Endocrine Abstracts

MEN2A is an autosomal dominant inherited syndrome, caused by a gain of function germline mutation in the RET proto-oncogene, with multiglandular tumoral development. Although the presence of MTC is very high and 50% of patients present with pheochromocytoma, the penetrance of hyperparathyroidism is estimated to be between 9 and 34%. The clinical presentation of the syndrome varies widely even in members of the same family, because of the difference of gene penetration (1). In 5% of cases, hyperparathyroidism may be the first manifestation. We present a patient with MEN2A, yet to be confirmed as a family case. MT, 53 yo woman, presented in our clinic in 2017 for medical evaluation. She was known with pheochromocytoma diagnosed at the age of 31, Graves disease with multinodular goiter, and operated breast cancer at 48 yo. She had normal urinary and plasma MN and NMN values, normal calcium, phosphate and PTH levels, and high calcitonin value (81 pg/ml). In the presence of a high risk thyroid nodule on ultrasound, total thyroidectomy was performed and MTC was confirmed. Recently, genetically testing revealed the presence of RET 11 Cys634Trp mutation and MEN2A was confirmed. Her sister, BC 49 yo, known with multiple melanomas, was subsequently evaluated and primary hyperparathyroidism due to parathyroid adenoma was diagnosed in the presence of repeated high calcium (10.7/10.61/10.8 mg/dl), high normal PTH (62 pg/ml) and normal 25-OH-vitamin D levels. MTC and pheocromocytoma were excluded and genetic testing result is in pending. What is the correct diagnosis for the second case? Does this patient with a solitary parathyroid adenoma have MEN2A syndrome or is it just a sporadic disease, in a family with different associated malignancies (breast cancer, malignant melanomas), where the RET mutation was confirmed in her sister?