Abstract 192: Clinical and Genetic Profiling of Index Patients with Multiple Endocrine Neoplasia Type 2 Syndrome and Screening for Medullary Thyroid Carcinoma in Asymptomatic First-degree Relatives

Background: Multiple endocrine neoplasia type 2 (MEN2) syndrome is a rare disorder with autosomal dominant inheritance, characterised by the presence of two of the following three endocrine manifestations: medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and primary hyperparathyroidism (PHPT). There is a paucity of data on clinical and genetic profile of MEN2 syndrome in the Indian subcontinent. Objectives: We aimed to evaluate the clinical and genetic profile of index patients with MEN2 syndrome and perform screening for MTC among asymptomatic family members of such patients. Materials and Methods: This was an ambispective study conducted in the department of Endocrinology at AIIMS New Delhi, involving diagnosed patients of MEN2 syndrome between January 2016 and November 2022. MTC screening was performed with measurement of serum calcitonin levels (normal: <10 pg/ml) among family members of index patients. Results: We evaluated a total of 23 index patients with MEN2 syndrome (MEN2A, n=18; MEN2B, n=5). Data were derived retrospectively for 18 patients (MEN2A, n=14; MEN2B, n=4) and prospectively for 5 patients (MEN2A, n=4; MEN2B, n=1). Of the study patients, 16 (MEN2A, n=13; MEN2B, n=3) were females. The mean age at presentation in the two groups was 33 years and 22 years, respectively. Among patients with MEN2A syndrome, 11 (61%) presented with PCC and were synchronously detected to have MTC, while 7 (39%) presented with MTC, of whom 5 metachronously developed PCC. We noted PHPT in 3 (16%) patients with MEN2A syndrome. A total of 177 eligible family members of index patients with MEN2A syndrome were contacted, of whom 83 turned up for screening and 42 (50.6%) had elevated serum calcitonin levels (>10 pg/ml). Of the 5 patients with MEN2B syndrome, 4 (80%) presented with synchronous MTC and PCC and 1 (20%) presented with MTC alone. Of the 26 eligible family members of index patients with MEN2B syndrome, only 9 could be screened and all had normal serum calcitonin levels (<10 pg/ml). Metastatic MTC was noted in 3 (17%) patients with MEN2A syndrome and 3 (60%) patients with MEN2B syndrome Mutational analysis data are available for 7 index MEN2A and 4 MEN2B patients. The most common mutations in MEN2A and MEN2B groups were C634R (exon 11 of RET gene, n=5) and M918T (exon 16 of RET gene, n=4), respectively. Conclusions: MEN2 syndrome should be suspected in patients with MTC and young-onset PCC and all first-degree relatives of index patients with this syndrome should be screened appropriately.