Hypothyroidism due to bi-allelic variants in IYD: description of four families and a novel variant.

Bi-allelic loss-of-function variants in the IYD gene cause hypothyroidism resulting from iodine wasting. We describe eight patients (from four families in which the parents are first cousins) who are homozygous for a variant in IYD (including a novel missense deleterious variant, c.791C>T (P264L), in one family). Seven patients presented between 5 and 16 years of age with a large goiter, overt hypothyroidism and a high serum thyroglobulin. The goiter subsided with levothyroxine therapy in most. Upon stopping levothyroxine in five patients, goiter and hypothyroidism reappeared in three. In these three patients, a rising serum thyroglobulin concentration preceded hypothyroidism and goiter and urinary iodine excretion was low. In patients who remained euthyroid, urinary iodine was normal. In conclusion, these patients bearing bi-allelic pathogenic variants in IYD developed a large goiter, a high serum thyroglobulin and overt hypothyroidism when their iodine intake was low.