Archive | 2021
Syndromic Medullary Thyroid Cancer: MEN 2A and MEN 2B
Abstract
Abstract Since the advent of RET gene analysis in 1993, tremendous progress has been made in our understanding of the development of multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited endocrine syndrome. MEN 2 is subdivided into two clinical entities, both of which include distinct components that arise in an age-dependent manner and may not be present at the same time: MEN 2A, comprising medullary thyroid cancer, pheochromocytoma, and pseudonodular parathyroid hyperplasia, and MEN 2B, encompassing medullary thyroid cancer, pheochromocytoma, and various oral, ocular, intestinal, and “marfanoid” musculoskeletal manifestations. Deeper insight into the natural history of the disease has given rise to a paradigm shift in the operative management of MEN 2—from removal of target organs at the cost of greater morbidity to biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands. The lead time afforded by early detection of asymptomatic MEN 2 carriers under biochemical monitoring defines a “window of opportunity” within which (1) mere total thyroidectomy is sufficient, avoiding morbidity inherent in central lymph node dissection; (2) subtotal “tissue-sparing” adrenalectomy is a viable approach in view of the well-manageable risk of secondary pheochromocytoma; and (3) parathyroidectomy can be restricted to enlarged glands considering the low risk of recurrent hyperparathyroidism in MEN 2A. The impressive advances in the management of MEN 2 accrued in the genomic era raise hopes that death and major morbidity from MEN 2 can be abolished in our lifetime.