Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-Up
Yue-Ping Wang1, Fei-Ping Li2, Hui-Hong Wang3
1Department of Urology, The Affiliated Jinhua Hospital, Zhejiang University School of Medicine, 365 Renmin East Road, Jinhua 321000, Zhejiang Province, China.
Background:
Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by Medullary Thyroid Carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A.
Methods:
Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed.
Results:
In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and lessaggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO.
Conclusion:
Integrated RET screening, serum calcitonin, and plasma metanephrine/ normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.
Insights
Early RET genetic screening for Multiple Endocrine Neoplasia type 2A (MEN 2A) significantly improves outcomes for Medullary Thyroid Carcinoma (MTC) and pheochromocytoma (PHEO). This allows for earlier diagnosis and less aggressive disease management in RET C634 mutation carriers.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Multiple Endocrine Neoplasia type 2A (MEN 2A) is primarily caused by germline RET codon C634 mutations.
- MEN 2A is characterized by Medullary Thyroid Carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH).
- Early diagnosis and treatment are crucial for improving the long-term prognosis of MEN 2A.
Purpose of the Study:
- To evaluate the impact of early RET genetic screening on the clinical presentation and outcomes of MEN 2A.
- To analyze the effectiveness of standardized surgical approaches for MTC and PHEO in MEN 2A patients.
Main Methods:
- Genetic screening of RET codon C634 was performed on three index cases and 29 relatives from three families.
- Demographic, clinical, histopathologic, and follow-up data were systematically collected and analyzed.
- Comparison of clinical outcomes between symptomatic and asymptomatic MTC patients identified through screening.
Main Results:
- RET C634Y mutation was identified in 10 individuals (31.3%).
- Individuals identified through screening were diagnosed with MTC at a significantly younger age (18.1 vs. 39.0 years) and had less aggressive MTC (smaller size, lower lymph node positivity, lower recurrence rates).
- Pheochromocytoma (PHEO) occurred in 60% of carriers, with adrenal-sparing surgery demonstrating a low recurrence rate (16.7% over 10 years).
Conclusions:
- Integrated RET screening, serum calcitonin, and plasma metanephrine/normetanephrine levels aid in early diagnosis and standardized treatment of MTC and PHEO in MEN 2A.
- Laparoscopic adrenal-sparing surgery before total thyroidectomy is a preferred approach for PHEO in MEN 2A.
- Early detection through genetic screening significantly improves MTC and PHEO management and patient outcomes in MEN 2A.
