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

OBJECTIVE

To investigate unusual free thyroxine (FT4) responses to T4 replacement doses in a hypothyroid patient with familial dysalbuminemic hyperthyroxinemia (FDH).

METHODS

In this FDH hypothyroid patient, serum FT4 concentration by equilibrium dialysis and T4, triiodothyronine (T3), 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 (T4 = 78 nmol/L, T3 = 1.08 nmol/L, FT4 = 11.6 pmol/L, TSH = 45 mU/L). When she was initially treated with T4 (0.112-0.088 mg/day) there was an increase in FT4 concentration to hyperthyroid levels accompanied by TSH inhibition (FT4 = 31-51 pmol/L, TSH = <0.03 mU/L); the patient also complained of intolerance and nervousness, and T4 treatment was discontinued. Concentrations of thyroxine binding globulin (TBG) and thyroxine binding prealbumin (TBPA) were normal. When T4 therapy was later resumed at a dosage of 0.075 mg/day, there was a marked increase in percent dialyzable T4. The elevation in percent dialyzable T4 during T4 replacement in a patient with FDH is unusual in view of the very large T4 binding capacity of FDH albumin. The presence of an inhibitor that reduced T4 binding by both TBG and FDH albumin probably explains the elevation in percent dialyzable T4 during T4 treatment.

CONCLUSIONS

This FDH patient represents the first case of a putative inhibitor of T4 binding to both TBG and FDH albumin. The inhibition of T4 binding by these disparate proteins suggests that the inhibitor effect is mediated nonspecifically.