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Angewandte Nuklearmedizin 2023; 46(03): 241-246
DOI: 10.1055/a-2030-6731
Wissen 2.0 - Schilddrüse und mehr
Übersicht

Medulläres Schilddrüsenkarzinom

Medullary thyroid cancer
Matthias Kroiß
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, München
2   Schwerpunkt Endokrinologie/Diabetologie, Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Würzburg
,
Viktoria Florentine Köhler
3   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, München
4   Schwerpunkte Diabetologie/Endokrinologie, Medizinische Klinik I, Johann-Wolfgang-Goethe-Universität, Frankfurt
,
Christine Spitzweg
5   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, München
6   Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic Rochester, Rochester, USA
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Zusammenfassung

Diagnose und Prognose Calcitonin ist ein sensitiver und spezifischer Tumormarker zur Früherkennung und Verlaufskontrolle des MTC. Daneben kommt dem Ultraschall der Schilddrüse eine entscheidende Rolle zu.

Rolle des RET-Proto-Onkogens Das medulläre Schilddrüsenkarzinom (MTC) nimmt seinen Ursprung aus den parafollikulären calcitoninproduzierenden C-Zellen. Es macht nur ca. 3–8% aller Schilddrüsenkarzinome aus. Aktivierende Mutationen im RET (rearranged during transfection)-Gen liegen bei etwa 25% der Patienten in der Keimbahn vor, werden aber auch beim sporadischen MTC als somatische Mutationen in ca. 60% der Fälle beobachtet. Bei metastasierter Erkrankung findet sich in 90% eine RET-Mutation. RET-Mutationen gelten als Treibermutationen und schließen weitere Treibermutationen weitestgehend aus. Seltener sind somatische Mutationen der RAS-Gene.

Chirurgische Therapie Die chirurgische Resektion ist bis heute der einzige kurative Therapieansatz. Entscheidend für eine frühzeitige Diagnosestellung ist die Bestimmung des Serum-Calcitonins bei Nachweis von Schilddrüsenknoten. Die chirurgische Therapie steht auch bei der Behandlung lokoregionärer Rezidive oder lokal angehbarer Metastasen im Zentrum.

Systemtherapie Bei irresektabel fortgeschrittener und progredienter Erkrankung mit signifikanter Tumorlast kann eine systemische Therapie erforderlich werden. Neuerdings ist die Kenntnis einer RET-Mutation im Tumorgewebe therapeutisch relevant, da mit dem selektiven RET-Inhibitor Selpercatinib eine neue, effektive und gut verträgliche Systemtherapien zur Verfügung steht. Dieser ist inzwischen wie bisher nur die Multityrosinkinaseinhibitoren Cabozantinib und Vandetanib als Erstlinientherapie des fortgeschrittenen MTC zugelassen. Vandetanib darf ebenfalls nur noch bei Patienten mit RET-Mutation angewendet werden.

Abstract

Diagnosis and prognosis Calcitonin is a sensitive and specific tumour marker for early detection and follow-up of MTC. In addition, the ultrasound of the thyroid gland plays a decisive role.

Role of the RET proto-oncogene Medullary thyroid carcinoma (MTC) originates from parafollicular calcitonin-producing C cells. It accounts for only about 3–8% of all thyroid carcinomas. Activating mutations in the RET (rearranged during transfection) gene are present in the germline in about 25% of patients, but are also observed in sporadic MTC as somatic mutations in about 60% of cases. In metastatic disease, a RET mutation is found in 90% of cases. RET mutations are considered driver mutations and largely exclude further driver mutations. Somatic mutations of the RAS genes are rarer.

Surgical therapy Surgical resection is still the only curative therapeutic approach. The measurement of serum calcitonin is crucial for an early diagnosis if thyroid nodules are detected. Surgical therapy is also a cornerstone of treatment in locoregional recurrences or locally approachable metastases.

Systemic therapy Systemic therapy may be required for irresectably advanced and progressive disease with significant tumour burden. Recently, the detection of a RET mutation in the tumour tissue has become therapeutically relevant, since a new, effective, and well-tolerated system therapy is available with the selective RET inhibitor selpercatinib. Like the multityrosine kinase inhibitors cabozantinib and vandetanib, it is now approved as a first-line therapy for advanced MTC. Vandetanib may also only be used in patients with RET mutations.

Schlüsselwörter

Medulläres Schilddrüsenkarzinom - MTC - Calcitonin - RET-Mutation - Selpercatinib

Keywords

Medullary thyroid cancer - MTC - calcitonin - RET mutation - Selpercatinib


Publication History

Article published online:
28 August 2023

© 2023. Thieme. All rights reserved.

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