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Increased Thyroxine Sulfate Levels in Critically Ill Patients as a Result of a Decreased Hepatic Type I Deiodinase Activity

Department of Internal Medicine (R.P.P., M.H.A.K., E.K., H.v.T., T.J.V.), Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands; and Department of Intensive Care Medicine (P.J.W., G.V.d.B.), Catholic University of 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, Catholic University of Leuven, B-3000 Leuven, Belgium. E-mail: greta.vandenberghe{at}med.kuleuven.ac.be.

Introduction: Marked changes in peripheral thyroid hormone metabolism occur in critical illness, resulting in low serum T₃ and high rT₃ levels. In this study, we investigated whether T₄S levels are increased in patients who died after intensive care and whether T₄S levels are correlated with liver type I deiodinase (D1) or sulfotransferase (SULT) activity.

Methods: A total of 64 blood samples and 65 liver biopsies were obtained within minutes after death from 79 intensive care patients, randomized for intensive or conventional insulin treatment. Serum T₄S and the activities of hepatic D1 and 3,3'-diiodothyronine (T₂)-SULT and estrogen-SULT were determined.

Results: No differences in T₄S or hepatic SULT activities were found between patients treated with intensive or with conventional insulin therapy. T₄S levels were significantly elevated compared with healthy references. Furthermore, hepatic D1, but not SULT activity, showed a strong correlation with serum T₄S (R = –0.53; P < 0.001) and T₄S/T₄ ratio (R = –0.62; P < 0.001). Cause of death was significantly correlated with hepatic T₂- and estrogen-SULT activities (P < 0.01), with SULT activities being highest in the patients who died of severe brain damage and lowest in the patients who died of a cardiovascular collapse. A longer period of intensive care was associated with higher levels of T₄S (P = 0.005), and high levels of bilirubin were associated with low T₂-SULT (P = 0.04) activities and high levels of T₄S (P < 0.001).

Conclusion: Serum T₄S levels were clearly elevated compared with healthy references, and the decreased deiodination by liver D1 during critical illness appears to play a role in this increase in serum T₄S levels.

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