Multiple endocrine neoplasia syndromes

Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands within a single patient. Five major forms of MEN are recognized and referred to as MEN types 1-5, and each form is characterized by the development of tumors within specific endocrine tissues. Each form of MEN is typically inherited as an autosomal-dominant syndrome but may occur sporadically; that is, without a family history, although this distinction between sporadic and familial cases may sometimes be challenging. In addition to the MEN syndromes, a number of additional monogenic disorders are characterized by endocrine neoplasia along with tumors affecting nonendocrine tissues. These multiple endocrine and other organ neoplasia syndromes (MEONS), which include the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, Von Hippel-Lindau (VHL) disease, Carney Complex (CNC), Neurofibromatosis type 1 (NF1), Cowden syndrome (CWD), and McCune-Albright syndrome (MAS), are reviewed in Chapter 43. Each of the MEN syndromes (MEN1-5) may be associated with a range of skeletal manifestations, which typically relate to complications of the respective endocrine tumors (e.g., osteoporosis related to primary hyperparathyroidism, skeletal metastases related to malignant endocrine and neuroendocrine tumors). This chapter reviews each of the MEN syndromes, highlighting the clinical manifestations and their relevance to skeletal disease, as well as providing a molecular overview of the respective monogenic disorder and its relevance to bone biology.