Iodide is essential for the synthesis of thyroid hormones. Due to its scarcity in most environments it is critical that we can conserve and recycle the iodide we obtain in our diets. Monoiodotyrosine and diiodotyrosine are produced by the synthesis of triiodothyronine and thyroxine; however only a small fraction of these residues are used. Iodide is released from the remainder by the enzyme iodotyrosine deiodinase, and can then be reused. This paper describes how defects in the DEHAL1 gene encoding iodotyrosine deiodinase can lead to a failure to recycle iodide and thus result in severe goitrous hypothyroidism.

The main article describes the investigation of four patients, including two siblings, with hypothyroidism, goitre and other features suggestive of iodotyrosine deiodinase deficiency. All four were born to consanguineous parents. Two patients had undergone neonatal screening and had a normal thyroid-stimulating hormone (TSH) at that time. There was considerable variation in the age of onset of hypothyroidism and in outcome. Six coding exons of DEHAL1 were amplified by polymerase chain reaction, the products were purified and sequenced, and three mutations were identified. Functional analysis revealed that all three mutations dramatically reduced the deiiodination of the iodotyrosines, but suggested that each may act in a different way to produce this effect.

Moreo et al. confirm that the gene DEHAL1 encodes iodotyrosine deiodinase, and that mutations in this gene result in hypothyroidism due to the loss of iodide. The authors speculate that the variation in phenotype and age of onset may be due in part to the availability of dietary iodide. This reinforces the importance of efforts to eradicate iodine deficiency worldwide. This paper also emphasizes that hypothyroidism can have a congenital cause despite normal TSH levels at neonatal screening. The accompanying editorial provides an excellent description of thyroid hormone synthesis and iodide recycling.