Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat

We have recently shown that it is not possible to restore euthyroidism completely in all tissues of thyroidectomized rats infused with T-4 alone. The present study was undertaken to determine whether this is achieved when T-3 is added to the continuous sc infusion of T-4. Thyroidectomized rats were infused with placebo or T-4 (0.80 and 0.90 micrograms/100 g BW-day), alone or in combination with T-3 (0.10,0.15, or 0.20 micrograms/100 g BW-day). Placebo-infused intact rats served as euthyroid controls. Plasma and 12 tissues were obtained after 12 days of infusion. Plasma TSH and plasma and tissue T-4 and T-3 were determined by RIA. Iodothyronine deiodinase activities were assayed using cerebral cortex, pituitary, brown adipose tissue, liver, and lung. Circulating and tissue T-4 levels were normal in all the groups infused with thyroid hormones. On the contrary, T-3 in plasma and most tissues and plasma TSH only reached normal levels when T-3 was added to the T-4 infusion. The combination of 0.9 microgram T-4 and 0.15 microgram T-3/100 g BW-day resulted in normal T-4 and T-3 concentrations in plasma and all tissues as well as normal circulating TSH and normal or near-normal 5'-deiodinase activities. Combined replacement therapy with T-4 and T-3 (in proportions similar to those secreted by the normal rat thyroid) completely restored euthyroidism in thyroidectomized rats at much lower doses of T-4 than those needed to normalize T-3 in most tissues when T-4 alone was used. If pertinent to man, these results might well justify a change in the current therapy for hypothyroidism.