Clonal origin of toxic thyroid nodules with constitutively activating thyrotropin receptor mutations

The Journal of Clinical Endocrinology and Metabolism
K KrohnR Paschke

Abstract

Constitutively activating TSH receptor mutations have recently been detected in toxic nodules. In vitro studies suggest that mutated receptor signaling constitutively elevates cAMP, which causes hyperfunction and proliferation of thyrocytes. Therefore, toxic nodules with constitutively activating somatic TSH receptor mutations should result from clonal expansion of a single mutated cell. To test this hypothesis, we studied the clonal origin of 27 toxic nodules. In 13 of 27 nodules, a somatic mutation in the TSH receptor was identified. A PCR-based clonality assay that analyzes X-chromosome inactivation was used. The assay amplifies a polymorphism located in the androgen receptor gene. Of 27 toxic nodules studied, 23 (85%) were informative for the polymorphism. In the group that contains a somatic mutation in the TSH receptor, 10 of 11 cases showed nonrandom X inactivation, indicating clonal expansion. In only one toxic nodule with a TSH receptor mutation was random X inactivation detected. In the group without detectable mutations in exons 9 and 10 of the TSH receptor and exons 7-10 of the Gs alpha protein, only 6 of 12 toxic nodules show nonrandom X-chromosome inactivation. Therefore, the majority of toxic nodules with constit...Continue Reading

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Citations

May 27, 2008·Endocrinology and Metabolism Clinics of North America·Manuel Sobrinho-SimõesPaula Soares
Jun 13, 2008·Endocrine Pathology·Stefano Serra, Sylvia L Asa
Mar 1, 2008·Endocrinología y nutrición : órgano de la Sociedad Española de Endocrinología y Nutrición·Joaquín Lado Abeal, Lourdes Domínguez Gerpe

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