{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:13:03Z","timestamp":1783555983384,"version":"3.55.0"},"reference-count":27,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1210\/jcem.82.3.3838","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:01:43Z","timestamp":1389200503000},"page":"735-738","source":"Crossref","is-referenced-by-count":5,"title":["Detection of an Activating Mutation of the Thyrotropin Receptor in a Case of an Autonomously Hyperfunctioning Thyroid Insular Carcinoma1"],"prefix":"10.1210","volume":"82","author":[{"given":"Diego","family":"Russo","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Sperimentale e Clinica, Cattedra di Endocrinologia, and Facolta\u0300 di Farmacia, Cattedra di Farmacologia (D.R.), University of Reggio Calabria, Catanzaro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Tumino","sequence":"additional","affiliation":[{"name":"Istituto di Clinica Medica I (S.T.), Catania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Arturi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale e Clinica, Cattedra di Endocrinologia, and Facolta\u0300 di Farmacia, Cattedra di Farmacologia (D.R.), University of Reggio Calabria, Catanzaro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Vigneri","sequence":"additional","affiliation":[{"name":"Istituto di Medicina Interna e di Malattie Endocrine e del Metabolismo, Cattedra di Endocrinologia (A.B., P.V.), University of Catania, Catania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Grasso","sequence":"additional","affiliation":[{"name":"Servizio di Anatomia Patologica, Ospedale S. Pietro e Gravina (G.G.), Caltagirone"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"Cattedra di Endocrinologia, Universita\u0300 Cattolica, Laboratorio di Oncogenesi Molecolare, Istituto Tumori Regina Elena (A.P.), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Filetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale e Clinica, Cattedra di Endocrinologia, and Facolta\u0300 di Farmacia, Cattedra di Farmacologia (D.R.), University of Reggio Calabria, Catanzaro"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Belfiore","sequence":"additional","affiliation":[{"name":"Istituto di Medicina Interna e di Malattie Endocrine e del Metabolismo, Cattedra di Endocrinologia (A.B., P.V.), University of Catania, Catania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614151121700_R1","author":"Pinsky","year":"1986"},{"key":"2020071614151121700_R2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/BF03349730","article-title":"The management of thyroid nodules.","volume":"18","author":"Belfiore","year":"1995","journal-title":"J Endocrinol Invest"},{"key":"2020071614151121700_R3","first-page":"4744","article-title":"Expression of thyroid specific transcription factors TTF-1 and PAX-8 in human thyroid neoplasm.","volume":"54","author":"Fabbro","year":"1994","journal-title":"Cancer Res"},{"key":"2020071614151121700_R4","first-page":"63","article-title":"Thyroid cancer presenting as a hot thyroid nodule: report of a case and review of the literature.","volume":"1","author":"Rubenfeld","year":"1988","journal-title":"Thyroidology"},{"key":"2020071614151121700_R5","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/00060793-199610000-00012","article-title":"Thyroid-stimulating hormone receptor gene mutations and polymorphism in thyroid diseases.","volume":"3","author":"Russo","year":"1996","journal-title":"Curr Opin Endocrinol Diabetes"},{"key":"2020071614151121700_R6","first-page":"1347","article-title":"Genetic alterations in thyroid hyperfunctioning adenomas.","volume":"80","author":"Russo","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614151121700_R7","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/0006-291X(89)92727-7","article-title":"Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor.","volume":"165","author":"Nagayama","year":"1989","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614151121700_R8","first-page":"488","article-title":"DNA sequencing with chain terminating inhibition.","volume":"82","author":"Sanger","year":"1977","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614151121700_R9","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1056\/NEJM198803243181206","article-title":"Thyrotoxicosis due to thyroid cancer: role of thyroid stimulating antibodies.","volume":"318","author":"Filetti","year":"1988","journal-title":"N Engl J Med"},{"key":"2020071614151121700_R10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF03347853","article-title":"Thyroid hormone-producing metastases in differentiated thyroid cancer.","volume":"19","author":"Gross","year":"1996","journal-title":"J Endocrinol Invest"},{"key":"2020071614151121700_R11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1055\/s-0038-1624342","article-title":"Jodinduzierte T3-Hyprthyreose beim metastasierenden follikularen Schilddrusenkarzinom.","volume":"25","author":"Ehrenheim Ch. 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