Familial medullary thyroid carcinoma: Clinical variability and low aggressiveness associated with RET mutation at codon 804

Francesca Lombardo, Eric Baudin, Eusebio Chiefari, Franco Arturi, Stephane Bardet, Bernard Caillou, Chiara Conte, Bruno Dallapiccola, Dario Giuffrida, Jean Michel Bidart, Martin Schlumberger, Sebastiano Filetti

Research output: Contribution to journalArticlepeer-review

Abstract

Sixty-one heterozygotes harboring the germline V804L mutation of the RET protooncogene were identified in five independent families. A total of 31 subjects underwent surgery. Histology identified C cell hyperplasia in 30 cases, isolated in 12 and associated with medullary thyroid carcinoma (MTC) in 18. Six patients with MTC had lymph node metastases. Among the 14 patients with basal detectable calcitonin (CT) level, 12 had MTC and 2 had isolated C cell hyperplasia. In most individuals carrying 804 RET mutation, C cell disease displayed late onset and an indolent course; a pentagastrin test was negative in the majority of heterozygotes during the first 2 decades and was positive in only half of them during the third and fourth decades of life. Interestingly, concomitant somatic M918T was detected in a 12-yr-old girl with MTC and was likely to be responsible for both the early clinical appearance and the aggressiveness of the disease. Our data show that in these gene carriers, surgery may be postponed to the fourth decade of life or until the pentagastrin stimulation test becomes positive. Indeed, our data should be confirmed on a larger series of V804L carriers, but may offer a balanced strategy to keep under control and prevent development of the full disease phenotype.

Original languageEnglish
Pages (from-to)1674-1680
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number4
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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