A Family with Multiple Endocrine Neoplasia Type 2A: Importance of Early Prophylactic Thyroidectomy

Background: Medullary thyroid cancer (MTC) is a rare thyroid tumor originating from parafollicular C cells and constitutes about 5-10% of all thyroid cancers. There are 2 types including sporadic and familial MTC. In children and adolescents, MTC is usually familial and is caused by autosomal dominantly-inherited RET mutations. It may occur as a part of MEN 2A and MEN 2B syndromes or as isolated familial MTC. Calcitonin and carcinoembryonic antigen (CEA) can be used as tumor markers. MEN 2A is characterized by MTC (100%), pheochromocytoma (20-50%), and hyperparathyroidism (20-30%). In the presence of an individual with MEN2A, first-degree relatives and other family members must be screened for RET mutations, because early diagnosis and treatment are important for prognosis.
Aim: In this case report, we present a 5.6-year-old male who was identified to have heterozygous p.c634y (c.1901 G>A) mutation in the RET proto-oncogene when he was 2.5 years old.
Methods: A 5.6-year-old asymptomatic male was admitted because of family history of MEN 2A. His past medical history was unremarkable. Parents were not related.
Results: Physical examination revealed normal findings without any signs of goiter, thyroid nodule, or lymphadenopathy. Thyroid function was normal, serum calcitonin was <2 pg/mL, CEA was 1.65 ng/mL; parathyroid hormone, calcium and 24-hour urinary metanephrine-normetanefrine-epinephrine and norepinephrine levels were within normal limits. Thyroid ultrasonography revealed normal findings. Prophylactic total thyroidectomy was performed owing to the high-risk mutation in the RET proto-oncogene. Histopathological examination of the thyroid gland revealed medullary microcarcinoma focuses.
Conclusion: When a family history of MEN 2A syndrome is present, (i) clinical follow-up of asymptomatic individuals with serum levels of tumor markers is not safe; (ii) all family members should be screened with molecular analysis of the RET proto-oncogene; (iii) early prophylactic thyroidectomy should be performed after the assignment of risk group according to the result of molecular analysis.