A new type of albumin with predominantly increased binding affinity for 3,3′, 5-triiodothyronine in a patient with Graves’ disease

Abstract

A new type of serum albumin, that shows a markedly enhanced binding activity for 3,3′, 5-triiodothyronine (T₃), a somewhat increased activity for thyroxine (T₄), and a normal activity for 3, 3′, 5-triiodothyronine (rT₃) is described. This albumin was found in a patient with Graves’ disease. After successful subtotal thyroidectomy, the existence of abnormal binding activity for T₃ was suspected in this patient because of persistently increased total T₃ concentrations in spite of elevated thyrotropin levels. Although free T₃ and T₄ concentrations measured by radioimmunoassay using commercial tracer analogue kits were markedly increased, those measured by equilibrium dialysis were within normal ranges. Electrophoretic studies revealed that these abnormalities were due to the markedly increased T₃ binding activity by the serum albumin; that for T₄ was also slightly increased. Scatchard plot analysis revealed that the association constant (Ka) for T₃ of the patient’s albumin was 5.1 × 10⁶/M (normal pooled albumin; 6.2 × 10⁵/M), and those for T₄ and rT₃ were 5.2 × 10⁶/M and 2.7 × 10⁶/M, respectively (normal pooled albumin; 2.1 × 10⁶/M for both T₄ and rT₃). The increased binding of albumin to T₃ and T₄ was markedly inhibited by barbitone, and 8-anilino-1-naphthalenesulfonic acid. These characteristic features, and erroneously high values of free T₃ and T₄ concentrations measured by tracer analogue kits were similar to those seen in patients with familial dysalbuminemic hyperthyroxinemia, which have been previously reported. These findings strongly suggest that this albumin is a new variant in various dysalbuminemic syndromes, and the abnormal binding of iodothyronines moieties in these syndromes are not biochemically identical.