Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant disorder from a RET proto-oncogene mutation, characterized by the presence of medullary thyroid carcinoma (MTC), pheochromocytoma and/or primary hyperparathyroidism.

Materials and Methods: A retrospective study of 5 probands (3 males and 2 females, age range 31–46 years) and 6 family members (2 males and 4 females, age range 2–50 years) diagnosed as MEN 2A at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, during 2000–2015 was performed. Direct sequencing of the RET gene successfully identified all mutant alleles of the affected individuals. Demographic data, clinical profiles, mutation types and genotype-phenotype correlation were analyzed.

Results: At the diagnosis, four probands had pheochromocytoma and MTC whereas the other one developed all three. Of the pheochromocytoma, all of them were benign, 60% (3/5) were bilateral and 60% (3/5) were the presenting tumors. Two of the probands initially presented with MTC with multiple foci at the diagnosis. Hyperparathyroidism due to hyperplasia was identified in one case. All the affected subjects responded well to standard treatment of each tumor except one that was delayed in diagnosis resulting in fatal outcome. Two distinct mutations which all located in codon 634 of exon 11 in RET gene, C634S (60%) and C634R (40%), were detected. A prophylactic thyroidectomy based on a classification of RET mutations in an asymptomatic MTC 10-year-old girl was performed successfully.

Conclusions: Screening and early detection of MEN2A mutation carriers are very effective clinical intervention. As described in the literature, MTC is usually the first manifestation in patients with MEN 2A; however, pheochromocytoma may be the presenting tumor due to its alarming symptoms. In this study the identified frequent loci of the RET gene will facilitate the molecular diagnosis of MEN 2A in Thai patients.