Does Genotype-Specific Phenotype in Patients with Multiple Endocrine Neoplasia Type 2 Occur as Current Guidelines...

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Multiple Endocrine Neoplasia type 2 (MEN2) is a hereditary condition characterized by medullary thyroid cancer (MTC), pheochromocytoma (PCC), and primary hyperparathyroidism (PHPT).
• Clinical manifestations are linked to specific pathogenic variants in the RET proto-oncogene.
• Optimal management strategies require understanding genotype-phenotype correlations.

Purpose of the Study:

• To retrospectively analyze genotype-dependent clinical manifestations in a large cohort of MEN2 patients.
• To compare observed clinical profiles with existing evidence-based knowledge.
• To inform optimal therapeutic and preventive strategies, including prophylactic thyroidectomy and clinical follow-up.

Main Methods:

• Retrospective single-center study of 158 MEN2 patients diagnosed and/or treated between 1990 and 2022.
• Categorization of patients based on their specific pathogenic RET proto-oncogene variant.
• Documentation of disease clinical manifestation and timing of occurrence.

Main Results:

• The study's findings largely align with existing literature on MEN2 clinical manifestations.
• A notably lower incidence of pheochromocytoma (PCC) was observed in patients with V804M/L RET mutations compared to predictions.
• Genotype-specific patterns of MTC, PCC, and PHPT were documented.

Conclusions:

• The study reinforces the importance of pathogenic RET variant-specific management in MEN2.
• Findings support current recommendations for tailored therapeutic and surveillance approaches based on genetic profile.
• Understanding genotype-phenotype correlations is crucial for optimizing patient care in MEN2 syndrome.