Circulating Thyroid Hormone Autoantibodies in a Hypothyroid Patient: Effect on Thyroxine Metabolic Clearance Rate*

Abstract

In a 53-yr-old man with hypothyroidism secondary to Hashimoto's thyroiditis, serum T4 measured by RIA was undetectable and continued to be undetectable even after T4 therapy. TSH levels also remained elevated after therapy (49μU/ml). In ethanol extracts of serum, T4 concentrations of 1.4 μg/100 ml and 5.7μg/100 ml were noted before and after T4 therapy, respectively. Based on these discrepant observations, antibodies to thyroid hormones were suspected. Electrophoretic studies of the patient's serum confirmed the presence of antibodies which bound tracer T4, T3, and rT3. Saturation studies of thyroid hormone-binding serum immunoglobulins in vitro demonstrated that only T4, antibody was specific and that it crossreacted with T3 and rT3. During T4 therapy (0.15 mg/day), antibody-binding sites were saturated by T4 as well as by peripherally generated T3 and rT3; slight binding to the antibody of [125I]T4, but not [125I]T3 or [125I]rT3, was demonstrable. The MCR of T4 in the patient while on T4 therapy was 1.02 liters/ day, which is in the normal range. The association constant of the T4 antibody was 6 × 108 M-1 and its binding capacity was 265 ng T4/ml serum. Although the T4 antibody may have blocked the access of T4 to the pituitary and thus prevented the normalization of TSH levels during therapy with T4, this and other physiological effects of the antibody are speculative. However, the T4 antibody interferes with the measurement of T4 in unextracted serum by falsely lowering the concentration when nonspecific separation methods, such as polyethylene glycol or charcoal, are used and raising the concentration when double antibody or solid phase RIA methods are used.