Thyroid disease with monoclonal (immunoglobulin G lambda) antibody to triiodothyronine and thyroxine

A man with previous Graves' disease spontaneously developed hypothyroidism. He became euthyroid with T4 therapy, but developed inappropriately elevated serum levels of T3 and, to a lesser extent, T4. Gel filtration analysis (Sephadex G-150) of serum trace-labeled with [125I]T3 revealed binding to a high molecular weight fraction, distinct from normal T3-binding proteins. This abnormal activity cochromatographed with serum immunoglobulin G (IgG) by DEAE-cellulose chromatography and gel filtration, and was retained by the F(ab)2 fragment of IgG, indicating its true antibody nature. By isoelectric focussing, there was restricted heterogeneity of the [125I]T3-antibody complex (pI 9.0-9.1), and the antibody was identified as an IgG (lambda) monoclonal Ig by immune precipitation. Antigenic cross-reactivity with T4 was demonstrated by inhibition of hapten binding. The affinity of the antibody for T3 was high (Ka = 0.9 x 10(9) liter mol-1), and the T3 binding capacity of the antibody in serum was estimated as 1132 ng/dl, equivalent to 1.39 mg T3-specific IgG/liter (0.014% of the total serum IgG). This binding capacity was similar to the serum T3 values (1100-1300 ng/dl) at which transition from hypothyroid to euthyroid states was observed, as judged by clinical examination and measurement of serum TSH levels.