Behavior of serum thyroglobulin in relation to thyroid function under low-thyrotropin conditions in general practice

Serum thyroglobulin (Tg) and thyroid hormones are essential biomarkers in the diagnosis and management of thyroid diseases. Although Tg is routinely measured as a marker for thyroid neoplasia and an adjunct in the diagnosis of thyrotoxicosis due to destructive thyroiditis, its clinical significance under conditions of abnormal thyroid function remains unclear.

We investigated the association between serum Tg levels and thyroid function in 292 patients who underwent simultaneous evaluation of serum Tg, free thyroxine (FT4), and free triiodothyronine (FT3) levels in routine clinical practice. Based on thyroid-stimulating hormone (TSH) levels, participants were classified into three groups: high-TSH (> 4.23 μIU/mL; n = 38), normal-TSH (0.61-4.23 μIU/mL; n = 191), and low-TSH (< 0.61 μIU/mL; n = 63).

The low-TSH group exhibited significantly higher serum Tg levels (118.66 ± 32.13 ng/mL) than the normal-TSH (70.20 ± 23.48 ng/mL) and high-TSH (34.70 ± 13.62 ng/mL) groups. Among patients positive for TSH-receptor antibodies (TRAb) or thyroid-stimulating antibodies (TSAb), elevated Tg levels were observed exclusively in the low-TSH group. Correlation analyses revealed that Tg levels were positively correlated with the FT3/FT4 ratio in the low-TSH group (rho = 0.62, p < 0.01), and this association was more evident in patients positive for both TRAb and TSAb (rho = 0.71, p < 0.01). These associations remained significant after multivariable adjustment and were supported by correlations between Tg and SPINA-GD, a model-based index of thyroid function reflecting deiodinase activity, with similar findings observed in patients with autoimmune hyperthyroidism.

These findings suggest that serum Tg levels may reflect biochemical features consistent with T3 predominance in autoimmune hyperthyroidism and have potential clinical utility in characterizing disease pathophysiology.