Constitutively activating mutations of the thyrotropin receptor and thyroid disease

Recent advances in the understanding of the molecular biology of the TSH receptor had a considerable impact on several aspects of thyroidology. Identification and functional characterization of somatic mutations in the TSH receptor gene that activate the receptor ligand-independently. Provide an explanation for the molecular pathomechanisms of solitary toxic thyroid adenomas. Moreover, we have recently demonstrated, that multiple hyperfunctioning adenomas in the same thyroid gland can be caused by identical or different somatic Thyrotropin receptor mutations. Furthermore, germline mutations with similar characteristics have been reported in the TSH receptor gene of families with autosomal dominant forms of non-autoimmune hyperthyroidism and in two cases of sporadic congenital non-autoimmune hyperthyroidism. Interestingly, constitutively activating Thyrotropin receptor alterations have also been identified in differentiated thyroid carcinoma, thus implying a possible role of the constitutively active TSH receptor in the aetiopathology of both benign and malignant thyroid neoplasia.