Langenbeck's Archives of Surgery

, Volume 385, Issue 6, pp 390–392 | Cite as

Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood

  • Heike Biebermann
  • Torsten Schöneberg
  • Heiko Krude
  • Thomas Gudermann
  • Annette Grüters
Original Article

Abstract.

Background: The glycoprotein hormone TSH (thyroid-stimulating hormone) and its receptor, the TSH-receptor (TSHR), play a crucial role in thyroid growth and function. Constitutively activating germline mutations within the TSHR gene were identified in patients with sporadic or familial non-autoimmune hyperthyroidism. Inheritance of these mutations is autosomal dominant. Patients and methods: We investigated two patients with neonatal onset of non-autoimmune hyperthyroidism and two families in whom the child and one parent are affected. Results: Hyperthyroidism was difficult to treat in all of these patients and was complicated by premature craniosynostosis. Sequencing of all exons of the TSHR gene in one family with hyperthyroidism revealed a mutation in exon 10 (T632I), which was first identified in toxic adenomas and found to constitutively activate the TSHR. In the other family, we identified a new mutation in the first membrane spanning segment (G431S). In both patients with sporadic hyperthyroidism, a heterozygous mutation in exon 9 (S281N) was detected. The functional characterization of S281N and G431S demonstrated that both mutants were constitutively active. Therefore, these mutations are the molecular cause of non-autoimmune hyperthyroidism in the patients. Conclusions: For patients suffering from non-autoimmune hyperthyroidism, screening for mutations and their functional characterization is recommended. In case of an ineffective hyperthyroidism treatment, thyroidectomy should be performed to prevent lengthy anti-thyroid drug treatment and complications like premature craniosynostosis.

Non-autoimmune hyperthyroidism TSHR Mutation Constitutive activity 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Heike Biebermann
    • 1
  • Torsten Schöneberg
    • 2
  • Heiko Krude
    • 1
  • Thomas Gudermann
    • 2
  • Annette Grüters
    • 1
  1. 1.Klinik und Poliklinik für Kinderheilkunde, Virchow-Klinikum, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyGermany
  2. 2.Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Thielallee 69–73, 14195 Berlin, GermanyGermany

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