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Vor 30\u00a0Jahren konnten die Keimbahnmutationen im <jats:italic>RET(REarranged-during-Transfection)-<\/jats:italic>Protoonkogen, einem Tumorsuppressorgen auf Chromosom 10q11.2, als Ursache der MEN2 identifiziert und 1993 und 1994 erstver\u00f6ffentlicht werden. Hieraus entwickelte sich das Konzept der prophylaktischen Thyreoidektomie f\u00fcr asymptomatische Genmutationstr\u00e4ger, das seither Therapiestandard ist. Klinisch-genetische Untersuchungen zeigten hinsichtlich der individuellen Genmutation eine Genotyp-Ph\u00e4notyp-Korrelation sowohl hinsichtlich der Penetranz und des Entstehungszeitraums des MTC und in geringerem Ausma\u00df auch hinsichtlich der anderen MEN2-Komponenten Ph\u00e4ochromozytom und prim\u00e4rer Hyperparathyreoidismus. Daraus konnte eine klinisch relevante Risikostratifizierung abgeleitet werden. Die allein genotypbasierte, aber nicht hinreichend genaue Altersempfehlung f\u00fcr den besten Zeitpunkt der prophylaktischen Thyreoidektomie wurde in der Folgezeit durch Kombination des <jats:italic>RET<\/jats:italic>-Genotyps mit dem Kalzitoninwert pr\u00e4zisiert, der mutations- und altersunabh\u00e4ngig erst bei \u00dcberschreiten des oberen Kalzitoninnormwertes das Risiko einer Lymphknotenmetastasierung anzeigt. Die routinem\u00e4\u00dfige Kalzitoninbestimmung bei Knotenstrumen, das Familienscreening bei MEN2-Indexpatienten und die karzinompr\u00e4ventive prophylaktische Thyreoidektomie bei normokalzitonin\u00e4mischen Genmutationstr\u00e4gern haben dazu gef\u00fchrt, dass heute, 30\u00a0Jahre nach der Erstbeschreibung der krankheitsverursachenden Genmutationen, das lebensbedrohende heredit\u00e4re MTC heilbar geworden ist: ein leuchtendes Beispiel f\u00fcr den Erfolg translational transnationaler medizinischer Forschung zum Wohl der Betroffenen.<\/jats:p>","DOI":"10.1007\/s00104-024-02105-x","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T21:02:19Z","timestamp":1716930139000},"page":"638-650","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["30\u00a0Jahre prophylaktische Thyreoidektomie beim heredit\u00e4ren medull\u00e4ren Schilddr\u00fcsenkarzinom","30\u00a0years of prophylactic thyroidectomy for hereditary medullary thyroid cancer"],"prefix":"10.1007","volume":"95","author":[{"given":"Henning","family":"Dralle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Machens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"2105_CR1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1093\/hmg\/2.7.851","volume":"2","author":"H Donis-Keller","year":"1993","unstructured":"Donis-Keller\u00a0H, Don\u00a0S, Chi\u00a0D et\u00a0al (1993) Mutations in the RET proto-oncogene are associated with MEN2A and FMTC. 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