Genetic and environmental causes of individual differences in thyroid size:: A study of healthy Danish twins

Factors such as iodine intake, serum TSH concentration, gender, age, body mass index, parity, and cigarette smoking are thought to influence thyroid size. The purpose of our study was to determine the relative roles of these environmental and physiological factors compared with genetic factors in euthyroid subjects with a clinically normal thyroid gland. A representative sample of self-reported healthy twin pairs was identified through the Danish Twin Registry. A total of 520 individuals divided into 104 monozygotic (MZ), 107 dizygotic same sex (DZ), and 49 opposite sex twin pairs were investigated. After adjustment for age, gender, and other covariates, intraclass correlations were calculated. To elucidate the relative importance of genetic and environmental factors to the variation of ultrasonically determined thyroid volume, quantitative genetic modeling was used. Regression analysis suggested that serum TSH, serum free T-4, gender, age, smoking, and body mass index each played a small, but significant, role for variation in thyroid volume. The intraclass correlations for thyroid volume were consistently higher for MZ than for DZ twin pairs (r(MZ) = 0.71; r(DZ) = 0.18; P < 0.001). Using quantitative genetic modeling, it was calculated that genetic factors (with 95% confidence intervals) accounted for 71% (61-78%) of the individual differences in thyroid volume. Genetic influences are important in the regulation of normal thyroid size. This fits the observation that goiter may be seen also in the absence of evident environmental goitrogens such as iodine deficiency and that not all individuals develop goiter even in iodine-deficient areas.