Iodine deficiency is associated with increased thyroid hormone sensitivity in individuals with elevated TSH

Central sensitivity of thyroid hormone refers to the sensitivity of hypothalamic-pituitary-thyroid (HPT) axis to the change in circulating free thyroxine (fT4). A complex relationship exists between thyroxine levels and iodine nutritional status. To explore the relationship between thyroid hormone sensitivity and iodine nutritional status in elevated thyrotropin (TSH), we used national data to assess the relationship between thyroid hormone sensitivity and iodine nutritional status with contrasting demographic characteristics in China.

We enrolled 12,197 participants with TSH > 4.2 mIU/L from China. Serum and urine samples were collected, and we measured serum fT4, TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels and urinary iodine concentration (UIC). The thyroid hormone sensitivity indices were calculated based on fT4 and TSH. The thyroid feedback quantile-based index (TFQI) is a new index to reflect thyroid hormone sensitivity. Higher TFQI quartiles indicated lower thyroid hormone sensitivity.

The odds ratios (ORs) for the fourth versus first TFQI quartile were 0.84 (95% CI 0.72-0.99) for iodine deficiency, 1.24 (95% CI 1.05-1.47) for TPOAb+, and 0.44 (95% CI 0.40-0.50) for females. The OR of the fourth and first TFQI quartiles for age <30 years and >60 years was 2.09 (95% CI 1.82-2.41) and 1.19 (95% CI 1.05-1.36), respectively (P < 0.05). Other thyroid sensitivity indices also yielded similar results.

Thyroid hormone sensitivity and age have a U-shaped association in individuals with elevated TSH. Increased thyroid hormone sensitivity is associated with iodine deficiency and the female gender. Decreased thyroid hormone sensitivity is associated with TPOAb+. These findings are interesting and potentially useful for understanding the interaction between iodine nutrition and the hypothalamic-pituitary-thyroid axis.