Thyroxine-Binding Globulin Concentrations

Plasma thyroid hormone concentrations may be abnormal in non-thyroid disease and pose diagnostic problems. For example, concentrations of triiodothyronine (T3) in the blood decline in acute illness with a reciprocal increase in reverse triiodothyronine (reverse T3), but thyroxine (T4) concentrations are usually normal or only slightly decreased (1, 2). However, McLarty et al. (3) reported that in severely ill patients T4, as well as T:t, values may decrease progressively. Because of the parallel changes in the free T4 and T:t indices, they believed that this could not be explained by changes in thyroid hormone-binding proteins. We have noted similar low serum T4 concentrations in severely ill patients but have found significant decreases in the concentration of thyroxine-binding globulin (TBG). We studied two groups of patients from the Intensive Therapy Unit. The first group (fatalities) consisted of eleven who died as a result of a severe illness of recent onset. There were six with cardiac and (or) respiratory failure, four with severe infection, and one with severe trauma. The second group (survivors) consisted of eleven consecutive patients with similar problems, who responded to therapy: four with cardiac and (or) respiratory failure, two with severe infection, two with trauma, and three severe drug-overdose patients. We compared results from the blood samples obtained on admission for both groups and from the preterminal sample (within 24 h of death) for the fatalities. Using sera submitted for routine biochemistry, we measured T4 by radioimmunoassay (with polyethylene glycol precipitation), TBG by radioimmunoassay with CIS reagents (TBGK-1), and T3 by Sephadex uptake (T:tSU) (4). From these values we calculated both a free thyroxine index (FTI), by the formula T4 X T3SU/iOO, and the T4/TBG ratio. Figure 1 shows that, although many TBG values were within the overall reference interval (12-29 mg/L), the concentrations are significantly lower (and T3SU values significantly higher) in those who died than in those who survived. This is already apparent on admission: only four patients had TBG values similar to those who survived. In three, the values decreased before death; the changes, and the intervals between the admission and preterminal samples, were 13, ii, and 6 mg/L in two, seven, p