To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma T2 and T4S, deiodinase type 1 (D1) and D3 activity and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2 expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T4 and T3, either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH.

Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T3 (P=0.006), hepatic T3 (P=0.02) and hepatic D1 activity (P=0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P=0.0006) and tissue T4 (P=0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T3 and tissue T3/rT3 ratio correlated with deiodinase activities. Neither substitution nor high-dosed treatment altered plasma T2. Plasma T4S was only increased by T4 in high dose.

We conclude that in prolonged critically ill rabbits, low plasma T3 levels were associated with low liver and kidney T3 levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose, but instead required several fold this dose. This indicates thyroid hormone hypermetabolisation, which in this model of critical illness is not entirely explained by deiodination nor by sulfoconjugation.