The importance of thyroglobulin levels in monitoring the treatment of congenital hypothyroidism

We have previously reported on high thyroid-stimulating hormone (TSH) concentrations in clinically euthyroid children with congenital (CH) undergoing appropriate treatment. Whether this TSH is biologically active or not is still unclear. It has been shown that ectopic thyroid tissue does not involute during thyroxine (T₄) therapy and thus can continue to secrete thyroglobulin (Tg). This study was undertaken to determine whether the Tg levels in ectopic CH infants represent residual thyroid tissue stimulated by biologically active TSH and whether this Tg can be used to help monitor CH treatment. Among the 51 primary CH children (age 2–14 years) diagnosed and followed up by us, 28 had measurable Tg values (> 2 pmol/l) several years after the T₄ treatment had been started. In 8 of the children, Tg was measured as early as the time of diagnosis and followed up for at least 3 years. The Tg levels decreased much more slowly than the TSH levels did, and secondary Tg rises were observed. By 5 months of age, all children had Tg levels less than 25 pmol/l. Although in some infants the Tg levels paralleled TSH behavior, in others the TSH-Tg correlation was not so obvious. In another group of 8 children who had high TSH values despite normal T₄, the LT₄ replacement dosage was increased by 60% for 1 week (from 3.5 ± 0.2 to 5.5 ± 0.5 μg/kg/day) in order to examine the TSH-Tg dependence. As a result, the serum levels of T₄ increased from 143 ± 10 to 176 ± 12 nmol/l, while the levels of TSH and Tg decreased from 8.1 ± 2.1 mU/l and 4.5 ± 0.5 ρmol/l to 1.7 ± 0.5 mU/l and 2.9 ± 0.6 pmol/l, respectively (p < 0.05). The data suggest that in primary CH children with ectopic thyroid tissue the residual gland is active and secretes Tg in response to endogenous TSH, years after the T₄ replacement treatment has been started. Therefore the high TSH found in some CH children despite adequate LT₄ replacement treatment is biologically active and easily suppressible with the increase in LT₄ dosage. Since Tg is TSH dependent and since Tg clearance is much slower compared to TSH clearance, Tg might be useful in monitoring more accurately the long-term compliance to the therapeutic protocol. Tg monitoring is especially valuable in those infants with fluctuating high TSH levels despite normal T₄ values.