Endocrine Abstracts

JOINT2284

RET mutations drive the development of multiple endocrine neoplasia (MEN) syndromes, including medullary thyroid carcinoma (MTC) and pheochromocytoma. We present three families with distinct RET mutations, revealing the complex clinical spectrum and hereditary patterns. The findings underscore the neccesity of early genetic screening and diagnosis. A male patient, aged 18 in 1977, was diagnosed with MTC. At that time, he underwent a subtotal thyroidectomy, as it was the standard procedure. In 2005, he required a total thyroidectomy due to disease recurrence, and again in 2014 for a further recurrence. Additionally, the patient was diagnosed with pheochromocytoma and primary hyperparathyroidism. Genetic testing in 4 out of 13 of his family revealed the presence of a RET mutation (c.1900 T>C, p. Cys634Arg, exon 11), in 3 members across 4 generations (one is asymptomatic), 1 being negative. The second family carries a germline RET mutation (c.1852T>C, p. Cys618Arg, exon 10) which was identified through testing a 43-year-old female patient, initially diagnosed with MTC. She underwent a total thyroidectomy, but with minimal residual disease and secondary lymphatic metastases. Genetic testing in 7 out of 21 family members across 3 generations revealed 5 positive for the same RET mutation (2 asymptomatic), including her two daughters (one of whom has MTC, and the other had MTC and pheochromocytoma), as well as in a nephew diagnosed with Hirschsprung disease, 2 being negative. The third family we are presenting carries a RET mutation (c.1902C>G, p. Cys634Trp, exon 11), identified in a 52-year-old male patient who initially presented with symptoms suggestive of pheochromocytoma, subsequently confirmed and surgically resected. The patient also has a diagnosis of MTC. Genetic testing in this family revealed the same RET mutation in his daughter (who has MTC ) and his nephew (who has bilateral pheochromocytoma and MTC). In this family, across 2 generations, 8 out of 30 family members were tested: 6 were positive, 2 negative. From those postive, 2 were asymptomatic, while other 2 presented only MTC, and 2 MTC+Pheo. In conclusion, these families highlight the critical role of looking for RET mutations in the development of multiple endocrine neoplasia and related disorders. The diverse clinical manifestations observed—such as MTC, pheochromocytoma, and hyperparathyroidism—underscore the importance of genetic screening and family history evaluation for early diagnosis and proper management. Early detection, appropriate surveillance, and genetic counseling are key to improving outcomes and preventing further complications in affected families.