Multiple endocrine neoplasia, type 2 (MEN2) is caused by changes (called mutations or pathogenic variants) in the RET gene. Individuals with MEN2 are at an increased risk to develop medullary thyroid cancer, pheochromocytomas of the adrenal glands (rare tumor that can make your adrenal glands produce more hormone than they’re supposed to), and parathyroid gland adenomas (benign tumors). MEN2 can be broken down into three subtypes:
All three subtypes have a 95-100% chance to develop MTC. Individuals with MEN2A and MEN2B also have a 50% chance to develop pheochromocytoma, while people with MEN2A also have a 20-30% chance to develop parathyroid disease.
|Subtype||Medullary thyroid |
Pathogenic variants in RET are inherited in an autosomal dominant pattern, meaning that children of a mutation carrier each have a 50% risk to inherit the mutation and associated cancer risks. Notably, women and men both have the RET gene and have the same chances to inherit and pass down mutations in this gene. Therefore, both sides of the family are important when assessing inherited risk. However, the associated cancers and lifetime risks are different between men and women.
A diagnosis of MEN2 is made if your personal or family history meets established clinical criteria (based on medical history, physical examination, and family history) that has been evaluated by a provider who is familiar with MEN2. Some red flags in a family history that can increase the chance for MEN2 are:
This condition can also be diagnosed by identification of a pathogenic variant in the RET gene through genetic testing.
Genetic testing can be ordered with different approaches, depending on the history and available information:
Management for individuals with MEN2 is complex and largely individualized depending on the person’s medical and family history, as well as the specific gene change that they carry. Sometimes the specific pathogenic variant can tell us whether someone has MEN2A, MEN2B, or FMTC. The specific variant can also tell us how high someone’s risk may be to develop related health concerns, and what age to begin certain types of screening. There may also be specific medications that your doctor may have you avoid if you have a diagnosis of MEN2. Preventative surgery, lab testing, and imaging with ultrasound, MRI, or CT scan can be used to help keep individuals who have MEN2 healthy. It is important to work with your doctor to develop the screening plan that will work best for you.