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

Abstract

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.

Keywords: age-dependent tumor development; medullary thyroid carcinoma; multiple endocrine neoplasia type 2A; pheochromocytoma; preventative surgery; primary hyperparathyroidism.