Background: We aimed to assess the long-term effects of the transition in iodine status on the incidence of thyroid disorders over 20 years of follow-up. Methods: The original prospective cohort study, started in 1999 ( n = 3761), classified three regions in north China based on iodine status (insufficient iodine, more than adequate iodine, and excessive iodine, respectively) for 5 years. Subsequently, participants were followed for up to another 15 years to assess the long-term effects of shifts to adequate iodine on the incidence of thyroid disorders. Panshan transitioned from insufficient to adequate iodine, and Huanghua transitioned from excessive to more than adequate iodine. Both regions were compared with Zhangwu, in which iodine status changed from more than adequate to adequate iodine (from 214 to 167.2 μg/L). A cluster sampling method was used to select participants in the three regions. Participants completed questionnaires and underwent thyroid ultrasonography. Urinary iodine concentrations (UICs), serum thyroid hormone concentration, and thyroid antibodies were measured. Results: When the iodine status changed from insufficient to adequate (with the median UIC increasing from 88 to 141.9 μg/L), the incidence density of subclinical hyperthyroidism, positive thyroperoxidase antibody, positive thyroglobulin antibody (TgAb), and goiter decreased significantly ( p < 0.05 for all). Additionally, the cumulative incidence of subclinical hypothyroidism was significantly lower compared with the region where the iodine status changed from being more than adequate to adequate (1.9% vs. 6.0%, p < 0.001). When the iodine status changed from excessive to more than adequate (median UIC from 634 to 266.7 μg/L), a significant decrease in the incidence density of subclinical hyperthyroidism, positive thyroid antibodies, positive TgAb, and goiter ( p < 0.05 for all) were also found. However, an increase in thyroid nodule incidence density (17.26 vs. 28.25 per 1000 person-years, p < 0.001) was seen. Conclusions: The incidence of thyroid disorders (except for thyroid nodules) stabilized or decreased among adults in the three communities from year 5 to year 15 of follow-up. Appropriate iodine fortification is safe and effective over the long term. Restoring urinary iodine to appropriate levels reduces population risk for thyroid disorders.

Background: Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959–1961) in early life and thyroid function and disorders in adulthood. Methods: Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Results: Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood ( β = 0.024; p = 0.038), compared with the nonexposed participants. The association was significant among rural participants ( β = 0.039; p = 0.02) but not in urban participants ( β = 0.005; p = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules ( p > 0.05). Conclusions: Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary–thyroid axis.

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.