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A Population-Based Twin Case-Control Study

Thomas Heiberg Brix, MD; Pia Skov Hansen, MD; Kirsten Ohm Kyvik, MD, PhD; Laszlo Hegedüs, MD

Arch Intern Med. 2000;160:661-666.

Background  The effects of cigarette smoking on the thyroid gland have been studied for years. However, the effect of smoking on thyroid function and size is still controversial.

Objective  To determine the impact of cigarette smoking on the development of clinically overt thyroid disease.

Methods  Matched case-control study of 132 same-sex twin pairs (264 individuals) discordant for clinically overt thyroid disease, ascertained from a population-based nationwide twin register. Information on thyroid disease and smoking habits was gathered by questionnaire, and the patients' endocrinologist or general practitioner verified the diagnosis.

Results  Overall, smoking was associated with an increased risk of developing clinically overt thyroid disease (odds ratio, 3.0; 95% confidence interval, 1.4-6.6; P=.003). This association remained statistically significant in monozygotic and dizygotic disease-discordant pairs. The effect of smoking was more pronounced in monozygotic vs dizygotic pairs (odds ratio, 5.0 vs 2.5; P=.04 for both). Essentially similar results were obtained after subdividing the twin pairs into groups discordant for clinically overt autoimmune (49 pairs) and nonautoimmune (83 pairs) thyroid disease. Among twin pairs concordant for smoking, probands with clinically overt autoimmune thyroid disease smoked significantly more than did their healthy co-twins (17 pairs; P=.03), whereas no difference was found between probands with nonautoimmune thyroid disease and their healthy co-twins (34 pairs; P=.20).

Conclusions  Smoking is associated with an increased risk of developing clinically overt thyroid disease. Furthermore, our data suggest that cumulative cigarette consumption is a risk factor, most pronounced in autoimmune thyroid disease.

From the Department of Endocrinology, Odense University Hospital (Drs Brix, Hansen, and Hegedüs); and Danish Twin Register, Odense University (Drs Brix and Kyvik), Odense, Denmark.

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