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
Article first published online: 28 JUN 2013
© 2013 John Wiley & Sons Ltd
Volume 80, Issue 2, pages 235–245, February 2014
How to Cite
Signorini, P. S., França, M. I. C., Camacho, C. P., Lindsey, S. C., Valente, F. O. F., Kasamatsu, T. S., Machado, A. L., Salim, C. P., Delcelo, R., Hoff, A. O., Cerutti, J. M., Dias-da-Silva, M. R. and Maciel, R. M. B. (2014), 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. Clinical Endocrinology, 80: 235–245. doi: 10.1111/cen.12264
- Issue published online: 8 JAN 2014
- Article first published online: 28 JUN 2013
- Accepted manuscript online: 8 JUN 2013 03:08AM EST
- Manuscript Accepted: 4 JUN 2013
- Manuscript Revised: 17 MAY 2013
- Manuscript Revised: 21 JAN 2013
- Manuscript Received: 27 DEC 2012
- São Paulo State Research Foundation/FAPESP. Grant Numbers: 2006/60402-1, 2010/51547-1, 2006/54922-2
- Fleury Group. Grant Number: 12518
- FAPESP. Grant Number: 2009/50575-5
Reviewing the clinical outcomes of a large kindred with a RET p.Gly533Cys 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 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 10 years but with elevated calcitonin. The clinical and surgical features of 60 thyroidectomized RET533 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 RET533 relatives developed lung squamous cell carcinoma and melanoma.
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 10 years after its first description.