Session: FP35-Neoplasia of Endocrine Tissues
Bench to Bedside
Room 122 (Moscone Center)
Poster Board MON-293
INTRODUCTION: Multiple Endocrine Neoplasia type 2 A (MEN 2 A) is a syndrome caused by germline activating mutations in the RET proto-oncogen. Genotype-phenotype correlation has been described, and there are codons-specific guidelines, but information about single nucleotide genotype-specific clinical risk profiles is scarce, and it could be useful for tailoring more precise clinical care.
OBJECTIVE: To study the clinical presentation of a large number of MEN2A patients with the specific Cys634Tyr (C634Y) RET mutation.
METHODS: Data from the Spanish MEN national online database from January 2009 to December 2011 was analyzed, focusing on patients with C634Y mutation.
RESULTS: Our series comprises 172 carriers from 48 unrelated kindreds. 169 patients have thyroid disease: C-cell hyperplasia was diagnosed in 25 patients at a mean age of 8.4±6.3(0.5-28.6) years and 144 subjects had medullary thyroid cancer (MTC) at a mean age of 32.9±32.8 (4–75) years. Lymph node metastases were observed in 26 patients at a mean age of 37.8±15.8 (16.5-75.1) years and 5 patients had also distant metastases aged 34–63.70 (40.69%) patients had pheochromocytoma (PHEO) detected at a mean age of 40.8±38.4 (16.4-77.3) years. At the moment of diagnosis 57% had bilateral tumors and 50% had symptoms related with PHEO. Bilateral adrenalectomy was performed in 35 patients. One of them was diagnosed with recurrent disease due to a paraganglioma 16 years after the first operation. 29 patients underwent an unilateral adrenalectomy, one of them had persistent disease and 4 patients had recurrence at a mean interval of 7.2±7.1 (3-18) years. 4 patients had hyperparathyroidism (HPT) at a mean age of 40.1±34.6 (18-73) years. Age-related penetrance for MTC was 46% by age 30 and 85% by age 50, for PHEO age-related penetrance was 29% by age 30 and 80% by age 50.
CONCLUSIONS: These data provide C634Y RET specific neoplastic risk and age-related penetrance profiles in a large number of patients. This information could suggest that the optimal timing for prophylactic thyroidectomy might be before five years old. Screening for PHEO could be initiated at the age of twelve years and should be intensified at the age of 20 to 50 years. Unilateral adrenalectomy is a reasonable option in patients with unilateral adrenal involvement because it has a low rate of recurrence in the long term. Take into account the low penetrance for HPT; screening for it could be initiated also at twelve years at 3-5 year intervals.
Nothing to Disclose: NV, JT, EN, PP, LF, SG, JM, AC, LS, VS, JAD
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
See more of: Abstracts - Orals, Featured Poster Presentations, and Posters