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The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2: from the removal of target organs at the expense of greater operative morbidity to close biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands. The lead time provided by early identification of asymptomatic MEN2 carriers under biochemical surveillance delimits a \u2018window of opportunity\u2019, within which (i) pre-emptive total thyroidectomy alone is adequate, circumventing morbidity attendant to central node dissection; (ii) subtotal \u2018tissue-sparing\u2019 adrenalectomy is sufficient, trading the risk of steroid dependency for the risk of a second pheochromocytoma in the adrenal remnant and (iii) parathyroidectomy is limited to enlarged glands, trading the risk of postoperative hypoparathyroidism for the risk of leaving behind hyperactive parathyroid glands. Future research should delineate further the mutation-specific, age-dependent penetrance of pheochromocytoma and primary hyperparathyroidism to refine the risk-oriented approach to MEN2. The sweeping changes in the management of MEN2 since the new millenium hold the hope that death and major morbidity from this uncommon disease can be eliminated in our lifetime.<\/jats:p>","DOI":"10.1530\/erc-17-0202","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T20:30:18Z","timestamp":1504816218000},"page":"T41-T52","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":39,"title":["Advances in risk-oriented surgery for multiple endocrine neoplasia type 2"],"prefix":"10.1530","volume":"25","author":[{"given":"Andreas","family":"Machens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Dralle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2018011817200993000_25.2.T41.1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.141.12.1199"},{"key":"2018011817200993000_25.2.T41.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.3.770"},{"key":"2018011817200993000_25.2.T41.3","first-page":"2415","article-title":"RET mutations in exons 13 and 14 of FMTC patients","volume":"10","author":"Bolino","year":"1995","journal-title":"Oncogene"},{"key":"2018011817200993000_25.2.T41.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2003.08.005"},{"key":"2018011817200993000_25.2.T41.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-007-9402-y"},{"key":"2018011817200993000_25.2.T41.6","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3182a6f43a"},{"key":"2018011817200993000_25.2.T41.7","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1210\/jc.2014-4508","article-title":"Reference range of serum calcitonin in pediatric population","volume":"100","author":"Castagna","year":"2015","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"2018011817200993000_25.2.T41.8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70154-8"},{"key":"2018011817200993000_25.2.T41.9","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.7.851"},{"key":"2018011817200993000_25.2.T41.10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/978-3-642-84749-3_9","article-title":"Surgical management of MEN2","volume":"125","author":"Dralle","year":"1992","journal-title":"Recent Results in Cancer Research"},{"key":"2018011817200993000_25.2.T41.11","doi-asserted-by":"publisher","DOI":"10.1007\/s002689900463"},{"key":"2018011817200993000_25.2.T41.12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2046"},{"key":"2018011817200993000_25.2.T41.13","first-page":"509","article-title":"A novel point mutation in the tyrosine kinase domain of the RET proto-oncogene in sporadic medullary thyroid carcinoma and in a family with FMTC","volume":"10","author":"Eng","year":"1995","journal-title":"Oncogene"},{"key":"2018011817200993000_25.2.T41.14","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1996.03540190047028"},{"key":"2018011817200993000_25.2.T41.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.01.012"},{"key":"2018011817200993000_25.2.T41.16","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21385"},{"key":"2018011817200993000_25.2.T41.17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198802253180804"},{"key":"2018011817200993000_25.2.T41.18","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1056\/NEJM197811022991804","article-title":"Natural history of familial medullary thyroid carcinoma. 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