Die Knotenstruma. Die molekulare Entstehung - Konsequenzen für die Therapie?

Zusammenfassung

Strumen und Schilddrüsenknoten sind oftmals Zufallsbefunde und treten in milden Jodmangelgebieten Deutschlands bei bis zu 15 % bzw. 30 % der Erwachsenen auf.Jodmangel ist der wichtigste exogene Faktor für die Entstehung von Strumen und Schilddrüsenknoten. Der regulatorische Effekt von Jod auf Schilddrüsenwachstum und -funktion wird durch Wachstumsfaktoren, insbesondere IGF1 und Jodlaktone vermittelt. Da der intrathyreoidale Jodgehalt in Deutschland stark reduziert ist, wird die Hemmung des Wachstums durch Jodlipide verringert. Für eine zusätzliche genetische Komponente in der Genese von Strumen sprechen insbesondere Familienstudien, die zeigten, dass die Strumaprävalenz bei Kindern steigt, wenn Mutter und/oder Vater betroffen sind. Auch Zwillingsstudien in Gebieten milden Jodmangels beschreiben ein im Vergleich zur restlichen Population gehäuftes Auftreten von Strumen bei Patienten, deren eineiiger oder zweieiiger Zwilling betroffen ist. Ganzgenomische Kopplungsanalysen in Familienstudien lieferten Hinweise für zwei Hauptloci, MNG-1 und Xp22, bei Patienten mit euthyreoter Struma. Kopplungen der euthyreoten Struma zu den Schilddrüsen-Kandidatengenen TG, TPO, NIS, PDS und zu dem TSH-Rezeptor waren nicht nachweisbar. Mutationen im TSH-Rezeptor und in der Gsα-Untereinheit können die cAMP-Kaskade aktivieren, ohne dass eine Stimulation durch TSH notwendig ist und führen für die betroffenen Zellen zu einem Wachstums- und Funktionsvorteil. Aus pathophysiologischen Überlegungen heraus sollte Jodid als Monotherapeutikum oder in Kombination mit Levothyroxin erste Wahl in der Behandlung benigner, euthyreoter Knotenstrumen sein. Dafür sprechen auch die Ergebnisse epidemiologischer Studien, die einen kausalen Zusammenhang zwischen mildem Jodmangel und der Prävalenz von Knotenstrumen beschrieben. Bei knotig umgewandeltem Schilddrüsengewebe ist aufgrund des erhöhten Rezidivrisikos eine subtotale oder nahezu totale Thyreoidektomie durch einen erfahrenen Chirurgen oder eine Radiojodtherapie indiziert.

Abstract

Up to 15 % of the adult German population display an enlarged thyroid gland and up to 30 % present thyroid nodules. Iodine deficiency is the most important factor in the etiology of nodular goiter. Insulin-like growth factor-I is overexpressed in thyroids in severely iodine deficient areas. There is evidence that iodolactones are mediators of thyroid hormone autoregulation. However familial and twin studies demonstrated a genetic component in the etiology of nodular goiter. Linkage analysis identified two chromosomal regions (MNG-1, Xp 22) in multinodular goiter. Other possible candidate genes or markers such as TG, TPO, NIS, PDS and TSH-R were not identified. Nodular goiter certainly comprises a number of genotypes. TSH receptor mutations result in activation of the cAMP cascade. Cells with a constitutively activated cAMP cascade have an increased growth advantage due to their TSH independent cAMP stimulation. Alimentary iodine supply should be the first choice in primary prevention of nodular thyroid disease in iodine deficient areas, because prevalence of nodular goiter is negative correlated with individual iodine status in epidemiological surveys. Surgical removal of nodular goiters should include nearly the hold thyroid tissue to avoid recurrent goiter.

Strumen - Schilddrüsenknoten - Jodmangel - Therapie

Goiter - thyroid nodules - iodine deficiency - therapy

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