Our data suggest that in biallelic TG mutation, thyroid stimulating hormone (TSH)-driven iodination underlies inefficient T4 formation derived from the iodoproteome of dead thyrocytes. In the presence of homozygous mutant TG or in the complete absence of TG, normalizing circulating T4 requires massive goiter growth to generate sufficient cells to sustain this inefficient hormonogenesis mechanism.
Young et al. (2026) studied this question.