Abnormal thyroid function tests in severe non-thyroidal illness: diagnostic and pathophysiologic aspects

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Abstract
In vitro thyroid function tests were studied in twenty-three patients with serious non-thyroidal illness. All had reduced protein binding of serum thyroxine (T4) and serum triiodothyronine (T3) as reflected in increased T4 and T3 uptake tests. The mean T4-binding prealbumin (TBPA) capacity and concentration were about one third the normal levels, whereas the decrease in T4-binding globulin (TBG) was much smaller. Increased serum free fatty acids and reverse T3 were frequently observed, but in vitro displacement of thyroid hormones from their binding sites was achieved only with much higher concentrations of these compounds. Other still unrecognized substances significantly inhibiting binding of thyroid hormones might, however, occur in sera of severely ill patients. Evidence in favour of this possibility was the disproportionately high serum T4 by TBG-binding assay relative to T4 by radioimmunoassay. In most of the patients the dual-stage free T4 was elevated, whereas the single-stage free T4 index (CT4I) was within the reference interval. However, neither of these indices reflected the moderately increased dialysable free T4 concentration very accurately. The free T3 index was depressed in most of the patients, whereas the dialysable free T3 concentration was not affected. For practical purposes the combination of normal serum T4 and CT4I in a severely ill patient indicates absence of an associated thyrometabolic disorder.