Multiple Endocrine Neoplasia Type 2 (MEN2)

Multiple endocrine neoplasia type 2 (MEN2) is a rare genetic disorder characterized by the occurrence of tumors in multiple endocrine glands. The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is sufficient to cause the disorder.

Causes and Genetics

MEN2 is caused by mutations in the RET proto-oncogene, which provides instructions for making a protein that is involved in signaling within cells. This mutation leads to the production of an abnormal protein that can stimulate cell growth and division, resulting in tumor formation.

Types of MEN2

There are three subtypes of MEN2:

• MEN2A: This is the most common subtype, accounting for about 90% of cases. It is characterized by the presence of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism.
• MEN2B: This subtype accounts for about 5-10% of cases and is characterized by the presence of MTC, pheochromocytoma, and other features such as marfanoid habitus, mucosal neuromas, and intestinal ganglioneuromatosis.
• Familial Medullary Thyroid Carcinoma (FMTC): This subtype is characterized by the presence of MTC only, without other endocrine tumors.

Symptoms

The symptoms of MEN2 vary depending on the specific subtype and the organs affected. Common symptoms include:

• Neck mass or swelling due to thyroid tumor
• High blood pressure due to pheochromocytoma
• Kidney stones or abdominal pain due to hyperparathyroidism
• Gastrointestinal symptoms such as diarrhea, constipation, or abdominal pain due to intestinal ganglioneuromatosis

Diagnosis

Diagnosis of MEN2 is based on a combination of clinical evaluation, laboratory tests, and genetic testing. The following tests may be used:

• Genetic testing for RET mutations
• Calcitonin levels to diagnose MTC
• Catecholamine levels to diagnose pheochromocytoma
• Parathyroid hormone levels to diagnose hyperparathyroidism
• Imaging studies such as CT or MRI scans to evaluate tumor size and extent

Treatment

Treatment of MEN2 depends on the specific subtype and the organs affected. The following treatments may be used:

• Surgery to remove thyroid tumors, pheochromocytomas, or parathyroid glands
• Chemotherapy or targeted therapy to treat MTC or other tumors
• Medications to control high blood pressure or hyperparathyroidism
• Regular follow-up and screening to monitor for tumor development or recurrence

Prognosis

The prognosis of MEN2 varies depending on the specific subtype, the age at diagnosis, and the effectiveness of treatment. Early detection and treatment can significantly improve outcomes, while delayed diagnosis or inadequate treatment can lead to poor prognosis.