HETEROGENEITY IN AFFINITIES OF SERUM-PROTEINS FOR THYROXINE AMONG PATIENTS WITH NONTHYROIDAL ILLNESS AS INDICATED BY THE SERUM-FREE THYROXINE RESPONSE TO SERUM DILUTION

Some patients with non-thyroidal illness (NTI) have sera with characte ristics suggesting decreased functional affinity of thyroxine-binding globulin (TBG) for T-4: increased T-4 free fraction, decreased total T -4 to TBG ratio, and a fall in free T-4 with Serum dilution greater th an theoretical predictions assuming normal affinity. These studies aim ed to further characterize this phenomenon. According to the law of ma ss action binding protein affinity for T-4 can be estimated from the r esponse of free T-4 to progressive serum dilution. Free T-4 responses in 25 normal controls and in 7 congenital TBG deficient controls resem bled the predictions from the law of mass action. Among 25 of 38 medic al intensive care unit patients, responses were intermediate between n ormals and TBG deficiency. Responses in the other 13 NTI were consiste nt with the presence of a dissociable inhibitor. In this subgroup, tot al T-4 was depressed, both free T-4 and TSH were elevated, and there w as a positive correlation between TSH and free T-4 (r(2) = 0.41, p < 0 .02). Conclusions: (i) decreased affinities of serum proteins for T-4 consistent with binding inhibitor(s) are found in some patients with N TI; (ii) there is an association of these severely altered affinities with reversal of the expected free T-4-TSH relationship.