Lack of Mutations in the TSHr and Gsα Genes in TSHr Antibody Negative Graves' Disease

Abstract

The aim of this study was to investigate whether TSHr antibody negative Graves' disease is associated with somatic mutations in the TSHr or Gsα genes and whether histopathologically defined thyroid lesions, i.e., hyperfunctioning adenoma, non-functioning follicular adenomas, or nodules in toxic and non-toxic multinodular goiters are associated with such mutations. No mutations but three germ-line polymorphisms were found in patients with TSHr antibody negative Graves' disease. The three polymorphisms are expected to have no or only minor effects on the signaling properties, and is not associated with altered antigenecity imposed by such mutations. Two heterozygous somatic TSHr mutations were found in two hyperfunctioning adenomas and in two toxic multinodular goiters. The lack of TSHr and Gsα mutations in TSHr antibody negative Graves' disease patients indicates that such mutations are neither primary nor secondary events in this disease. The results also confirm that somatic gain-of-function TSHr mutations are present in hyperfunctioning follicular adenomas and goiters, but not in non-functioning thyroid lesions.

Key words

Thyroid function - thyroid stimulating hormone (TSH) - thyroid-stimulating antibody - thyroid stimulating hormone receptor (TSHr) - thyroxine (T4)

References

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