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Tissue Thyroid Hormone Levels in Critical Illness

Department of Internal Medicine (R.P.P., H.v.T., E.K., T.J.V.), Erasmus University Medical Center, Rotterdam, The Netherlands; and Laboratory of Comparative Endocrinology, Zoological Institute (S.v.d.G., V.M.D.) and Department of Intensive Care Medicine (P.J.W., G.V.d.B.), Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

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

Context: Pronounced alterations in serum thyroid hormone levels occur during critical illness. T₃ decreases and rT₃ increases, the magnitudes of which are related to the severity of disease. It is unclear whether these changes are associated with decreased tissue T₃ concentrations and, thus, reduced thyroid hormone bioactivity.

Patients and Study Questions: We therefore investigated, in 79 patients who died after intensive care and who did or did not receive thyroid hormone treatment, whether total serum thyroid hormone levels correspond to tissue levels in liver and muscle. Furthermore, we investigated the relationship between tissue thyroid hormone levels, deiodinase activities, and monocarboxylate transporter 8 expression.

Results: Tissue iodothyronine levels were positively correlated with serum levels, indicating that the decrease in serum T₃ during illness is associated with decreased levels of tissue T₃. Higher serum T₃ levels in patients who received thyroid hormone treatment were accompanied by higher levels of liver and muscle T₃, with evidence for tissue-specific regulation. Tissue rT₃ and the T₃/rT₃ ratio were correlated with tissue deiodinase activities. Monocarboxylate transporter 8 expression was not related to the ratio of the serum over tissue concentration of the different iodothyronines.

Conclusion: Our results suggest that, in addition to changes in the hypothalamus-pituitary-thyroid axis, tissue-specific mechanisms are involved in the reduced supply of bioactive thyroid hormone in critical illness.

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