Thyroxine Binding Proteins, Free Thyroxine and Thyroxine Turnover Interrelationships during Acute Infectious Illness in Man1

Abstract
Serial measurements of the serum concentrations (as maximum binding capacities) of thyroxine binding prealbumin (TBPA), thyroxine binding globulin (TBG), PBI, free T4 (FT4), and percent free T4 (% FT4) were made before, during and after experimental infections (typhoid fever, tularemia and malaria) in 15 human subjects. In addition, the rate of disappearance of 125I-T4 from the circulation was determined. TBPA decreased during illness, but large initial decreases were dissociated in time from changes of FT4 and % FT4. Occasional but significant changes of TBG and PBI were unrelated to changes of TBPA and % FT4. PBI often dropped after the onset of illness, followed by a rebound which exceeded control values. These alterations of PBI alone resulted in significant FT4 changes in six cases. In two cases (malaria and shigeliosis) % FT3 changes paralleled changes of % FT4. In five subjects (two with typhoid fever and three with tularemia) increases of FT4 were not associated with any change in the rate of 125I-T4 disappearance from the circulation. In ten subjects (three typhoid fever, two tularemia and five malaria) acceleration and/or slowing of 125I-T4 disappearance was seen at some time during the course of illness. However, the time relationships indicated that the fluctuations of serum FT4 in these subjects were not causally related to the alterations of 125I-T4 disappearance. The changes of % FT4 and FT4 during infectious illness are not the consequence of changes of TBPA or TBG concentration. Our data suggest that during this stress increased FT4 results not from altered concentration of the thyroxine binding proteins of serum but rather from the appearance of an inhibitor of T4 binding.