{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:31:50Z","timestamp":1774686710508,"version":"3.50.1"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,4,17]],"date-time":"2007-04-17T00:00:00Z","timestamp":1176768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World j. surg."],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Since DNA tests have enabled reliable identification of asymptomatic RET (rearranged during transfection) gene carriers, myriads of publications have appeared on genotype\u2010phenotype relationships. A comprehensive appraisal of this body of evidence using evidence\u2010based methodology is pending.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was based on systematic evaluation of the literature using evidence\u2010based criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(1) There is a distinct age\u2010related progression of hereditary medullary thyroid carcinoma (MTC) in carriers of RET mutations (grade C). (2) Among the high\u2010risk RET mutations, those in codon 634 cause higher penetrance rates of the multiple endocrine neoplasia 2A phenotype (MTC, pheochromocytoma, and parathyroid hyperplasia\/adenoma) than mutations in codons 609, 611, 618, and 620, irrespective of the amino acid substituting for cysteine (grade C). (3) DNA\u2010based screening is superior to calcitonin\u2010based screening in asymptomatic RET carriers (grade C). (4) Using a worst\u2010case scenario, i.e., considering the earliest finding of MTC in asymptomatic RET carriers, pre\u2010emptive thyroidectomy should be performed before that time (grade C) to be truly prophylactic. Specifically, for carriers of highest\u2010risk mutations (codon 918): within the first year of life; for carriers of high\u2010risk mutations (codon 609, 611, 618, 620, 630, and 634): before the age of 5 years; and for carriers of least\u2010high risk mutations (codon 768, 790, 791, 804, and 891): before the age of 5\u201010 years. Strict adherence to these grade C recommendations can result in undertreatment of the former (codon 634) and overtreatment of the latter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These genotype\u2010phenotype correlations provide a solid foundation on which to base surgical concepts, leaving little room for randomized controlled clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00268-006-0769-y","type":"journal-article","created":{"date-parts":[[2007,4,23]],"date-time":"2007-04-23T15:08:48Z","timestamp":1177340928000},"page":"957-968","source":"Crossref","is-referenced-by-count":84,"title":["Genotype\u2010Phenotype Based Surgical Concept of Hereditary Medullary Thyroid Carcinoma"],"prefix":"10.1002","volume":"31","author":[{"given":"Andreas","family":"Machens","sequence":"first","affiliation":[{"name":"Department of General, Visceral and Vascular Surgery Martin\u2010Luther\u2010University Halle\u2010Wittenberg Ernst\u2010Grube\u2010Str. 40 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