Serum thyroid hormone binding inhibitor in nonthyroidal illnesses

Abstract

We have employed the recently developed competitive ligand binding assay (CLBA) to study thyroid hormone binding inhibitor (THBI) in ether extracts of sera of 25 patients admitted to the Medical Intensive Care Unit with a variety of nonthyroidal illnesses (NTI). THBI was detected in 60% ( 15 25 ) of patients using one sample/patient and in 88% ( 15 17 ) using multiple (two to six) samples from different days. Mortality rate and mean serum concentrations of total T 4, total T 3, and albumin were similar in THBI-positive and THBI-negative patients. There was a tendency for a higher frequency of low serum total T 4 in THBI-positive ( 10 15 ) than in THBI-negative ( 3 10 ) patients but the difference was not statistically significant ( P < 0.1 by Chi square). However, the mean dialyzable fraction of T 4 (DFT 4 0.11 ± 0.02%, n = 9 v 0.054 ± 0.004%, n = 10) and DFT 3 (0.54 ± 0.05% v 0.40 ± 0.032%) were both significantly ( P < 0.05) higher in THBI-positive patients than THBI-negative patients. There was a significant correlation between THBI and DFT 4 ( r = 0.55, P < 0.02) or DFT 3 ( r = 0.54, P < 0.02). Prior extraction of serum with ether reduced DFT 4 in NTI patients with high baseline DFT 4 but not in normal subjects or NTI patients with mildly abnormal baseline DFT 4. Addition to a normal serum (0.1 mL) of evaporated ether extract of a pooled NTI serum (0.10- to 3.0-mL equivalent) increased DFT 4 progressively from 0.025% to 0.14%. Similar extract of a pooled serum of normal subjects had little or no effect. THBI caused a 2.1 to 3.7 fold greater increase above baseline in DFT 4 than in DFT 3 of a pooled normal serum. Addition of THBI to a normal serum increased its DFT 4 by 35 to 377% but increased the resin uptake of T 3 (RT 3U) only by 18 to 37%. THBI reduced T 4 binding activity of TBG, albumin or prealbumin in the CLBA. The effect of THBI on T 4 binding activity of TBG was also studied in the competitive protein binding assay of Murphy and Patee. Scatchard plots of the data suggested that THBI reduces T 4 binding to TBG by reducing its affinity for T 4. In the CLBA, THBI activity of ether extract of NTI serum was increased ∼threefold by reducing the amount of albumin from 4.5 mg to 1.5 mg per assay tube. Similarly, THBI was more active when charcoal-treated NTI serum was used in place of charcoal-treated normal serum in the CLBA. The various data suggest that: (1) THBI is present very commonly in sera of NTI patients; (2) THBI inhibits T 4 binding to all three T 4-binding serum proteins; (3) THBI may contribute to high DFT 4, high DFT 3 and the frequently observed discrepancy between DFT 4 and RT 3U in NTI; and (4) Low serum albumin in NTI may enhance the activity of THBI.