Exp. Clin. Endocrinol. Vol. 95, No. 2, 1990, pp. 267-270
J. A. Barth, Leipzig
Department of Endocrinology (Head: Prof. Dr. med. K. Schöffling), Center of Internal Medicine, and *Department of Experimental Anaesthesiology, University Hospital, Frankfurt am Main/FRG
Thyroid Hormone Binding Inhibition in Critically ill Patients E. SCHIFFERDECKER, S. HERING, B. O. BÖHM, H. FÖESTER*, P.-H. ALTHOFF, F. SCHULZ and K. SCHÖFFLING
Summary. In 31 severely ill patients of our intensive care unit an increased thyroid hormone binding inhibition detected by quantitative measurement of the effect of ether extraóts of patients' sera on thyroxine tracer binding to TBG was found. As free fatty acids in serum were diminished in these patients, their postulated role as binding inhibitors in the "low T4 syndrome" of critically ill patients must be questioned. It cannot be excluded that THBI assays demonstrating this inhibition measure artefacts caused by heparine-induced in vitro lipolysis.
Key words: Thyroid hormone binding inhibition - Low T4 syndrome - Critical illness Free fatty acids
Introduction
The cause of the "low T4 syndrome" detectable in severely ill patients is still unclear. Displacement of thyroxine (T4) from its binding proteins by fatty acids is under discussion. 1984 Chopra et al. reported a method to quantify T4 binding inhibition, and by adding certain free fatty acids in vitro, Chopra et al. (1985) were able to demonstrate an increase in inhibitory activity. Own data revealed a decrease of serum levels of free fatty acids (FFA) on the whole in the course of critical illness compared to normal controls, thus calling into question the role of FFA as binding inhibitors in vitro (Schifferdecker et al., 1988).
In the additional study presented here THBI activity in the sera of critically ill patients with diminished FFA levels was analyzed in order to gain further information on the nature of thyroid hormone binding inhibition. Methods 31 patients of our intensive care unit (ICU) suffering from acute severe illness, i.e. cardiovascular diseases (n = 12), gastrointestinal problems (n 6), respiratory failure (n = 3), septicemia (n 4) metabolic crisis (n = 2) and miscellaneous diseases (n = 4) were examined. 21 patients died in the course of the disease after 2 to 33 days (mean: 10.2 days), 27 had to be treated with dopamine, all patients but four received heparine from the beginning of treatment. Blood was. drawn regulnrly, at first within 12 hours after admission to the ICU, for analysis of T3 (Triiodothyronine), T4, free T4, TBG and the pattern of free fatty acids (FFA) by gas chromatography as described previously
Downloaded by: University of Pittsburgh. Copyrighted material.
Who is the Inhibitor?
268
Exp. Clin. Endocrinol. 95 (1990) 2
(Schifferdecker et al., 1988). Thyroid hormone binding inhibitqry activity (THBI) was measured using a modification of Chopra's method (Chopra et al., 1984) proposed by Herrmann et al. (1985). Briefly, ether extracts of patients' sera thus depleted of thyroid hormones were evaporated to dryness under nitrogen. 300 buffer containing TBG antibodies attached to glass. 3 l T4-free serum and 100 l of 125J-T4 were added. After incubation for 1 h and centrifugation for 10 min radioactivity in the pellet was measured in a gamma counter. Displacement of T4 tracer by merthiolate was employed to produce standard curves, thus allowing to quantify binding inhibition as ig merthiolate equivalent per 1il (pig MEqJ1il).
Data are presented as mean ± standard deviation, Wilcoxon's test is used to detect significant differences between patients' subgroups, 2 = 0.05 was chosen as minimum level of significance.
Results of FFA analysis and thyroid function data in the 31 patients of the series have been presented recently (Schifferdecker et al., 1988). Briefly, only palmitolenic acid was significantly elevated in the beginning of the observation period, all other FFA were diminished compared to a control group of 174 persons. FFA levels in patienta not surviving were lower than in survivors and decreased further during observation. T4 serum levels were shown to be significantly lower than in a control group, in 10 patients T4 was subnormal (
J. A. Barth, Leipzig
Department of Endocrinology (Head: Prof. Dr. med. K. Schöffling), Center of Internal Medicine, and *Department of Experimental Anaesthesiology, University Hospital, Frankfurt am Main/FRG
Thyroid Hormone Binding Inhibition in Critically ill Patients E. SCHIFFERDECKER, S. HERING, B. O. BÖHM, H. FÖESTER*, P.-H. ALTHOFF, F. SCHULZ and K. SCHÖFFLING
Summary. In 31 severely ill patients of our intensive care unit an increased thyroid hormone binding inhibition detected by quantitative measurement of the effect of ether extraóts of patients' sera on thyroxine tracer binding to TBG was found. As free fatty acids in serum were diminished in these patients, their postulated role as binding inhibitors in the "low T4 syndrome" of critically ill patients must be questioned. It cannot be excluded that THBI assays demonstrating this inhibition measure artefacts caused by heparine-induced in vitro lipolysis.
Key words: Thyroid hormone binding inhibition - Low T4 syndrome - Critical illness Free fatty acids
Introduction
The cause of the "low T4 syndrome" detectable in severely ill patients is still unclear. Displacement of thyroxine (T4) from its binding proteins by fatty acids is under discussion. 1984 Chopra et al. reported a method to quantify T4 binding inhibition, and by adding certain free fatty acids in vitro, Chopra et al. (1985) were able to demonstrate an increase in inhibitory activity. Own data revealed a decrease of serum levels of free fatty acids (FFA) on the whole in the course of critical illness compared to normal controls, thus calling into question the role of FFA as binding inhibitors in vitro (Schifferdecker et al., 1988).
In the additional study presented here THBI activity in the sera of critically ill patients with diminished FFA levels was analyzed in order to gain further information on the nature of thyroid hormone binding inhibition. Methods 31 patients of our intensive care unit (ICU) suffering from acute severe illness, i.e. cardiovascular diseases (n = 12), gastrointestinal problems (n 6), respiratory failure (n = 3), septicemia (n 4) metabolic crisis (n = 2) and miscellaneous diseases (n = 4) were examined. 21 patients died in the course of the disease after 2 to 33 days (mean: 10.2 days), 27 had to be treated with dopamine, all patients but four received heparine from the beginning of treatment. Blood was. drawn regulnrly, at first within 12 hours after admission to the ICU, for analysis of T3 (Triiodothyronine), T4, free T4, TBG and the pattern of free fatty acids (FFA) by gas chromatography as described previously
Downloaded by: University of Pittsburgh. Copyrighted material.
Who is the Inhibitor?
268
Exp. Clin. Endocrinol. 95 (1990) 2
(Schifferdecker et al., 1988). Thyroid hormone binding inhibitqry activity (THBI) was measured using a modification of Chopra's method (Chopra et al., 1984) proposed by Herrmann et al. (1985). Briefly, ether extracts of patients' sera thus depleted of thyroid hormones were evaporated to dryness under nitrogen. 300 buffer containing TBG antibodies attached to glass. 3 l T4-free serum and 100 l of 125J-T4 were added. After incubation for 1 h and centrifugation for 10 min radioactivity in the pellet was measured in a gamma counter. Displacement of T4 tracer by merthiolate was employed to produce standard curves, thus allowing to quantify binding inhibition as ig merthiolate equivalent per 1il (pig MEqJ1il).
Data are presented as mean ± standard deviation, Wilcoxon's test is used to detect significant differences between patients' subgroups, 2 = 0.05 was chosen as minimum level of significance.
Results of FFA analysis and thyroid function data in the 31 patients of the series have been presented recently (Schifferdecker et al., 1988). Briefly, only palmitolenic acid was significantly elevated in the beginning of the observation period, all other FFA were diminished compared to a control group of 174 persons. FFA levels in patienta not surviving were lower than in survivors and decreased further during observation. T4 serum levels were shown to be significantly lower than in a control group, in 10 patients T4 was subnormal (
