Objectives: Non-thyroidal illness (NTI) is frequently accompanied by alterations in circulating thyroid hormone concentrations, despite patients remaining clinically euthyroid. The mechanisms accounting for these changes in circulating thyroid hormone concentrations remain unknown. Much attention has focussed on the role of inflammatory cytokines which are known to be important mediators of disease. The aim of this study was to investigate the role of the cytokine interleukin-6 (IL-6) in alterations of thyroid hormone metabolism seen in NTI.
Design: Longitudinal study of hospital in-patients, correlating serum IL-6 concentrations with circulating thyroid hormone concentrations.
Patients: Two hundred and seventy in-patients recruited consecutively, excluding those with known or suspected thyroid disorder. The patients were divided into 5 subgroups reflecting the nature of their NTI and comprised 41 patients with liver disease, 99 with renal disease, 19 intensive care (ITU) patients, 22 with cardiac disease and 89 patients with general medical, or surgical conditions.
Measurements: Serum IL-6 concentrations were determined using a commercially obtained immunoassay (IL-6 Quantikine assay, R&D Systems, Abingdon, UK). Serum total T4 and total T3 were measured using chemiluminescent immunometric assays (Kodak Clinical Diagnostics Ltd, Amersham, UK) and serum TSH was measured using a third-generation chemiluminescent immunometric assay (Amerlite TSH 30, Kodak Clinical Diagnostics Ltd, Amersham, UK).
Results: Ninety-three patients studied (35%) had a serum T3 below the normal range (<1.0 nmol/l), 89 patients (33%) had a serum T4 below the normal range (<65 nmol/l) and in 58 patients (21%) both serum T3 and T4 were below the normal range. There was a significant negative correlation between serum total T3 and IL-6 (r = -0.219; P < 0.001) and total T4 and IL-6 (r = -0.32; P = 0.32), but not between TSH and IL-6 (r = -0.075; P = 0.22). The ITU patient subgroup had the highest IL-6 concentrations (229.3 +/- 48.1 ng/l, mean +/- standard error), whilst also having the lowest T3 (0.93 +/- 0.08 nmol/l), TSH (0.79 +/- 0.25 mU/l) and T4 concentrations (66.6 +/- 7.3 nmol/l). The subgroup of patients under general medical or surgical care had least disturbance of their T3 (low in 19%) and T4 (low in 8%) concentrations, whilst also having the lowest mean IL-6 concentration (39.0 +/- 5.3 ng/l). The renal patient subgroup, whilst including a high proportion of patients with low T3 (39%) and T4 (45%) concentration, demonstrated only modest elevation of IL-6 concentrations (mean 41.4 +/- 8.5 ng/l).
Conclusions: Our data revealed a statistical relation between elevated serum IL-6 concentrations and alterations in circulating thyroid hormone concentrations seen in NTI; however, the findings in patients with renal disease suggest that circulating IL-6 is not the only factor responsible for alteration in thyroid hormone metabolism in NTI.