Thyroid-stimulating hormone receptor gene mutations and polymorphisms in thyroid disease

Since thyroid-stimulating hormone receptor (TSHR) gene mutations were first detected in autonomously hyperfunctioning thyroid adenomas, considerable progress has been made in defining the role of genetic alterations of the TSHR in thyroid diseases regarding the receptor domains and the amino acid residues involved in mutations responsible for the altered (gain or loss) receptor function; the structure-function relationship based on the in vitro assessment of the different signal transduction pathways activated by the TSHR; the involvement of TSHR alterations in the development of thyroid malignancies; and the functional role and the frequency of TSHR mutations occurring in thyroid disorders. This review summarizes recent findings concerning the localization and the functional role of the naturally occurring TSHR gene mutations in thyroid diseases.