Increased thyroxine sulfate levels in critically ill patients as a result of a decreased hepatic type I deiodinase activity

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.