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Prophylactic thyroidectomy in multiple endocrine neoplasia type 2.

Friedhelm Raue1,2, Karin Frank-Raue1

  • 1a Endocrine Practice and Molecular Laboratory, Brückenstr. 21, 69120 Heidelberg, Germany.

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|February 21, 2019
PubMed
Summary

Medullary thyroid carcinoma (MTC), a key part of multiple endocrine neoplasia type 2 (MEN 2), arises from RET gene mutations. Early RET-mutation testing guides prophylactic thyroidectomy, improving prognosis for hereditary MTC.

Keywords:
proto-oncogenecalcitoningenotype–phenotype correlationmedullary thyroid carcinomamultiple endocrine neoplasia type 2prophylactic thyroidectomy

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Area of Science:

  • Oncology
  • Genetics
  • Endocrinology

Background:

  • Medullary thyroid carcinoma (MTC) is a primary manifestation of multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominant disorder.
  • MEN 2 is etiologically linked to activating mutations in the RET proto-oncogene.
  • Disease progression in RET-mutation carriers involves a spectrum from C-cell hyperplasia to MTC, influenced by specific mutations.

Purpose of the Study:

  • To elucidate the genotype-phenotype correlations in RET-mutation carriers.
  • To establish risk stratification for MTC development and progression.
  • To underscore the importance of early RET-mutation analysis for hereditary MTC management.

Main Methods:

  • Analysis of RET proto-oncogene mutations in affected individuals.
  • Documentation of age-related progression from normal C-cells to MTC.
  • Correlation of specific RET mutations with disease penetrance, aggressiveness, and clinical presentation.

Main Results:

  • A strong genotype-phenotype correlation exists, dictating neoplastic development timelines and disease aggressiveness.
  • Specific RET mutations stratify individuals into distinct risk levels for MTC.
  • Early-stage MTC diagnosis through RET-mutation analysis is crucial for favorable outcomes.

Conclusions:

  • RET-mutation analysis is essential for identifying individuals at risk for hereditary MTC.
  • Understanding genotype-phenotype correlations enables personalized risk assessment and management strategies.
  • Prophylactic thyroidectomy timing, guided by risk stratification, significantly improves the prognosis of MTC.