Elevated basal serum levels of calcitonin and simultaneous surgery of MEN2A-specific tumors

Abstract

Background Multiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome caused almost by germline RET mutation, and characterized by medullary thyroid carcinoma (MTC), in combination or not with pheochromocytoma (PHEO), hyperparathyroidism (HPTH), cutaneous lichen amyloidosis (CLA) and Hirschsprung’s disease (HD). The basal serum calcitonin (Ctn)/carcinoembryonic antigen (CEA) levels are significantly correlated with MTC stage. Metachronous surgery of MEN2A-specific tumors is a routine procedure. We aimed to explore the clinical significance of pro-gastrin-releasing peptide (proGRP) in MTC with elevated Ctn, and simultaneous surgery of MEN2A-specific tumors. Methods We retrospectively investigated 8 RET mutation carriers of 2 Chinese pedigrees with MEN2A. Clinical profiles, imaging examinations, preoperative and postoperative biochemical data, surgical procedures and follow-up records were evaluated. Results Three patients showed the levels of elevated Ctn, but normal proGRP. Among them, one patient (FAIII-6) in Family A (one for RET C634R mutation), diagnosed with bilateral MTC, left PHEO, bilateral HPTH and CLA, classified as MEN2A-related CLA subtype, underwent successfully simultaneous adrenal-sparing surgery (ASS), total thyroidectomy (TT) and parathyroidectomy, while TT of the other two patients (FBII-3 and FBIII-7) diagnosed with bilateral MTC in Family B (all for RET C618R mutation) were performed. Unexpectedly, absence of neck lymph node MTC metastasis was indicated by histopathological examination. Postoperatively, all had consistently “undetectable” or normal levels of Ctn/CEA during follow-up. Conclusions Patients with normal proGRP, despite high levels of Ctn, might have noregional lymph node MTC metastasis, and neck dissection should be avoided. Moreover, simultaneous surgery for coexistent PHEO, and either MTC or HPTH is an approach of choice to use as an alternative treatment pattern. Recognition of MEN2A-related CLA and subsequently early screening of RET mutation may be favorable for timely management of MEN2A-specific tumors.