Evidence for a more pronounced effect of genetic predisposition than environmental factors on goitrogenesis by a case control study in an area with low normal iodine supply.

Family and twin studies suggest a genetic predisposition for euthyroid goiters. However, iodine deficiency and smoking are important exogenous factors for goiter development. We investigated goiter predisposition by a matched case control study in a region with recently documented low normal iodine supply. A sum of 376 patients were included in the study. We matched 188 patients with euthyroid/subclinically hyperthyroid goiter (TSH 4.20-0.05 mU/l) with 188 euthyroid controls without thyroid enlargement for age and gender. Thyroid ultrasound was performed in all patients, whereby 50.5% of patients with goiters showed a positive family history for goiter. In contrast, only 25% of control patients had a positive family history (p<0.001; OR=3.1). Patients with goiters had a significantly higher proportion of parents (p<0.001; OR=3.6) or siblings (p=0.004; OR=2.5) with goiters. Children of parents with goiters showed a 2.7-fold increased risk for goiter development (goiter prevalence 73.3%). Patients with a positive goiter family history had a 4.1-fold increased goiter risk (p<0.001). The contribution of smoking, obesity, and pregnancies to goiter development was less important than the genetic predisposition (OR=1.7; p=0.06; OR=1.67; p=0.13; OR=0.8; p=0.56). In a region with low normal iodine supply, the significantly higher rate of positive family histories in patients with goiters as compared to the matched controls as well as the increased goiter prevalence in children of parents with goiters indicate the importance of genetic factors in goiter development.