MON-450 Prophylactic Thyroidectomy in a Patient with Codon 891 Mutation of the RET Proto-Oncogene

Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumor of the parafollicular or C cells of the thyroid gland, accounting for 1-2% of thyroid cancers in the United States. About 25% MTCs are familial as a part of the MEN2 syndrome or familial MTC (FMTC). Germline mutations in codon 891 are predominantly associated with FMTC. Case: 65-year-old Caucasian male was referred to the Endocrinology clinic after bilateral thyroid nodules were found on thyroid US. The patient had requested an ultrasound of his thyroid after his brother was diagnosed with MTC following fine-needle aspiration for an incidental thyroid nodule prompting total thyroidectomy and genetic testing. The patient’s brother was found to be heterozygous for RET mutation (c.2617T>G;pSer891Ala). This resulted in screening of the other siblings including this patient, also found to be heterozygous for this mutation. Both parents were deceased, and their clinical history is not known. Only one of the remaining two siblings had genetic testing; one brother refused testing for the mutation and one sister was positive for the mutation but had no thyroid nodules on ultrasound. She underwent prophylactic thyroidectomy. Neither the patient, nor his siblings, have any progeny. The patient screened negative for primary hyperparathyroidism and pheochromocytoma. Calcitonin (739, normal </=14.3 pg/mL)and CEA levels (31.7, 0-3.0 ng/mL) were elevated. Thyroid ultrasound (US) showed two solid hypoechoic nodules with lobulated margins and internal coarse calcifications in the right and two in the left thyroid lobe; 1.5 cm and 1.2 cm in maximum diameter, and 1.2 cm and 3 mm in maximum diameter, respectively. Based on elevated calcitonin and CEA levels, known RET mutation and evidence for thyroid nodules, we recommended a total thyroidectomy and central neck dissection. Pathology revealed multifocal, bilateral medullary carcinoma (largest focus of 1.5 cm), with 4/4 lymph nodes positive for metastasis. This was classified as mpT1bN1aM0 (Stage III). Patient was started on levothyroxine with plans to repeat calcitonin and CEA levels and neck ultrasound, 3 months following surgery. CT chest, abdomen and pelvis did not reveal any distant metastasis. Conclusion: Inherited MTCs are rare. Early diagnoses by screening of at-risk family members in MEN2 kindreds is important because MTC can be life-threatening and can be cured and prevented by early thyroidectomy. While our suspicion for FMTC in this patient and his siblings is high, FMTC is now considered a variant of MEN2A and ongoing screening for pheochromocytoma and primary hyperparathyroidism is recommended.