What are the characteristics of Multiple Endocrine Neoplasia type 2 (MEN 2)?

From the Guidelines

Multiple Endocrine Neoplasia type 2 (MEN 2) management requires early genetic testing for RET proto-oncogene mutations, followed by prophylactic thyroidectomy for those who test positive, with the timing of thyroidectomy depending on the specific mutation, as outlined in the most recent guidelines 1. The syndrome is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism, with a prevalence estimated at 1:35,000 to 1:40,000 1. Key considerations in managing MEN 2 include:

• Genetic testing for RET proto-oncogene mutations to identify individuals at risk
• Prophylactic thyroidectomy for those who test positive, with the timing based on the specific mutation
• Screening for pheochromocytoma starting by age 8-10 with annual plasma metanephrines or 24-hour urinary catecholamines
• Hyperparathyroidism screening starting by age 20 with annual serum calcium and PTH measurements
• Regular lifelong follow-up after thyroidectomy, including calcitonin monitoring to detect recurrence The most recent study 1 provides the basis for these recommendations, emphasizing the importance of early genetic testing and tailored management based on the specific RET mutation. It's also important to note that MEN 2 follows an autosomal dominant inheritance pattern with nearly 100% penetrance for MTC, making family screening crucial 1. In terms of specific mutations, MEN 2B is characterized by a 100% risk of developing MTC, often presenting in infancy, and a 50% risk for pheochromocytoma, with no risk of hyperparathyroidism 1. In contrast, MEN 2A has a lower risk of MTC and pheochromocytoma, but may also include hyperparathyroidism 1. Overall, the management of MEN 2 should prioritize early genetic testing, prophylactic thyroidectomy, and regular screening for associated tumors, as outlined in the most recent guidelines 1.

From the Research

Definition and Causes of MEN 2

• Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer syndrome characterized by the presence of medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism 2, 3, 4, 5, 6.
• The disease is caused by germline mutations of the RET proto-oncogene, which leads to a gain-of-function mutation 2, 3, 4, 5, 6.

Subtypes of MEN 2

• There are two main subtypes of MEN 2: MEN 2A and MEN 2B 2, 3, 4, 5, 6.
• MEN 2A is associated with MTC, pheochromocytoma, primary hyperparathyroidism, cutaneous lichen amyloidosis, and Hirschsprung's disease 4.
• MEN 2B is associated with MTC, pheochromocytoma, ganglioneuromatosis of the aerodigestive tract, musculoskeletal and ophthalmologic abnormalities 4.
• Familial medullary thyroid carcinoma (FMTC) is considered a phenotypic variant of MEN 2A with decreased penetrance for pheochromocytoma and primary hyperparathyroidism 6.

Diagnosis and Management

• Early identification of patients with hereditary MTC has improved treatment outcomes 3.
• Genetic screening can diagnose MTC at preclinical disease states, resulting in a high cure rate and better prognosis 3.
• The management of patients with MEN 2 depends on an understanding of the variable behavior of disease expression in patients with a specific RET mutation 5.
• Information gained from molecular testing, biochemical analysis, and clinical evaluation is important in providing effective management of patients with either early or advanced-stage MTC 5.

Treatment Options

• Treatment includes early thyroidectomy, with recommendations on the timing and extent of surgery based on the RET mutation risk categories 3.
• Molecular targeted therapeutics have been shown to be effective in the treatment of patients with locally advanced or metastatic MTC 5.
• Registry-based follow-up should be mandatory, including documentation of short- and long-term outcomes to provide valid data for future counseling of patients with MEN 2 2.