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CLINICAL STUDY |
mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey
1 Section of Endocrinology and Metabolism and 2 Departments of General Surgery and 3 Pathology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, 34865 Istanbul, Turkey, 4 Department of Medical Biology, Marmara University Medical School, 34668 Istanbul, Turkey, and 5 Interdisciplinary Center of Clinical Research and 6 Department of Internal Medicine III, University of Leipzig, D-04103 Leipzig, Germany
(Correspondence should be addressed to R Paschke; Email: pasr{at}medizin.uni-leipzig.de)
Objective: Differences in iodine intake could account for the variable prevalences reported for somatic TSH receptor (TSHR) mutations in toxic thyroid nodules (TTNs). However, this question has not been settled, since no study has yet determined the TSHR mutation prevalence in regions with different iodine supplies in the same population using the same methodology. Therefore, we studied the prevalence of somatic TSHR mutations in TTNs from patients living in iodine-deficient or -sufficient regions in Turkey.
Design and methods: We screened 74 TTNs for somatic TSHR mutations. Exons 9 and 10 of the TSHR and 7 and 8 of the Gs
were screened by denaturing gradient gel electrophoresis. Determination of X-chromosome inactivation was used for clonality analysis.
Results: TSHR mutations were identified in 52 (70.2%) of 74 TTNs. A Gs
mutation was identified in one TTN. Three new TSHR mutations were detected (A627V, I640K, I486N). No significant difference between frequencies of TSHR mutations in iodine deficient/sufficient regions was found. The frequency of non-random X-chromosome inactivation was similar in iodine-sufficient or -deficient regions and in TSHR mutation positive or negative hot nodules.
Conclusions: These findings suggest that TTNs in iodine deficient/sufficient areas predominantly arise from aberrant growth of a single cell. Our results suggest that neither the prevalence of TSHR mutations nor that of monoclonal TTNs is related to iodine supply.
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