A ten-year clinical update of a large RET p.Gly533Cys kindred with medullary thyroid carcinoma emphasizes the need for an individualized assessment of affected relatives

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Signorini, Priscila S. ^[1] ; Franca, Maria Inez C. ^[1] ; Camacho, Cleber P. ^[1] ; Lindsey, Susan C. ^[1] ; Valente, Flavia O. F. ^[1] ; Kasamatsu, Teresa S. ^[1] ; Machado, Alberto L. ^[1] ; Salim, Camila P. ^[1] ; Delcelo, Rosana ^[2] ; Hoff, Ana O. ^{[1, 3]} ; Cerutti, Janete M. ^{[4, 5]} ; Dias-da-Silva, Magnus R. ^[1] ; Maciel, Rui M. B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Lab Mol & Translat Endocrinol, Dept Med, BR-04039032 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pathol, BR-04039032 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Escola Paulista Med, Dept Genet, BR-04039032 Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Escola Paulista Med, Dept Morphol, BR-04039032 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CLINICAL ENDOCRINOLOGY; v. 80, n. 2, p. 235-245, FEB 2014.
• Citações Web of Science: 7

Resumo

Objective Reviewing the clinical outcomes of a large kindred with a RET p.Gly533Cys mutation, 10years after the first description of this kindred, has provided an important set of clinical data for healthcare decision-making. Design and Patients We identified 728 RET533 Brazilian relatives, spread out over 7 generations. We performed clinical examination, biochemical and imaging analyses in the proband and in 103 carriers. Measurement and Results The proband has been followed without evidence of structural disease in the last 10years but with elevated calcitonin. The clinical and surgical features of 60 thyroidectomized RET533 relatives were also described. Forty-six patients had MTC (21-72years), and 11 patients had C-cell hyperplasia (CCH) (5-42years). Twelve MTC patients with lymph node metastases had a tumour size of 07-28cm. Calcitonin level and CEA were correlated with disease stage, and none of the patients presented with an altered PTH or metanephrine. A 63-year-old woman developed pheochromocytoma and breast cancer. Two other RET533 relatives developed lung squamous cell carcinoma and melanoma. Conclusions A vast clinical variability in RET533 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 RET 533 MEN2A 10years after its first description. (AU)

• Processo FAPESP: 10/51547-1 - Carcinoma medular de tiroide hereditario: percepcao e atitude de pacientes, familiares e profissionais de saude sobre questoes bioeticas.
• Beneficiário: Rui Monteiro de Barros Maciel
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/60402-1 - Carcinoma medular da tiróide: revisitação à clínica, à biologia molecular, à bioquímica e à biologia do desenvolvimento depois dos achados da genética molecular
• Beneficiário: Rui Monteiro de Barros Maciel
• Modalidade de apoio: Auxílio à Pesquisa - Temático