Pheochromocytoma/Paraganglioma, Medullary Thyroid Carcinoma, and Hereditary Endocrine Neoplasia Syndromes

Endocrine neoplasms comprise a variety of benign and malignant tumors that arise from the endocrine glands or other neuroendocrine tissues, such as the paraganglia. Most childhood endocrine tumors, typified by papillary thyroid carcinoma, are sporadic and not attributable to an identifiable germline mutation, whereas others, epitomized by catecholamine-producing tumors and medullary thyroid carcinoma, are familial and occur within the context of a broader hereditary tumor syndrome. In familial endocrine neoplasms, the mode of inheritance is autosomal dominant and mutations are primarily inactivating mutations causing loss of function in a tumor suppressor gene. Advances in genetic testing and research have led to the ongoing discovery of novel tumor-susceptibility genes, in addition to a better understanding of the underlying pathophysiology of these unique disorders. Knowledge regarding genotype-phenotype relationships continues to evolve, as has clinical practice regarding the age of performing predictive genetic testing, screening for endocrine tumors in an asymptomatic carrier, and the timing of therapeutic intervention. Given the rapidly changing field, it is beneficial for patients with an endocrine tumor to be evaluated in programs with known multidisciplinary expertise. In addition, the results of genetic testing and formal genetic counseling should be fully incorporated into treatment planning and long-term follow-up. This chapter reviews the pathophysiology, diagnosis, and management of pediatric endocrine tumors and the most common genetic syndromes associated with their diagnosis.