Thyroxin binding by human serum albumin after denaturation of the thyroxin-binding globulin in familial dysalbuminemic hyprethyroxinemia

Abstract

Abnormal binding of thyroxin (T4) to serum albumin of subjects with familial dysalbuminemic hyperthyroxemia (FDH) is generally demonstrated by the T4-loaded charcoal uptake test, with T4 added in excess (0.1 mmol/L) to accentuate T4 binding to albumin in FDH. I describe a binding study involving T4 tracer in which thyroxin-binding globulin is denatured in samples by treatment with mild acid at pH < 3.0. The tracer is bound to the serum albumin and, to a greater extent, to the FDH albumin, because the binding by thyroxin-binding prealbumin is blocked by barbital buffer. The result of the [125I]T4 binding to the albumin is expressed as a T4 binding index, based on results for pooled sera from patients with normal thyroid function as a reference. The mean index in FDH was 4.08 (SD 0.92, n = 5); in hypoalbuminemia, 0.66 (SD 0.18, n = 8); in normal subjects, 1.00 (SD 0.11, n = 20). This albumin-binding index enables the rapid and unequivocal diagnosis of subjects with FDH, without the addition of unlabeled T4.