Mutations of GNAS and TSHR genes in subclinical toxic multinodular goiter

This study aimed to detect the mutations of the GNAS and TSHR genes in subclinical toxic multinodular goiter (sTMG) and to evaluate the relationship between these mutations and sTMG.

Forty-four patients with sTMG and 20 matched controls (multinodular goiter) were recruited into this study. All of the patients underwent subtotal thyroidectomy. Gene mutations were analyzed by direct DNA sequencing of the polymerase chain reaction-amplified part of exons.

In the sTMG group, 3 mutations of the GNAS gene were identified in 7 patients (15.9%), and 6 mutations of the TSHR gene were identified in 14 patients (31.8%). The mutation rate of the TSHR gene in patients with sTMG was significantly higher than that in the control group. Furthermore, in the sTMG group, statistical analysis indicated that mutations were significantly correlated with the serum level of thyroid-stimulating hormone for the TSHR gene, but no significant difference was found for the GNAS gene. Also, no significant difference was found in mutation positivity of the 2 genes between patients with nodules who were born before universal salt iodization and patients with nodules who were born afterward (p > 0.05).

The results indicate that a mutation of the TSHR gene may be related to sTMG. The serum thyroid-stimulating hormone level plays an important role in the mutagenesis.