Immunoglobulin binding of thyroid hormones in a case of Waldenstrom's macroglobulinemia

This paper describes a case of hypothyroidism in a patient with Waldenström's disease in which the evidence of thyroid failure was accompanied by an abnormal binding of thyroid hormones in the gamma-globulin fraction. A 68-yr-old patient with Waldenström's disease appeared to be hypothyroid by clinical and laboratory criteria. Serum TSH was elevated; serum T3 (measured by RIA) was low, while T4 levels were undetectable or very high according to the method used. Serum free thyroid hormones were in the hypothyroid range, and both antithyroglobulin and antimicrosomal thyroid antibodies were undetectable. The thyroid gland was normal at autopsy. Elevated binding of radiolabeled thyroid hormones by the patient's serum gamma-globulins was demonstrated by reverse flow electrophoresis and cellulose acetate electrophoresis. This binding could be inhibited by preincubation of serum samples with unlabeled T4 and T3, but not with human thyroglobulin, rT3, DIT, or MIT. Immunoprecipitation of the patient's serum incubated with [125I]T4 or [125I]T3 showed that 56% of T4 and 30% of T3, respectively, were precipitated using an antihuman immunoglobulin M(IGM) serum; only [125I]T4 was precipitable (22%) by the addition of an antihuman immunoglobulin G(IgG) serum. The binding of the thyroid hormones by IgM and IgG, which reduced T4 and T3 availability for their metabolic action at the tissue level, could have contributed to the clinical picture.