The Changing Face of Multiple Endocrine Neoplasia 2A: From Symptom-Based to Preventative Medicine

Context: Early genetic association studies yielded too high risk estimates for multiple endocrine neoplasia (MEN2A), suggesting a need for extended surgery. Objective: The objective was to delineate temporal changes in MEN2A presentation by birth cohort analyses. Methods: Birth cohort analyses (10-year increments; <= 1950 to 2011-2020) of carriers of rearranged during transfection (RET) mutations who underwent surgery for MEN2A. Results: Included in this study were 604 carriers (155 index, 445 nonindex, 4 additional patients), with 237 carriers harboring high-risk mutations, 165 carriers moderate-high risk mutations, and 202 carriers low-moderate risk mutations. With increasing recency of birth cohorts, there was a continual decline in index patients from 41-74% to 0% (P <.001) and of medullary thyroid cancer (MTC) from 96-100% to 0-33% (P <.001). Node metastases diminished from 62-70% to 0% (P <= .001; high and low-moderate risk mutations), whereas biochemical cure after thyroidectomy surged from 17-33% to 100% (P <= .019; high and low-moderate mutations). Surgical interventions for MEN2A-related tumors were performed increasingly earlier, causing median carrier age to fall: from 51-63 to 3-5 years at thyroidectomy (P <.001); from 46-51 to 24-25 years at first adrenalectomy (P <= .013; high and moderate-high risk mutations); and from 43.5-66 to 16.5-32 years at parathyroidectomy. MTC diameters were more effectively decreased from 14-32 to 1-4 mm (P <= 002) than pheochromocytoma diameters (nonsignificant). Conclusion: These insights into MEN2A presentation, adjusted by birth year, illustrate the shift from reactive to preventative medicine, enabling less extensive risk-reducing surgery.

Automated summary

The presentation of MEN2A has changed over time, with earlier surgical interventions and a shift towards preventative medicine. This has resulted in reduced risk and improved outcomes for patients.