Changes in serum triiodothyronine, thyroxine, and thyrotropin during treatment with thyroxine in severe primary hypothyroidism.

Studies were performed on 40 patients with severe primary hypothyroidism, during treatment with varying doses of T4. Therapy was initiated with 50 mug/day and was continued for at least 2 months. Subsequent repeated increases of 25 mug/day were continued for at least 2 months until the serum TSH level was less than 10 muU/ml. Measurements of serum T4 and T3, RT3U, and serum TSH were carried out at monthly intervals. TRH tests were performed after TSH levels of less than 10 muU/ml had been attained and the dose of T4 had been maintained for at least 2 months. In most of the samples obtained during treatment with various doses of T4 (50-175 mug/day), serum T4 concentrations were within the normal range, even when patients were receiving only 50 mug/day of T4; however, approximately 60% of the samples had subnormal T3 concentrations. Fifty per cent of the samples had elevated TSH concentrations despite normal T4 levels, while only 7% of the samples with normal T3, as well as T4, levels had slightly elevated TSH concentrations. Similar relationships were observed between serum TSH and free T4 indices and free T3 indices. Among patients with serum TSH levels of less than 10 muU/ml, none showed subnormal T4 concentrations, while subnormal T3 concentrations were found in some of them. Hyper-response to TRH was noted in patients with subnormal T3 levels, and normal responses were observed in patients with normal T3 and T4 concentrations. These data indicate that, during the treatment of hypothyroidism with T4, 1) normal basal TSH correlates better with normal serum T4 and T3 than with normal T4 alone, 2) the response of TSH to TRH is supranormal in patients with subnormal T3 levels, in spite of normal basal TSH and T4, and 3) the calculated maintenance dose of T4, which is associated with a normal TRH response, is 2.08 mug/day/kg of body weight.