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Abstract

Autoimmune thyroid disease (AITD) is a common disorder especially in women, and both genetic and environmental factors are involved in its pathogenesis. We wanted to gain more insight into the contribution of various environmental factors. Therefore, we started a large prospective cohort study in subjects at risk of developing AITD, for example healthy female relatives of AITD patients. Here we report on their baseline characteristics. Only first- or second-degree female relatives of patients with documented AITD were included. Smoking habits, oestrogen use, pregnancy history and iodine exposure were assessed by questionnaires, and correlated to the thyroid function and antibody status. Of 803 subjects, 440 came from families with more than one patient with documented AITD. Of these families, 33% had documented cases of both Graves' disease and Hashimoto's thyroiditis. Although the subjects were in self-proclaimed good health, 3.6% were found to have hypothyroidism (overt disease in 1.3%) and 1.9% had hyperthyroidism (overt disease in 0.4%). These patients were older than the euthyroid subjects and were mostly positive for thyroid peroxidase (TPO) antibodies. Oestrogen use was associated with a lower rate of hyperthyroidism [relative risk (RR) 0.169; 95% confidence interval (CI) 0.06-0.52], whereas having been pregnant was associated with a higher relative risk for hyperthyroidism (RR 6.88; 95% CI 1.50-30.96). Of the 759 euthyroid subjects, 24% had TPO antibodies. Smoking and oestrogen use were negatively correlated with the presence of TPO antibodies. In the euthyroid subjects, TPO antibody titre correlated positively with TSH levels (r = 0.386; P < 0.001). The high prevalence of evidence for autoimmune thyroiditis at baseline supports the importance of genetic factors in its pathogenesis. The co-occurrence of Hashimoto's thyroiditis and Graves' disease within one family suggests a common genetic basis for these diseases. Oestrogen use is associated with a lower risk, and pregnancy with a higher risk for developing hyperthyroidism. The positive correlation between TPO antibody titres and TSH levels in euthyroid subjects suggests that TPO antibodies are indeed a marker of future thyroid failure.

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Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)

J Hollowell (2002)

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Smoking and risk of Graves' disease.

W. Wiersinga, M Prummel (1993)

To assess if smoking is associated with Graves' disease and, if so, to ascertain whether this association persists when controlling for confounding factors. Consecutive entry case-control study with two age- and sex-matched control subjects from two different populations per case patient. University hospital. Five groups were studied: (1) Graves' ophthalmopathy and Graves' hyperthyroidism (n = 100; divided in four subgroups according to the severity of the eye disease); (2) Graves' hyperthyroidism without clinical eye involvement (n = 100); (3) sporadic nontoxic goiter (n = 100); (4) autoimmune hypothyroidism (n = 75); and (5) toxic nodular goiter (n = 75). The study comprised 200 subjects from a hospital-based population, and 200 from a population-based group served as control subjects. Smoking status was determined from a questionnaire at the time of onset of the disease to exclude any effect of the disease itself on smoking. Smoking greatly increased the risk for Graves' ophthalmopathy (odds ratio, 7.7; 95% confidence interval, 4.3 to 13.7), but patients with Graves' hyperthyroidism alone were also more often smokers than control subjects (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2). Smoking was not associated with the other thyroid diseases studied. Essentially similar results were obtained after adjustment for differences in education between case patients and control subjects. Among the patients with Graves' ophthalmopathy, smokers had more severe eye disease than nonsmokers, but no association was found between the number of cigarettes smoked per day or the duration of smoking and the severity of the ophthalmopathy. However, there was a significant increase in the odds ratios in patients with more severe eye disease. Smoking is associated with Graves' disease, and it especially increases the risk for the development of more severe ophthalmopathy. Thus, smoking appears to be one of the multiple factors inducing Graves' disease in genetically predisposed individuals.