Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant syndrome caused by abnormal albumin with an increased affinity for thyroxine (T4). Two types of mutations in the albumin gene, replacing the normal arginine 218 with a histidine (R218H) or a proline (R218P), have been reported to cause FDH. Here, we report a pregnant Japanese woman with FDH caused by the mutant albumin R218P. She had extremely elevated total T4 levels but normal TSH. While the majority of T4 was bound to albumin, T4 binding to thyroxine-binding globulin (TBG) was progressively increased throughout pregnancy. Her infant also had elevated serum T4 but normal thyrotropin (TSH). The presence of a guanine to cytosine transition in the second nucleotide of codon 218 of the albumin gene, resulting in a substitution of proline for the normal arginine (R218P), was revealed in the proband. Serum free thyroxine (FT4) levels were increased when measured with some commercial kits including equilibrium dialysis followed by radioimmunoassay (RIA) but not when determined by RIA after ultrafiltration of sera. These results indicate an increased T 4 binding to TBG during pregnancy in the patients with FDH. Furthermore, our results suggest that normal serum FT4 determined by equilibrium dialysis is not an ultimate standard for the diagnosis of FDH in the patients with the mutant albumin R218P.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism