Chronic Iodine Excess and Aging Synergistically Impact Thyrotropin Elevation: A Prospective 20-Year Follow-Up Study in China

Background: Chronic iodine excess is associated with increased serum thyrotropin (TSH) levels. We assessed the independent and interactive effects of iodine-excess transition outcomes and aging on TSH levels over 20-year follow-up. Methods: The original prospective cohort study started in 1999 and focused on three communities in North China ( n = 1176). Based on the iodine status transition over the 20-year period, the euthyroid participants were categorized into groups according to urinary iodine concentrations (UIC): continuous iodine sufficiency (UIC 100–299 μg/L) (SI–SI, n = 261), from iodine excess (UIC >299 μg/L) to iodine deficiency (UIC <100 μg/L) (EI–DI, n = 145), from iodine excess to iodine sufficiency (EI–SI, n = 530), and continuous iodine excess (EI–EI, n = 240), respectively. Results: During 1999–2004, the baseline median TSH levels were positively associated with the initial UIC levels. After 20 years, for participants with negative thyroid antibodies, the three iodine-excess groups all exhibited elevated median TSH levels (SI–SI 1.81 mU/L vs. EI–DI 2.19 mU/L vs. EI–SI 2.08 mU/L vs. EI–EI 2.01 mU/L), an increased prevalence of mild subclinical hypothyroidism (SCH) with TSH <10.0 mU/L (SI–SI 5.3% vs. EI–DI 11.2% vs. EI–SI 12.3% vs. EI–EI 9.4%) and reduced central thyroid hormone sensitivity compared with the SI–SI group ( p < 0.05). However, the EI–EI group had the lowest TSH rising degree (SI–SI 0.32 mU/L [24.57%] vs. EI–DI 0.47 mU/L [24.56%] vs. EI–SI 0.45 mU/L [37.52%] vs. EI–EI 0.21 mU/L [14.18%], p < 0.05). Repeated-measures analysis revealed that aging was primarily related to a stable increase in TSH. Iodine-excess transition outcomes were also associated. Furthermore, a significant interaction effect existed between aging and different iodine-excess transition outcomes, modulating the TSH rising degree. Alleviation of iodine excess promoted aging-related TSH elevation, whereas persistent iodine excess suppressed aging-related TSH elevation. However, among participants with positive thyroid antibodies, no significant interaction effect above was observed. By comparison, there was a greater prevalence of SCH, especially an obvious high prevalence of severe SCH under persistent iodine excess. Conclusions: Elevated TSH levels induced by chronic iodine excess cannot be downregulated by reducing iodine intake. In nonautoimmune contexts, an interaction effect between iodine status and aging synergistically modulates the TSH rising degree. Iodine excess contributes to mild SCH and is correlated with high baseline TSH levels.