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Triiodothyronine (T₃)-Binding Immunoglobulins in a Euthyroid Woman: Effects on Measurement of T₃ (RIA) and on T₃ Turnover

The Robert H. Williams Laboratory for Clinical Research, Harborview Medical Center Seattle, Washington
Department of Medicine, University of Washington School of Medicine Seattle, Washington

A 36-year-old woman with nodular goiter, nervousness, and tachycardia was evaluated for T₃ toxicosis. Her serum thyroxine level, resin T₃ uptake, and thyroidal radioiodine uptake were normal. Her T₃, (RIA), by a technique employing charcoal to separate bound and free T₃, was reported as indeterminate due to an interfering substance; by a double-antibody method, her T₃ (RIA) was 325 ng/dl. Further studies of the patient's serum revealed an abnormal T₃-binding protein which migrated in the beta-gamma globulin zone on paper electrophoresis and gel filtration chromatography (Sephadex G-200), and was precipitated from serum by rabbit anti-human Fab antibody. The gamma globulin fraction of the patient's serum, separated by a standard technique, showed strong binding activity toward [¹²⁵I]T₃, with an association constant of 4.1 x 10⁸ l/mole (Scatchard plot). In a similar system, labeled T₄ was not bound.

To avoid artefacts which this T₃-binding protein might produce in assaying unextracted serum, T₃ (RIA) was performed on an ethanol extract of serum and found to be 191 ng/dl, a slight elevation. However, the metabolic clearance rate of injected [¹²⁵I]T₃, estimated by non-compartmental analysis of the serum decay curve or by the specific activity of urinary T₃, was about 16 l/day, a low value, so that the T₃ production rate, 31 µg/day, was normal. The patient's symptoms disappeared with the resolution of domestic problems, and she appeared clinically euthyroid. Serum TSH was 5.0 uU/ml and antithyroglobulin titer, 1:16. A test for antibodies to thyroid microsomes was negative.

We postulate that this subject was euthyroid, but had a concentration of T₃-binding immunoglobulin which was sufficient to produce modest slowing of T₃ turnover, borderline elevation of extractable T₃ (RIA), and a major artefact in the T₃ (RIA) measurement of unextracted serum. A similar abnormality may account for other instances of. high T₃:T₄ ratios in serum.

Received July 7, 1975.

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