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Regulation of type 1 deiodinase activity in prolonged critical illness


The low T3 syndrome invariably observed in prolonged critically ill patients can be explained at least in part by reduced hepatic type 1 deiodinase (D1) activity, whereby the T4 metabolism is shunted away from T3 production into inactive rT3. Infusion of TRH, however, restores the catalytic activity of D1 and concomitantly increases T3 to within the physiological range, indicating that D1 activity during critical illness is regulated via alterations within the thyroid axis [1].

It remains unknown, however, whether this observed reactivation of D1 activity is due to either a direct effect of TRH or the induced rise in circulating T4 and T3 concentrations.


Burn-injured, parenterally fed, New Zealand White rabbits were randomized to receive a 4-day infusion of saline, T4 (9 μg/kg/day), T3 (5 μg/kg/day), T4 + T3 or TRH (60 μg/kg/hour). The doses of T4 and T3 aimed at, respectively, bringing plasma T4 and T3 levels into the range obtained by TRH infusion. Endocrine and biochemical organ system markers were studied. Animals were sacrificed for the assay of deiodinase activity in snap-frozen liver.


Compared with infusion of saline, rabbits receiving T4, T3 and TRH exhibited higher hepatic D1 activities and subsequent elevated T3 levels. Coinfusion of T3 with T4, however, evoked an additional increase in hepatic D1 activity (P = 0.07) with increased T4 to T3 conversion as demonstrated by significantly lower T4 (P = 0.002, T4 + T3 vs T4), higher T3 (P = 0.004, T4 + T3 vs T3) and lower rT3 levels (P = 0.001, T4 + T3 vs T4). Hepatic D1 activity was strongly correlated with plasma T3 (R = 0.871, P < 0.0001) but not with T4, rT3 and TSH concentrations.


D1 activity during prolonged critical illness is most probably regulated via alterations in plasma T3.


  1. Debaveye Y, et al.: Endocrinology. 2005, 146: 5604-5611. 10.1210/en.2005-0963

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Debaveye, Y., Ellger, B., Mebis, L. et al. Regulation of type 1 deiodinase activity in prolonged critical illness. Crit Care 10 (Suppl 1), P266 (2006).

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