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Wachstumshormoninsensitivität und schwerer primärer Mangel an insulinähnlichem Wachstumsfaktor-1

Behandlung im Kindesalter

Growth hormone insensitivity and severe primary deficiency of insulin-like growth factor-1

Treatment in childhood

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Zusammenfassung

Wachstumshormon (WH) und der insulinähnliche Wachstumsfaktor-1 („insulin-like growth factor-1“, IGF-1) spielen zentrale Rollen bei der Vermittlung von somatischem Körperwachstum. Störungen in der WH-stimulierten Signalkette sind ursächlich für seltene Formen der WH-Resistenz, die meist zu einer ausgeprägten Wachstumsstörung mit erniedrigter IGF-1-Konzentration führen. Da der genetische Hintergrund nur für einen Bruchteil der Störungen bekannt ist, wurde der Terminus „schwerer primärer IGF-1-Mangel („severe primary IGF-1 deficiency“, SPIGFD)“ eingeführt. Seit 2007 besteht eine Zulassung für rekombinantes IGF-1 (rIGF-1) zur Therapie des SPIGFD. Das rIGF-1 führte in Studien zu einer Verbesserung der Erwachsenenlänge von durchschnittlich 13 cm, aber nicht zu einem Größenzuwachs in dem Maß, wie er im Rahmen des frühzeitigen Ersatzes von WH bei Vorliegen eines WH-Mangels beobachtet wird. Wichtige Nebenwirkungen der Therapie mit rIGF-1 sind Hypoglykämien und die Proliferation von lymphatischem Gewebe. Die Erwachsenengröße bleibt trotz Therapie häufig unterhalb des Normalbereichs für Gesunde. Aufgrund ihrer Komplexität sollte die Therapie mit rIGF-1 in Zentren mit entsprechender Erfahrung erfolgen.

Abstract

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) play a fundamental role in somatic growth. Defects in the GH-stimulated signalling cascade underlie rare forms of GH resistance, which typically lead to severe growth impairment with reduced serum IGF-1. For a large proportion of patients the genetic background remains unclear; therefore the term severe primary IGF-1 deficiency (SPIGFD) was introduced. Since 2007, recombinant IGF-1 (rIGF-1) has been approved for the treatment of SPIGFD. Treatment with rIGF-1 led to an increase in final body height of approximately 13 cm in several studies but is not comparable to the increase in final height that is typically seen in GH-deficient children after GH substitution. Important side effects of rIGF-1 are hypoglycemia and the proliferation of lymphatic tissue. Adult height frequently remains below the normal range. Due to the complexities in the management of these rare diseases, treatment with rIGF-1 should be restricted to experienced pediatric endocrinologists.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. Prof. Woelfle ist Mitglied im wissenschaftlichen Beirat der Fa. Ipsen, einem Hersteller von IGF-1. Er erhielt Vortragshonorare von Ipsen, Novo Nordisk, Merck Serono. Er erhielt finanzielle Studienunterstützung von Pfizer und Ipsen. Der Beitrag enthält keine Studien an Menschen oder Tieren.

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  1. Pädiatrische Endokrinologie und Diabetologie, Universitäts-Kinderklinik Bonn, Adenauerallee 119, 53113, Bonn, Deutschland

    J. Woelfle

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Correspondence to J. Woelfle.

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Woelfle, J. Wachstumshormoninsensitivität und schwerer primärer Mangel an insulinähnlichem Wachstumsfaktor-1. Monatsschr Kinderheilkd 162, 309–314 (2014). https://doi.org/10.1007/s00112-013-3045-x

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  • DOI: https://doi.org/10.1007/s00112-013-3045-x

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