When is prophylactic thyroidectomy indicated for patients with the RET codon 609 mutation?

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Multiple endocrine neoplasia type 2A (MEN2A) is caused by RET proto-oncogene mutations.
• Prophylactic thyroidectomy is typically recommended before age 5 for MEN2A.
• The optimal timing for thyroidectomy in patients with RET codon 609 mutations is unclear due to later disease onset.

Purpose of the Study:

• To evaluate the clinical presentation and optimal timing of thyroidectomy in a family with a RET C609Y mutation.
• To reassess current recommendations for prophylactic thyroidectomy in MEN2A patients with specific RET mutations.

Main Methods:

• Analysis of clinical, laboratory, and pathological data from 16 family members who underwent thyroidectomy.
• Literature review of reported cases involving RET codon 609 mutations.

Main Results:

• In the studied family, medullary thyroid carcinoma (MTC) was diagnosed in 9/16 patients (mean age 44.7 years), with 6 having lymph node metastases.
• C-cell hyperplasia (CCH) was observed in two patients at ages 18 and 37.
• Literature review indicated MTC onset in affected individuals around age 42 and CCH around age 24.

Conclusions:

• The youngest MTC diagnosis in patients with RET C609Y mutation was 21 years old.
• The youngest CCH diagnosis was 15 years old.
• These findings suggest that thyroidectomy can be delayed until ages 10-15 for RET C609Y mutation carriers, with annual calcitonin screening.