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A ten‐year clinical update of a large RET p. G ly533 C ys kindred with medullary thyroid carcinoma emphasizes the need for an individualized assessment of affected relatives
Author(s) -
Signorini Priscila S.,
França Maria Inez C.,
Camacho Cleber P.,
Lindsey Susan C.,
Valente Flávia O. F.,
Kasamatsu Teresa S.,
Machado Alberto L.,
Salim Camila P.,
Delcelo Rosana,
Hoff Ana O.,
Cerutti Janete M.,
DiasdaSilva Magnus R.,
Maciel Rui M. B.
Publication year - 2014
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12264
Subject(s) - medicine , proband , calcitonin , pheochromocytoma , lymph node , medullary thyroid cancer , carcinoma , thyroid carcinoma , oncology , disease , thyroid , hyperplasia , endocrinology , gastroenterology , mutation , biochemistry , chemistry , gene
Summary Objective Reviewing the clinical outcomes of a large kindred with a RET p. G ly533 C ys mutation, 10 years 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 RET 533 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 10 years but with elevated calcitonin. The clinical and surgical features of 60 thyroidectomized RET 533 relatives were also described. Forty‐six patients had MTC (21–72 years), and 11 patients had C ‐cell hyperplasia ( CCH ) (5–42 years). Twelve MTC patients with lymph node metastases had a tumour size of 0·7–2·8 cm. 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 RET 533 relatives developed lung squamous cell carcinoma and melanoma. Conclusions A vast clinical variability in RET 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 RET 533 MEN 2 A 10 years after its first description.