Advances in risk-oriented surgery for multiple endocrine neoplasia type 2

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Genetic association studies for Multiple Endocrine Neoplasia type 2 (MEN2) were historically biased by overrepresentation of highly penetrant mutations and advanced disease.
• This led to aggressive surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy, increasing morbidity.

Purpose of the Study:

• To describe the paradigm shift in MEN2 management over the past 25 years.
• To highlight the benefits of early identification and biochemical surveillance in asymptomatic MEN2 carriers.
• To outline refined, risk-oriented surgical approaches for MEN2.

Main Methods:

• Review of clinical insights and management strategies for MEN2 over the past 25 years.
• Analysis of the impact of early identification and biochemical surveillance on surgical decision-making.
• Evaluation of mutation-specific and age-dependent penetrance of associated endocrine tumors.

Main Results:

• A paradigm shift occurred from prophylactic organ removal to biochemical surveillance and targeted resection.
• Early identification of MEN2 carriers creates a 'window of opportunity' for less morbid interventions.
• Current approaches include pre-emptive thyroidectomy, tissue-sparing adrenalectomy, and parathyroidectomy limited to enlarged glands.

Conclusions:

• Refined management strategies for MEN2 have significantly reduced morbidity and mortality.
• Future research should focus on mutation-specific penetrance to further optimize risk-stratified care.
• The goal is to eliminate death and major morbidity from MEN2 within this generation.