Navigating the Complexities of Multiple Endocrine Neoplasia Type 2B: A Case Report

Introduction Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant disorder characterized by the development of malignancies in two or more endocrine glands [1]. Patients typically present with aggressive medullary thyroid carcinoma (MTC) and may develop pheochromocytoma (PHEO) and mucosal ganglioneuromas [2,3]. Case Presentation A 23-year-old male underwent a thyroidectomy and lymphadenectomy at age 16 due to MTC (pT3N1M0). Genetic testing identified a rearranged during transfection (RET) mutation c.[2753T>C] (p.Met918Thr), confirming MEN 2B. Tumor recurrences required further surgeries. Blood tests showed elevated metanephrine, chromogranin A, and calcitonin, prompting a CT scan, which revealed a 0.7 × 0.5 cm metastatic mass in the right lung with no abdominal metastases. Due to a progressive rise in metanephrine concentration (0.5 → 1.73 pg/mL, normal range 0 – 0.456 pg/mL), an MRI scan revealed a mass in the right adrenal gland. Metaiodobenzylguanidine scintigraphy showed no iodine accumulation, suggesting a poorly differentiated adrenal tumor. A multidisciplinary team opted for a right adrenalectomy. As surgical options for MTC had been exhausted and calcitonin levels continued to rise (> 500 ng/L, normal range 0.56 – 2.81 ng/L), the decision was made to initiate targeted therapy with vandetanib on January 20, 2024, to inhibit RET tyrosine kinase activity while deferring radiation therapy. Histopathology of the adrenal gland confirmed PHEO. Discussion MEN 2B results from RET proto-oncogene mutations, leading to MTC, PHEO, and intestinal ganglioneuromas, without parathyroid involvement. Genetic testing, the key diagnostic tool for MEN 2B, confirmed the mutation. A positive test in the patient's younger sister suggests a familial link, further supported by the father's early death from an undiagnosed thyroid disorder. The delay in initiating aggressive systemic treatment for MTC highlights the need for timely surgical intervention, such as thyroidectomy with lymphadenectomy, and systemic therapies like RET inhibitors [4]. Early diagnosis, treatment, and long-term monitoring are critical to improving outcomes [5]. Conclusions This case highlights the importance of early MEN 2B diagnosis to prevent MTC progression and the need for aggressive treatment at the time of diagnosis.