Graves' Disease Associated with Familial Deficiency of Thyroxine-Binding Globulin

Abstract

Five patients presented with symptoms of Graves' disease and a marked decrease in their thyroxine-binding globulin (TBG) capacity. While thyrotoxic, mean values ±SD for the 5 patients were: total thyroxine (TT₄) 8.8±2.0 μg/100 ml (normal range 4.4–9.3); TBG capacity 6.1±1.1 /g T₄/100 ml (normal range 16–24); free thyroxine index (FTI) 25.3±8.9 (normal range 3.6–9.3); and total triiodothyronine (TT₃) 244±56 ng/100 ml (normal range 80–160). When euthyroid, both TT₄ (2.8±0.8 /g/ 100 ml) and TT₃ (68±12 ng/100 ml) were below the normal range and FTI (5.8±0.6) was normal. All patients were male, and family studies revealed decreased TBG capacity in blood relatives consistent with X-chromosome linked inheritance. All examined relatives of the propositi, whether hemizygous or heterozygous, were euthyroid. Over the same period of time 7 additional patients (excluding family members of propositi) were found to be euthyroid but had decreased TBG capacity. The occurrence of thyrotoxicosis in 5 out of 12 patients with inherited TBG deficiency suggests an association rather than a coincidental finding, although initial tests were performed because of suspected thyroid dysfunction. The incidence of thyrotoxicosis in patients with inherited TBG deficiency is also high on the basis of the reported prevalence of the latter genetic abnormality. This study stresses the importance of determining TT₃ and FTI on patients who are clinically thyrotoxic but have normal TT₄.