Relationship of T-uptake and thyroxine in hypo- and hyperthyroid patients.

Radioimmunoasaay is an accurate and direct method for assessing thyroxine (T4)-binding globulin concentrations. Because such techniques are costly, time consuming, and use radioactive materials, nonisotopic assays are often favored. Although it is an indirect measure of T4 binding protein CFBP) concentration, resin triiodothyronine uptake (RT3U) has been the most widely used test, to date, for this assessment However, RT3U is heavily influenced by the total T4 concentration in the specimen. RT3U and total P4 are expected to change proportionately (but not linearly) when TBP concentrations are within the reference range (1). Hyperthyroid patients are expected to have normal to high RT3U concentrations, whereas the converse is expected in hypothyroid patients. To automate thyroid hormone testing on a single instrument, many laboratories measure T-uptake on the Abbott IM analyzer (Abbott Park, IL), replacing the RT3U assay. In the fluorescence polarization immunoassay (IM,., method) for P-uptake, fluerescein-labeled P4 is added to the patient’s serum and equilibrates between the TBP-bound and free fractions. As a result, T-uptake is directly proportional to the concentration of TBP. According to the AbbOtt IM T-upt.ake test product insert, a reciprocal relation between RT3U and T-uptake is anticipated: transformed % uptake = mean normal range/t0.8 (T-uptake)2 + 0.2]. To investigate the effects of hyperand hypothyroidism on P-uptake values, we reviewed 1766 consecutive thyroid profiles performed in our clinical laboratory over a three-month period. AU assayswere performed on the IM,, analyzer [reference ranges for thyrotropin (TSH) = 0.1-5.0 mllJ/L and P4 = 45-120 tg/L]. Biochemically hyperthyroid subjects were identified as patients with concentrations of TSH <0.1 mllJ/L and T4 >120 tg/L (n = 30, 1.7% of all thyroid panels studied). Biochemically hypothyroid subjects were defined as patients with concentrations of TSH >5.0 mIUIL and T4 <45 g/L (n 43, 2.4% of all thyroid panels studied). Linear correlations were sought between P-uptake and T4. Within each patient group, P-uptake was inversely proportional to T4 (in the hyperthyroid group, r = 0.79, P = <0.00001; in the hypothyroid group, r = 0.32, P = 0.04), whereas the majority of individual P-uptake results fell within the reference range (Figure 1). The P-uptake assay is performed with approximately a 50-fold excess of fluorescein-labeled P4 tracer, therefore, changes in the absolute P4 concentration should have a negligible analytical effect. We surmise that the inverse relation between P-uptake and T4 probably reflects the metabolic effects of thyroid hormone on PBP concentrations either through changes in PBP production or as a result of degradation. These findings are consistent with a study by Ahmed and Smethurst (2), in which PBG concentrations were essentially inversely proportional to the total P4. Analogous results were reported by Ishida et al. (3) regarding concentrations of thyroxine-binding prealbumin in various thyroidal conditions. Together, these data predict that as TBP concentrations decrease with increasing T4 concentrations, the proportion of unbound P4 will rise more rapidly than the increase in total T4. The inverse effect would apply for decreases in T4 concentrations in hypothyroidism as well. Medical practitioners should be aware of the metabolic effects of thyroid hormones on TBP concentrations in the management of patients with thyroid dysfunction.