Elevated Serum Diiodotyrosine (DIT) in Severe Infections and Sepsis: DIT, a Possible New Marker of Leukocyte Activity*

Abstract

Ether link cleavage (ELC) of T4 yielding diiodotyrosine (DIT) has recently been shown in vitro to be the major pathway of T4 metabolism in phagocytosing leukocytes. To evaluate this pathway in vivo and the possible clinical relevance of DIT measurements in diseases with increased leukocyte activity, radioimmunological studies on serum levels of DIT and other thyroid parameters were performed in 125 critically ill patients classified into 3 groups with bacterial infections according to the severity of infection and 1 group without infections. While the pattern of iodothyronine and TSH levels typical for severe nonthyroidal disorders, i.e. decreased total T3 and elevated rT3, normal or decreased total T4 and TSH, and normal free T4, was found in all four groups of intensive care patients studied, elevated serum DIT was observed only in those patients whose clinical course was complicated by severe bacterial infections. Serial measurements revealed a close temporal connection between the infection phase and increased DIT levels. Median values and 16th to 84th percentile ranges (in parentheses) of serum DIT (normal range, 0.02-0.55 nmol/L) were as follows: sepsis, 1.38 (0.32-5.14); severe nonsystemic infections such as peritonitis and abscesses, 3.84 (0.24-17.2); moderate infections such as pneumonia and tracheobronchitis, 0.44 (0.18-1.16); and critical illness without infections, 0.14 (0.08-0.30) nmol/L. These elevations of circulating DIT could neither be correlated with changes in renal function nor attributed to drug effects. The results of the present study do not allow any definitive conclusions to be made about the mechanisms underlying the phenomenon of increased serum DIT levels in infections. Apart from this open question, DIT appears to be a relatively specific serum parameter for the presence and course of severe bacterial inflammations. Its measurement could provide useful clinical information, particularly for monitoring the time course of deep-seated infections.

The molecular basis of the non-thyroidal illness syndrome

“…The role of ECL in TH metabolism under physiological conditions is thought to be limited, since only 5% of total body clearance of TH is mediated via ELC (Faber et al 1989). However, it has been suggested that the serum concentration of DIT, a product of ELC, increase after surgery and during sepsis (Gramm et al 1989, Meinhold et al 1991, indicating that in specific pathophysiological conditions, ECL might attribute to TH clearance.…”

Thyroid Hormone Supplementation in Sepsis: An Experimental Study

“…44 Iodine in the thyroid hormones is also thought to be associated with the MPO-H 2 O 2 -halide system, and the serum DIT levels increased in patients with a severe infection because of the use of iodine in the phagocytic system. The levels of the thyroid hormones were found to increase in the serum of patients with sepsis as compared to other diseases.…”

Characterization of T4-Binding Globulin Cleaved by Human Leukocyte Elastase

“…There was no such localized T 4 uptake in patients who had received antibiotics for more than a week or did not have clinical signs of bacterial infection. Furthermore, Meinhold et al (43) have shown that T 4 is degraded to diiodotyrosine (DIT) in phagocytosing and therefore activated leukocytes in patients with severe infections or sepsis. DIT and its metabolites are bactericidal (44).…”