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Heterogeneity in affinities of serum proteins for thyroxine among patients with non-thyroidal illness as indicated by the serum free thyroxine response to serum dilution

Wilcox RB, Nelson JC, Tomei RT. Heterogeneity in affinities of serum proteins for thyroxine among patients with non-thyroidal illness as indicated by the serum free thyroxine response to serum dilution. Eur J Endocrinol 1994;131:9–13. ISSN 0804–4643

Some patients with non-thyroidal illness (NTI) have sera with characteristics suggesting decreased functional affinity of thyroxine-binding globulin (TBG) for T₄: increased T₄ free fraction, decreased total T₄ to TBG ratio, and a fall in free T₄ with serum dilution greater than theoretical predictions assuming normal affinity. These studies aimed to further characterize this phenomenon. According to the law of mass action binding protein affinity for T₄ can be estimated from the response of free T₄ to progressive serum dilution. Free T₄ responses in 25 normal controls and in 7 congenital TBG deficient controls resembled the predictions from the law of mass action. Among 25 of 38 medical intensive care unit patients, responses were intermediate between normals and TBG deficiency. Responses in the other 13 NTI were consistent with the presence of a dissociable inhibitor. In this subgroup, total T₄ was depressed, both free T₄ and TSH were elevated, and there was a positive correlation between TSH and free T₄ (r² = 0.41, p < 0.02). Conclusions: (i) decreased affinities of serum proteins for T₄ consistent with binding inhibitor(s) are found in some patients with NTI; (ii) there is an association of these severely altered affinities with reversal of the expected free T₄–TSH relationship.

R Bruce Wilcox, Department of Biochemistry, Loma Linda University, Loma Linda, CA 92350 USA

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