T4 plus T3 treatment in children with hypothyroidism and inappropriately elevated thyroid-stimulating hormone despite euthyroidism on T4 treatment.

Aims: To evaluate the effect of addition of T3 to L-T4 treatment in children with congenital hypothyroidism (CH) who have inappropriately elevated thyroid-stimulating hormone (TSH) levels despite high normal serum T4 levels on L-T4 treatment.

Methods: Ten children (age 7.1 +/- 2 years) with CH whose TSH levels were persistently high despite euthyroidism and can only be normalized with hyperthyroidism were included. L-T4 treatment was switched to T3+L-T4 combination (Bitiron(R) tablet 50 mug L-T4 + 12.5 mug triiodothyronine). The patients received 50% of their usual L-T4 dose as L-T4 and the remaining half as T3 in a 4:1 ratio. The dose of T3+L-T4 was titrated to achieve normal TSH levels. Thyroid hormones and biochemical markers were followed for 1 year.

Results: Euthyrotropinemia was achieved at the 7th month (mean) of combination (T3+L-T4) treatment. Serum T4 and fT4 were lower and T3 was higher during combination compared to L-T4 treatment. LDL-cholesterol decreased and ALP increased in the euthyrotropinemic state. Vital signs were similar at hyperthyrotropinemia and euthyrotropinemia.

Conclusion: T3+L-T4 treatment provides euthyrotropinemia without causing hyperthyroidism in children with CH and inappropriate hyperthyrotropinemia. Our data strongly suggest that decreased negative feedback due to lower T3 levels at the pituitary level is the main reason for persistent hyperthyrotropinemia.