A NEW AND DISTINCTIVE ALBUMIN VARIANT WITH INCREASED AFFINITIES FOR BOTH TRIIODOTHYRONINES AND CAUSING HYPERTHYROXINAEMIA

Abstract

A new variant albumin with increased affinities for iodothyronines has been identified. A euthyroid woman had raised total serum concentrations of T4 (155 nmol/l), T3 (3.0 nmol/l) and rT3 (700 pmol/l) but normal levels of all three iodothyronine-binding proteins. The affinity constant for T3 binding to the albumin was substantially raised (2.2 x 10(5) l/mole; normal immeasurable), that for rT3 (1.4 x 10(6) l/mole) was increased three-fold. This new albumin binds the analogues of T4 and T3 used in Amerlex free-hormone assays more strongly than does normal albumin, resulting in erroneously elevated estimates of serum free-T4 and free-T3 by this method. The new variant albumin was indistinguishable from normal albumin in molecular size and by electrophoretic and immunological techniques. Three distinct variant albumins exhibiting differential binding of iodothyronines have now been defined: Type I causes a raised total serum T4 only; Type II produces increased total T4 and rT3; Type III (the present example) results in elevated total T4, rT3 and T3. All three variants have normal free-T4 by dialysis but spuriously raised results by the Amerlex free-T4 method. Type III also causes an artificial increase in Amerlex free-T3. The pattern of thyroid function test results in Type III can readily be confused with both hyperthyroidism and with partial peripheral resistance to thyroid hormones.