Objective: Differences in iodine intake could account for the variable prevalences reported for somatic TSHR and Gs alpha mutations in TTNs. However, this question has never been setteled, since no study has yet determined the TSHR mutation prevalence in TTNs in regions with and without iodine deficiency in the same population. Therefore we studied the prevalence of somatic TSHR mutations in TTNs by investigating TTNs from patients who lived in endemic and nonendemic goiter regions in Turkey.
Methods: We screened 78 TTNs from 59 patients for somatic TSHR mutations. Exon 910 of the TSHR and 78 of the Gs alpha were screened by denaturating gradient gel electrophoresis (DGGE). A PCR-based clonality assay was used for the clonality analysis of the mutation positive and negative nodules. Local Ethical Committee approval has been obtained.
Results: TSHR mutations were identified in 56 (71.8%) of 78 TTNs. Gs alpha mutation was identified in only one case. Four new TSHR mutations were detected (A428V, A627V, I640K and I486N). The D727 polmorphism was identified in 11 (18.6%) patients. No significant differences for the frequency of the TSHR mutation in endemic(70%) and nonendemic (74%) goiter regions of Turkey were found (χ2: 0.751 P: 0.57). The frequency of non-random-X-chromosome inactivation was similar in endemic (85.7%) and non endemic goiter (75%) regions and in TSH-receptor mutation positive (69.5%) or negative(69.3%) hot nodules.
Conclusion: These findings suggest that TTNs in both areas predominantly arise from aberrant growth of a single cell. Moreover, our results suggest that neither the proportion of TSHR mutations nor the proportion of the monoclonal origin of TTNs is related to iodine supply in the diet. This would imply that iodine more likely plays a role in determining the number of events that lead to thyroid autonomy rather than deciding the molecular signature of TTNs.