Thyroxine Plus Low-Dose, Slow-Release Triiodothyronine Replacement in Hypothyroidism: Proof of Principle

Studies in hypothyroid rats show that, when infused with a combination of thyroxine (T4) plus triiodothyronine (T3) to normalize thyrotropin (TSH), euthyroidism in all organs is only ensured when T4 and T3 are administered in a ratio as normally secreted by the rat thyroid. As substitution with T4-only results in an abnormal serum T 4/T3 ratio, it is also possible that in humans, euthyroidism does not exist at the tissue level in many organs, considering that iodothyronine metabolism in the human and the rat share many similar mechanisms. Recent reports in which cognitive function and well-being are compared in patients with primary hypothyroidism substituted with T 4-only versus substitution with T4 plus T3 result in controversial findings in that either positive or no effects were found. In all these studies T3 was used in the plain form that results in non-physiologic serum T3 peaks. In these studies it is suggested that substitution with T3 should preferably be performed with a preparation that slowly releases T3 to avoid these peaks. In the study reported here we show that treatment of hypothyroid subjects with a combination of T4 plus slow-release T3 leads to a considerable improvement of serum T4 and T3 values, the T4/T3 ratio and serum TSH as compared to treatment with T4-only. Serum T3 administration with slow-release T 3 did not show serum peaks, in contrast to plain T3.

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