Phenotype-driven cascade screening in a Syrian family with clinically consistent multiple endocrine neoplasia type 2A

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant hereditary endocrine tumor syndrome classically associated with medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism. Early recognition is important because cascade screening may identify affected relatives before advanced disease develops. We report a Syrian family with a clinically MEN2A-consistent phenotype. The index patient, a 37-year-old male, presented with a large multinodular thyroid mass and was found to have markedly elevated plasma metanephrines, bilateral adrenal masses, and elevated serum calcitonin and carcinoembryonic antigen. He underwent bilateral adrenalectomy followed by total thyroidectomy with bilateral neck dissection. Histopathology confirmed bilateral pheochromocytoma and multifocal MTC with gross extrathyroidal extension and lateral cervical lymph-node metastasis. Phenotype-driven cascade screening identified a 39-year-old sister with elevated calcitonin, metanephrine, and normetanephrine levels, bilateral adrenal masses, bilateral pheochromocytoma, and MTC, representing a second first-degree relative with the MEN2A-defining combination of MTC and bilateral pheochromocytoma. A 26-year-old brother was found to have synchronous papillary thyroid carcinoma and oncocytic/Hürthle-cell carcinoma with negative calcitonin immunostaining. This family highlights the value of phenotype-driven cascade screening when rearranged during transfection (RET) proto-oncogene testing is unavailable and emphasizes the importance of precise pathological classification of nonmedullary thyroid tumors in individuals from MEN2A-consistent families.