Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI119687

Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor.

P Kopp, S Muirhead, N Jourdain, W X Gu, J L Jameson, and C Rodd

Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA. petekopp@merle.acsn.nwu.edu

Find articles by Kopp, P. in: JCI | PubMed | Google Scholar

Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA. petekopp@merle.acsn.nwu.edu

Find articles by Muirhead, S. in: JCI | PubMed | Google Scholar

Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA. petekopp@merle.acsn.nwu.edu

Find articles by Jourdain, N. in: JCI | PubMed | Google Scholar

Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA. petekopp@merle.acsn.nwu.edu

Find articles by Gu, W. in: JCI | PubMed | Google Scholar

Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA. petekopp@merle.acsn.nwu.edu

Find articles by Jameson, J. in: JCI | PubMed | Google Scholar

Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA. petekopp@merle.acsn.nwu.edu

Find articles by Rodd, C. in: JCI | PubMed | Google Scholar

Published September 15, 1997 - More info

Published in Volume 100, Issue 6 on September 15, 1997
J Clin Invest. 1997;100(6):1634–1639. https://doi.org/10.1172/JCI119687.
© 1997 The American Society for Clinical Investigation
Published September 15, 1997 - Version history
View PDF
Abstract

Activating somatic mutations in the thyrotropin (TSH) receptor have been identified as a cause of hyperfunctioning thyroid adenomas, and germline mutations have been found in familial nonautoimmune hyperthyroidism and sporadic congenital hyperthyroidism. All mutations reported to date have been located in the transmembrane domain. We now report an example of an activating mutation in the extracellular, TSH-binding domain, found in a male infant with congenital hyperthyroidism due to a toxic adenoma. The pregnancy was remarkable for fetal tachycardia. Scintigraphic studies demonstrated a large nodule in the right lobe, and a hemithyroidectomy was performed at the age of 2 yr. Direct sequencing of the TSH receptor gene revealed a mutation in one allele resulting in a substitution of serine281 by isoleucine (Ser281--> Ile) in the extracellular domain. The mutation was restricted to the adenomatous tissue. Expression of the Ser281--> Ile mutation in vitro revealed an increase in basal cAMP levels. Affinity for TSH was increased by the mutation. These findings demonstrate that activating mutations can also occur in the extracellular domain of the TSH receptor, and support a model in which the extracellular domain serves to restrain receptor function in the absence of TSH or antibody-induced conformational changes.

Version history
  • Version 1 (September 15, 1997): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts