title: Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma.
abstract: Thyroid carcinomas, even when well differentiated, usually appear as hypofunctioning at scintigraphy. We report a case of an aggressive insular thyroid carcinoma presenting as an autonomously functioning thyroid nodule and causing severe thyrotoxicosis. The tumor was metastatic to a cervical lymph node and both lungs. An activating mutation of the TSH receptor gene in both the primary tumor and the lymph node metastasis was found, due to a base substitution at codon 633 (normal guanine at position 1896 replaced by cytosine CAC for GAC causing aspartic acid substitution by histidine). Other known oncogenes (gsp, ras, PTC/ret, trk, met, and p53) were not involved. This is the first description of an activating TSH receptor mutation in a thyroid hyperfunctioning carcinoma in which an aggressive malignant phenotype coexisted with activation of the cAMP cascade and differentiated thyroid functions.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Cattedra di Endocrinologia, University of Reggio Calabria, Catanzaro, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Russo
authors.forename: S
authors.initials: S
authors.lastname: Tumino
authors.forename: F
authors.initials: F
authors.lastname: Arturi
authors.forename: P
authors.initials: P
authors.lastname: Vigneri
authors.forename: G
authors.initials: G
authors.lastname: Grasso
authors.forename: A
authors.initials: A
authors.lastname: Pontecorvi
authors.forename: S
authors.initials: S
authors.lastname: Filetti
authors.forename: A
authors.initials: A
authors.lastname: Belfiore
mesh_terms: D001483:Base Sequence; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D005260:Female; D005796:Genes; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011877:Radionuclide Imaging; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D013971:Thyrotoxicosis / Q000209:etiology
chemical_list: D011989:Receptors, Thyrotropin