Efficacy of iodine-131-metaiodobenzylguanidine therapy for multiple endocrine neoplasia type 2A-associated metastatic pheochromocytoma: case report and literature review

Abstract

Malignant transformation in multiple endocrine neoplasia type 2 (MEN2)-associated pheochromocytoma is rare, and there have been few reports of treatment with ¹³¹I-metaiodobenzylguanidine (MIBG) therapy. Here, we describe a 47-year-old woman diagnosed as having bilateral pheochromocytoma with medullary thyroid carcinoma. Genetic testing confirmed the MEN2A subtype with the pathogenic variant p.C634Y in the RET oncogene. She underwent total thyroidectomy due to medullary thyroid carcinoma with elevated calcitonin levels as high as 1,380 pg/mL, classified as pT2N0M0, stage I. Plasma noradrenaline levels were significantly elevated, and abdominal computed tomography showed bilateral tumors of up to 6 and 2 cm in the right and left adrenal glands, respectively. She underwent right adrenalectomy and left partial adrenalectomy. Pathological examination confirmed bilateral pheochromocytoma, with Ki-67 indices of 2% and 12% in the left and right adrenal tumors, respectively. Calcitonin and catecholamine levels decreased after surgery. Seven years later, elevated plasma-free normetanephrine levels along with multiple metastases in the liver, spine, and pelvis on MIBG scintigraphy were indicative of metastatic pheochromocytoma. She underwent ¹³¹I-MIBG therapy with a dose of 7.6 GBq. Despite no significant change in metastatic or left adrenal tumor size, normetanephrine levels decreased from 1,210 to 437 pg/mL, and the patient has remained stable for more than 2 years after treatment without tumor growth. The malignant potential of MEN2A-associated pheochromocytoma emphasizes the need for accurate informed consent, especially when performing partial adrenalectomy. While ¹³¹I-MIBG therapy appears promising, its efficacy requires further assessment due to the limited number of reported cases of MEN2A-associated metastatic pheochromocytoma.