor and therefore the occurrence and development of TA …”

“…In Slovenia, the intracellular iodine concentration was most likely lower in 1998 and the thyroid glands were more vulnerable to changes in iodine supply and more often developed hyperthyroidism after an iodine load than in 2009. Besides, in vitro studies indicated that a high concentration of iodide may inhibit proliferation of TA in the early phase . That might explain a slower transition from euthyroidism to hyperthyroidism in 2009 and a relatively lower incidence of hyperthyroid TA in 2009 than in 1998.…”

“…Besides, in vitro studies indicated that a high concentration of iodide may inhibit proliferation of TA in the early phase. 17 That might explain a slower transition from euthyroidism to hyperthyroidism in 2009 and a relatively lower incidence of hyperthyroid TA in 2009 than in 1998.…”