Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations

Abstract

Although the normal thyroid gland secretes both levothyroxine (L-T₄) and levotriiodothyronine (L-T₃), normalization of serum TSH with LT₄-replacement therapy alone in hypothyroidism is generally believed to result in a normal serum L-T₃ and to reflect a euthyroid state. However several recent studies suggest that this may not be the case,. Accordingly, the relationship between serum free L-T₄ and free L-T₃ was examined in 20 normal individuals (group A) and in 53 patients with chronic autoimmune thyroiditis, 18 with normal TSH on no L-T₄-replacement (group B), and 35 with normal TSH on L-T₄-replacement therapy for hypothyroidism (group C). Data were analyzed by applying a one-way analysis of variance with correction for multiple comparisons. Serum TSH values were very similar among the 3 groups. In groups A and B, mean serum free T₄ and free T₃ were very similar. In group C, the mean free T₄ (16±2 pmol/l) was significantly higher than the values in groups A (14±1) and B (14±2) (p<0.001) and the mean free T₃ lower (4.0±0.5 pmol/l vs 4.2±0.5, NS and 4.4±0.5, p<0.02). Consequently, the mean molar ratio of free T₄ to free T₃ was significantly higher in group C than the ratios in groups A and B (p<0.0001), despite very similar TSH values. These findings indicate that in hypothyroid patients L-T₄-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T₄ that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T₃ concentration.