Purpose of review: Thyroid hormones are essential for normal development, growth, and metabolism. Their synthesis occurs in thyroid follicles and requires an adequate iodide supply and a sequence of regulated biochemical steps. The uptake of iodide into thyrocytes is well characterized, but its efflux at the apical membrane is poorly understood. This review discusses potential mechanisms underlying iodide efflux with emphasis on recent developments and controversies.
Recent findings: The functional characterization of pendrin (PDS/SLC26A4), a multifunctional anion exchanger, suggested that it could be involved in mediating iodide efflux. This is supported by the phenotype of patients with Pendred syndrome (deafness, goiter, partial iodide organification defect), which is caused by biallelic mutations in the SLC26A4 gene, as well as functional studies. However, apical iodide efflux is also possible in the absence of pendrin, implicating the presence of at least another channel. Recently, Anoctamin 1 (TMEM16A), a calcium-activated anion channel has been identified at the apical membrane of thyrocytes and functional studies suggest that it may play a predominant role in mediating iodide efflux.
Summary: Anoctamin and pendrin are two plausible candidates as mediators of apical iodide efflux. Their relative affinity for iodide and their exact physiological role await, however, further characterization.