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Genetic and Environmental Causes of Individual Differences in Thyroid Size: A Study of Healthy Danish Twins

Department of Endocrinology M, Odense University Hospital (P.S.H., T.H.B., F.N.B., S.J.B., L.H.), DK-5000 Odense C, Denmark; and Danish Twin Registry, Department of Epidemiology, Institute of Public Health, University of Southern Denmark (P.S.H., K.O.K.), Odense, Denmark

Address all correspondence and requests for reprints to: Dr. Pia Skov Hansen, Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Sdr. Boulevard 23A, DK-5000 Odense C, Denmark. E-mail: piaskovhansen{at}dadlnet.dk.

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 T₄, 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.

This work was supported by grants from the Foundation of 17-12-1981, the Agnes and Knut Mørk Foundation, the Novo Nordisk Foundation, the Foundation of Medical Research in the County of Funen, Else Poulsens Mindelegat, the Foundation of Direktør Jacob Madsen and Hustru Olga Madsen, the Foundation of Johan Boserup and Lise Boserup, the A. P. Møller and Hustru Chastine McKinney Møllers Foundation, the A. P. Møller Relief Foundation, and the Clinical Research Institute, Odense University.

Abbreviations: BMI, Body mass index; CV, coefficient(s) of variation; DZ, dizygotic; MZ, monozygotic; OS, opposite sex; Tgab, thyroglobulin antibody; TPOab, thyroid peroxidase antibody.

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