{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:18:47Z","timestamp":1783487927631,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,6,28]],"date-time":"2013-06-28T00:00:00Z","timestamp":1372377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Reviewing the clinical outcomes of a large kindred with a <jats:italic><jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content><\/jats:italic> p.<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>ly533<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>ys mutation, 10\u00a0years after the first description of this kindred, has provided an important set of clinical data for healthcare decision\u2010making.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Patients<\/jats:title><jats:p>We identified 728 <jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content>533 Brazilian relatives, spread out over 7 generations. We performed clinical examination, biochemical and imaging analyses in the proband and in 103 carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurement and Results<\/jats:title><jats:p>The proband has been followed without evidence of structural disease in the last 10\u00a0years but with elevated calcitonin. The clinical and surgical features of 60 thyroidectomized <jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content>533 relatives were also described. Forty\u2010six patients had <jats:styled-content style=\"fixed-case\">MTC<\/jats:styled-content> (21\u201372\u00a0years), and 11 patients had <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010cell hyperplasia (<jats:styled-content style=\"fixed-case\">CCH<\/jats:styled-content>) (5\u201342\u00a0years). Twelve <jats:styled-content style=\"fixed-case\">MTC<\/jats:styled-content> patients with lymph node metastases had a tumour size of 0\u00b77\u20132\u00b78\u00a0cm. Calcitonin level and <jats:styled-content style=\"fixed-case\">CEA<\/jats:styled-content> were correlated with disease stage, and none of the patients presented with an altered <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content> or metanephrine. A 63\u2010year\u2010old woman developed pheochromocytoma and breast cancer. Two other <jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content>533 relatives developed lung squamous cell carcinoma and melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A vast clinical variability in <jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content>533 presentation was observed, ranging from only an elevated calcitonin level (3%) to local metastatic disease (25%). Many individuals were cured (42%) and the majority had controlled chronic disease (56%), reinforcing the need for individualized ongoing risk stratification assessment. The importance of this update relies on the fact that it allows us to delineate the natural history of <jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content> 533 <jats:styled-content style=\"fixed-case\">MEN<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> 10\u00a0years after its first description.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12264","type":"journal-article","created":{"date-parts":[[2013,6,8]],"date-time":"2013-06-08T08:24:42Z","timestamp":1370679882000},"page":"235-245","source":"Crossref","is-referenced-by-count":10,"title":["A ten\u2010year clinical update of a large <i><scp>RET<\/scp><\/i> p.<scp>G<\/scp>ly533<scp>C<\/scp>ys kindred with medullary thyroid carcinoma emphasizes the need for an individualized assessment of affected relatives"],"prefix":"10.1111","volume":"80","author":[{"given":"Priscila S.","family":"Signorini","sequence":"first","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Inez C.","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleber P.","family":"Camacho","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan C.","family":"Lindsey","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via O. F.","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa S.","family":"Kasamatsu","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto L.","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila P.","family":"Salim","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosana","family":"Delcelo","sequence":"additional","affiliation":[{"name":"Department of Pathology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana O.","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo (ICESP) Faculdade de Medicina da Universidade de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janete M.","family":"Cerutti","sequence":"additional","affiliation":[{"name":"Department of Morphology and Department of Genetics Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus R.","family":"Dias\u2010da\u2010Silva","sequence":"additional","affiliation":[{"name":"Department of Medicine Laboratory of Molecular and Translational Endocrinology Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui M. 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