Thyroxine Metabolism in the Low Thyroxine State of Critical Nonthyroidal Illnesses*

This study reports in vitro and in vivo parameters of T4 metabolism in patients with critical nonthyroidal illnesses who were selected because of serum total T4 values less than 3 micrograms/dl and normal TSH levels. Despite the depressed total T4 concentrations, the normal serum free T4 values (7 of 9 patients), T4 production rates (8 of 9), and TSH responses to TRH (8 of 8) provided evidence for normal free T4 availability to peripheral tissues. Elevated rT3 values in 10 of 14 patients were consistent with this view. However, serum free T4 index determinations markedly underestimated free T4 (20 of 20). This resulted from failure of the T3 uptake measurement to reflect the defective state of serum T4 binding. Defective serum T4 binding to carrier proteins was evidenced by the 2- to 3-fold increase in both the free fraction and the MCR values for T4. The normal early distribution phase, despite defective serum T4 binding, suggested an additional abnormality of deficient extravascular T4 binding. The blunted TSH response to TRH and the low normal values for both T4 production rates and free T4 levels measured by equilibrium dialysis indicated mild pituitary suppression, possibly related to elevated serum cortisol levels. Since an overt deficiency of free T4 availability does not appear to exist in the low T4 state of critical nonthyroidal illness, T4 therapy cannot currently be recommended.