Development of Thyroid Dysfunction and Autoantibodies in Graves' Multiplex Families: An Eight-Year Follow-Up Study in Chinese Han Pedigrees

Abstract

This 8-year follow-up study is aimed at determining the relapse and development of Graves' disease (GD) and the potential risk factors that could be associated with the development of thyroid dysfunction and autoantibodies in Chinese pedigrees. Fifty-four Chinese Han GD pedigrees (322 members) were recruited in 2000. Forty-five pedigrees (263 members) were followed up. Their clinical and laboratory characteristics and fasting urinary iodine were measured with the same method at the two time points. We found that the mean age for onset of GD in offspring was much younger than that of their parents (p=0.013). At baseline, the prevalence of hyperthyroidism, hypothyroidism, and subclinical hypothyroidism in first-degree relatives were 5.5%, 1.6%, and 1.1%, respectively. Individuals with thyroid dysfunction were positive for thyroid autoantibodies. The prevalence of positive thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), or TSH receptor antibody (TRAb) in the first-degree relatives with euthyroidism in these pedigrees was 18.6%, 17.4%, or 56.9%, respectively. At follow-up, individuals with positive TPOAb were at risk of developing thyroid dysfunction, whereas patients with positive TRAb had increased risk for relapse even after drug treatment. The percentage of nonsmokers with positive TPOAb and TgAb was significantly higher than that of smokers (p<0.05), but the levels of serum TRAb were significantly higher in smokers at follow-up than baseline (p<0.01). Genetic factors are crucial for the development of autoimmune thyroid disease (AITD), thyroid dysfunction, and the outcomes of Graves' patients following treatment with medicines. Although smoking was negatively associated with the presence of thyroid antibodies (TPOAb/TgAb), smoking may induce or aggravate GD.