Randomized Clinical Trial Of Combined Thyroxine/Triiodothyronine Treatment In Thyroidectomised Patients With Differentiated Thyroid Carcinoma

Background There are two hormones excreted by thyroid, thyroxine and triiodothyronine. The daily production amount of thyroxine is about 100 microgram, all produced by the thyroid gland. The daily production amount of triiodothyronine is about 30 microgram, of which about 20 percent is produced by the thyroid gland and 80 percent by deiodination of thyroxine in extrathyroidal tissues. Not all tissues that need thyroid hormone are equally able to convert thyroxine to triiodothyronine, the active form of the hormone. Nevertheless, most of patients with hypothyroidism are treated only with thyroxine (levothyroxine). Although this treatment is effective, some patients with hypothyroidism treated with thyroxine are not entirely well. Some patients complain their symptoms of hypothyroidism persist in spite of their normal thyroid hormone levels in serum. Recent animal studies show that no single dose of T₄ can restore normal plasma thyrotropin, T₄ and T₃, as well as T₄ and T₃ in all tissues, or at least to restore T3 simultaneously in plasma and all tissues. Moreover, in most tissues, the dose of T₄ needed to ensure normal T₃ levels resulted in supraphysiological T₄ concentrations. Some clinicaltrials compared the effects of combined T4/T3 treatment with T4 alone in patients with hypothyroidism. Some researchers found combination treatment was associated with improved mood, well-being, and measures of cognitive function compared to thyroxine alone. On the contrary, others showed that combination treatment demonstrated no beneficial changes in body weigh, serum lipid levels, hypothyroidism symptoms and cognitive performance. So we conducted this controlled trial to further investigate whether combined therapy with triiodothyronine and levothyroxine would lead to improvement in mood, cognitive functions, physiological and biological tests.Methods We compared the effects of thyroxine alone with those ofthyroxine plus triiodothyronine in 45 patients with hypothyroidism. These patients with thyroid cancer were receiving replacement therapy with thyroxine after total thyroidectomy and radioiodine ablation therapy. The neuropsychological, physiological and biological tests were performed in those patients.Then they were divided into three groups by random, the first group receiving treatment with thyroxine plus placebo, the second group receiving treatment with combined thyroxine/T3 in which 25 u g of thyroxine was replaced by 6.25 u g T3, the third group receiving treatment with combined thyroxine/T3 in which 25 u g of thyroxine was replaced by 25 u g T3. After three months, the tests of neuropsychological, physiological and biological were performed again.Results The patients had lower serum thyroid hormones concentrations and higher TSH and hTg concentrations after withdrew thyroxine 30 days. Their scores of SCL-90 and the scores of Hamilton scale increased afterwithdral of thyroxine. The concentrations of serum TG, CHOL, LDL-C, ApoBlOO, LP(a) increased but concentrations of ApoAl and HDL-C decreased. After 3 months treatment, serum total and free thyroxine and triiodothyronine levels all increased while TSH and hTg levels decreased. There were significant difference in monotherapy and combined therapy but no significant difference in the two combined therapy. After 3 months, the scores of SCL-90, Hamilton scale and cognitive functions improved to some extent but there are no significant difference among these 3 groups. Compared with monotherapy, treatment with 25 u g substituting 25 u g thyroxine significantly increased patients' heart rate and blood pressure. Both monotherapy and combined therapy could decrease serum lipid such as TG, CHOL, LDL-C, ApoBlOO and LP(a) whereas elevated HDL-C and ApoAl. The effects of combined treatment is more significant than those of monotherapy.Conclusions Short-term withdrawal of thyroxine caused negativeinfluence on patients' psychiatry, serum lipid and cardiovascular system. Replacement with thyroid hormone improved patient's mood and reduce risk factors of cardiovascular disease. Effects of TSH suppression in patients with combined therapy were better than that of monotherapy. However, compared with levothyroxine alone, treatment of primary hypothyroidism with combination levothyroxine plus triiodothyronine demonstrated no beneficial changes in cognitive functions, psychological well-being and mood.