Thyroid, iodide, and the NIS transporter

January is Thyroid Awareness Month, a time to highlight the vital role of the thyroid gland in our body’s health. Resembling a butterfly and nestled in the neck, the thyroid is key to regulating our metabolism. It produces hormones like thyroxine (T4) and triiodothyronine (T3), which govern metabolic processes vital to our survival—from regulating heart rate and body temperature to influencing the growth and development of our brains.

Central to the thyroid’s hormone production is a key micronutrient called iodide because its oxidized form, iodine, is an essential constituent of the thyroid hormones. Without iodide, our thyroid simply cannot produce its hormones. Look at the table salt you have in your kitchen; big chances are it is iodized, providing you with this essential nutrient. Apart from iodized salt, iodide is also found in various foods, like seafood or dairy products, and it’s quite important to ensure adequate iodide intake to keep your thyroid busy producing its essential hormones.

But how does iodide get into the thyroid? It appears that the key player in this process is the Sodium/Iodide Symporter (NIS). This plasma membrane transporter is the thyroid’s gateway for iodide, moving it from the bloodstream into the thyroid follicular cells. NIS couples the inward translocation of iodide against its electrochemical gradient to the inward transport of sodium down its electrochemical gradient. Remarkably, unlike chloride channels and transporters, which transport both chloride and iodide, NIS preferentially transports iodide, even though the concentration of chloride in the extracellular medium is over 105 times that of iodide. Mutations in the SLC5A5 gene, encoding NIS, cause iodide transport defects, which, if left untreated, lead to congenital hypothyroidism and consequent cognitive and developmental deficiencies. Therefore, the proper functioning of NIS in our thyroids is crucial for our health.

Having said that, it’s important to note that NIS can’t distinguish between regular and radioactive iodide, released for example during nuclear power plant disasters like Chernobyl and Fukushima. In such scenarios, the thyroid can accumulate the radioactive variant, potentially leading to thyroid cancer. This is where potassium iodide tablets become a lifesaver. By saturating the thyroid with “good” iodide, these tablets prevent the absorption of the harmful variant, significantly reducing the risk of thyroid cancer.

This property puts NIS at the center of the remarkably successful treatment for thyroid cancer based on radioiodide, administered after thyroidectomy: this therapy targets remnant malignant cells and metastases that actively accumulate the radioisotope via NIS. Furthermore, there is now great interest in overexpressing NIS in non-thyroidal tumors that do not natively express NIS, to employ similar radioiodide-based therapy.

In summary, Thyroid Awareness Month highlights the critical role of the thyroid gland and iodide in our overall health, underscoring the importance of ongoing research to combat thyroid-related diseases.