A new method for measuring the free thyroid hormone in human serum and an analysis of the factors that influence its concentration.

Abstract

In normal patients, the free thyroxine (T4) in serum averaged 0.050% of the total, whereas the percent of free triiodothyronine proportion was 9 to 10 times as large. Significant decreases in percent of free thyroid hormone (PFT4) were found in the serum of patients with myxedema or pregnancy and significant increases in patients with thyrotoxicosis or a variety of severe nonthyroidal illnesses (sick patients). In the several diagnostic categories, however, considerabel overlap of individual values with the normal range was observed. Values for the absolute concentration of free thyroxine in serum were decreased in patients with thyrotoxicosis. Small but significant decreases and increases, respectively, were found in absolute concentrations of free T4 in the sera of pregnant and sick patients. Use of dilute, rather than whole, serum was found to yield spuriously low values for the per cent of free T4. Enrichment of normal sera with sufficient thyroxine to bring protein-bound iodine into the thyro-toxic range increased PFT4. Nevertheless, values for the percent of free T4 in enriched specimens of normal serum were less than those usually seen in patients with thyrotoxicosis. Enrichment with thyroxine of sera in which thy roxine-binding by prealbumin (TBPA) was decreased, either as a result of systemic illness or of the addition of tetraiodothyro-acetic acid, produced far greater increases in the per cent of free T4 than it did in normal serum, and values in the thyrotoxic range resulted. The data provide further evidence that TBPA contributes significantly to thyroxine binding in normal serum and suggest that the increased values for the per cent of free T4 found in serum from thyrotoxic patients are due, at least in part, both to an increase in thyroxine concentration and a decrease in TBPA.