Inhibition of serum protein binding of thyroxine in a hypothyroid patient with familial dysalbuminemic hyperthyroxinemia

Abstract

Objective: To investigate unusual free thyroxine (FT 4) responses to T 4 replacement doses in a hypothyroid patient with familial dysalbuminemic hyperthyroxinemia (FDH). Methods: In this FDH hypothyroid patient, serum FT 4 concentration by equilibrium dialysis and T 4, triiodothyronine (T 3), and thyroid stimulating hormone (TSH) determinations were supplemented by thyroxine binding globulin (TBG) and thyroxine binding prealbumin (TBPA) measurements. Results: Initial thyroid function tests were compatible with hypothyroidism and FDH (T 4 = 78 nmol/L, T 3 = 1.08 nmol/L, FT 4 = 11.6 pmol/L, TSH = 45 mU/L). When she was initially treated with T 4 (0.112-0.088 mg/day) there was an increase in FT 4 concentration to hyperthyroid levels accompanied by TSH inhibition (FT 4 = 31–51 pmol/L, TSH = <0.03 mU/L); the patient also complained of intolerance and nervousness, and T 4 treatment was discontinued. Concentrations of thyroxine binding globulin (TBG) and thyroxine binding prealbumin (TBPA) were normal. When T 4 therapy was later resumed at a dosage of 0.075 mg/day, there was a marked increase in percent dialyzable T 4. The elevation in percent dialyzable T 4 during T 4 replacement in a patient with FDH is unusual in view of the very large T 4 binding capacity of FDH albumin. The presence of an inhibitor that reduced T 4 binding by both TBG and FDH albumin probably explains the elevation in percent dialyzable T 4 during T 4 treatment. Conclusion: This FDH patient represents the first case of a putative inhibitor of T 4 binding to both TBG and FDH albumin. The inhibition of T 4 binding by these disparate proteins suggests that the inhibitor effect is mediated nonspecifically.