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Effects of Substitution and High-Dose Thyroid Hormone Therapy on Deiodination, Sulfoconjugation, and Tissue Thyroid Hormone Levels in Prolonged Critically Ill Rabbits

Department of Intensive Care Medicine (Y.D., B.E., L.M., G.V.d.B.), Laboratory of Comparative Endocrinology (V.M.D.), Catholic University of Leuven, B-3000 Leuven, Belgium; Department of Internal Medicine (T.J.V.), Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands; and Department of Anesthesiology and Intensive Care Medicine (B.E.), University Hospital of Muenster, D-48149 Muenster, Germany

Address all correspondence and requests for reprints to: Greet Van den Berghe, M.D., Ph.D., Department of Intensive Care Medicine, Catholic University of Leuven, B-3000 Leuven, Belgium. E-mail: greet.vandenberghe{at}med.kuleuven.be.

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 3,3'-diiodothyronine (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/reverse T₃ ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T₂. Plasma T₄S was increased only 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 severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation.

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