A family of multiple endocrine neoplasia type 2A (Sipple's syndrome)

Abstract

We reported a family of multiple endocrine neoplasia type 2A (Sipple's syndrome) extending over three generations.A 23-year-old man and his younger brother aged 19 visited to our hospital to take screening examination for multiple endocrine neoplasia (MEN) 2A because their grandmother, father and uncle had been diagnosed as MEN 2A and had undergone surgical removal of adrenal pheochromocytoma and medullary thyroid carcinoma (MTC) in our hospital ten years before.The two patients had no symptoms, and blood counts and routine blood chemistry tests showed normal levels. The levels of serum calcitonin were high in both cases while carcinoembryonic antigen was increased only in the younger brother. Although we could not palpate an thyroid tumor in either case, computerized tomographic (CT) scans of the neck demonstrated a calcification in the right thyroid lobe in the elder patient and obvious bilateral thyroid tumors with calcifications in the younger.Both urinary excretion and plasma concentration of catecholamines in either case remained normal. CT scans of their abdomen demonstrated normal adrenal glands. DNA sequence analysis of the RET proto-oncogene revealed a single point mutation, TGC (Cys) to TAC (Try), in codon 634 of exon 11, in each case.They were diagnosed as MTC without pheochromocytoma, and total thyroidectomy was performed. The diagnosis of MTC was confirmed histologically.The detection of missense mutations in the RET proto-oncogene is very sensitive and useful method for genetic diagnosis of MEN2A and predicting its onset in affected family members. In our two cases, this technique was very helpful to early diagnosis of MEN2A.