Multiple Endocrine Neoplasia Syndromes
Multiple endocrine neoplasia (MEN) syndromes are rare hereditary disorders of benign and malignant endocrine neoplasms. There are 2 syndromes, MEN 1 and MEN 2. Both are typically autosomal dominant, but sporadic cases exist. MEN 2 is further divided into types 2A, 2B (Figs 2-2, 2-3), and medullary thyroid cancer (MTC) alone.
The most common features of MEN 1 are parathyroid, enteropancreatic, and pituitary tumors. Hyperparathyroidism is the most common endocrine abnormality. Enteropancreatic tumors include gastrinomas, which cause increased gastric acid output (Zollinger-Ellison syndrome), and insulinomas, which cause fasting hypoglycemia. Pituitary adenomas can also be present; they are usually prolactinomas, but other types can occur. Carcinoid and adrenal tumors can develop as well.
MEN 2A and 2B are characterized by the presence of MTC, which occurs in 90%–100% of patients and is the main cause of morbidity. The lifetime incidence of pheochromocytoma is approximately 50%. Hyperparathyroidism is seen in approximately 20%–30% of patients with MEN 2A but is rarely seen in patients with MEN 2B.
MEN 2B is characterized by ganglioneuromas, which occur in 95% of patients. They can be present on the lips, eyelids, and tongue, giving these patients a characteristic phenotype that may be apparent at birth. Patients with MEN 2B may also have marfanoid features including pectus excavatum and scoliosis, but without lens subluxation and aortic disease. The eyelid margins may be nodular as a result of multiple small tumors (see Fig 2-2); subconjunctival neuromas have also been reported. Perhaps the most striking ophthalmic finding is the presence of prominent corneal nerves in a clear stroma (see Fig 2-3), a phenomenon reported in 100% of cases. Because MTC may not appear until the patient’s second or third decade, ophthalmic manifestations may be the initial sign of MEN 2B, making ophthalmologists potentially instrumental in the diagnosis of this disease.
The management of MEN depends on the nature of the tumors and usually involves medical treatment to control hormonal effects and/or surgical excision when possible. The genes that cause all types of MEN have been located, and genetic testing can identify patients at risk. Identification of affected family members is particularly important in MEN 2 because prophylactic thyroidectomy can decrease the risk of death from MTC. Screening for pheochromocytoma is also warranted in order to identify problems that could lead to the development of complications such as hypertension.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.