Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 2 is an autosomal dominant polyglandular cancer syndrome. It arises as a result of a germline mutation of the RET proto-oncogene. The aim of this study was to evaluate the aggressiveness of medullary thyroid carcinoma (MTC) in patients with a proven germline mutation in codon 634 RET proto-oncogene, the occurrence of other associated diseases and survival analysis.

Methods: The retrospective study included 66 patients, 26 probands and 40 family members, with a confirmed germline mutation in codon 634 RET proto-oncogene. The stage of the disease was determined on the basis of pathohistological findings after surgery for MTC, imaging studies before and after surgery, as well as determination of levels of serum tumor markers.

Results: In the total population of subjects (probands and family members), median age at diagnosis of MTC was 34.18±16.02 years. In the group of probands, carriers of Cys634Arg mutation were diagnosed in younger age compared to carriers of Cys634Phe (31.87 ± 5.01 vs 46.5±4.12 years, p 0.035). Metastatic disease was verified in 28.6% of probands and 21.6% of family members. In both groups, the disease was most often diagnosed in stage 2. No statistically significant difference was found between the preoperative levels of calcitonin and CEA between the groups (p 0.762, P 0.937). The occurrence of disease recurrence was statistically significantly more frequent in probands (p 0.034). In family members who underwent prophylactic thyroidectomy, no MTC was found in two patients at the age 4 and 14, but both had C-cell hyperplasia. The presence of pheochromocytoma was verified in 71% of subjects during follow-up, more often in probands (p 0.004). Median age at diagnosis was 40.90±14.10 years. In 64% of patients with pheochromocytoma tumor was bilateral. The type of mutation in codon 634 did not significantly affect the occurrence of pheochromocytoma (p 0.732). There was no statistically significant difference in the prevalence of primary hyperparathyroidism between the groups (p 0.165). Survival was significantly shorter in patients with stage 4 disease at the time of diagnosis compared to other stages of the disease (p 0.005).

Conclusion: The results obtained in this study indicate the need for early testing of family members of patients in order to enable timely prophylactic thyroidectomy, or to diagnose medullary thyroid cancer or pheochromocytoma at the earliest stage when the possibility of cure is greatest, or to avoid catastrophic consequences of catecholamine excess.