Specific Methods to Identify Plasma Binding Abnormalities in Euthyroid Hyperthyroxinemia*

Abstract

Methods to identify the plasma T4-binding abnormalities that can cause euthyroid hyperthyroxinemia were evaluated in patients with excess T4-binding globulin, familial dysalbuminemic hyperthyroxinemia, prealbumin-associated hyperthyroxinemia, and autoantibody binding of T4. Familial dysalbuminemic hyperthyroxinemic serum showed a unique persistence of abnormal [125I]T4 binding when diluted 1:100 in phosphate buffer with added 1000-fold excess of unlabeled T4 (10(-6) M T4). Immunoprecipitation of [125I]T4 by antibody to prealbumin, precipitation of [125I]T4 by polyethylene glycol 6000 19%, and in vitro resin uptake of T3 were specific for prealbumin-associated hyperthyroxinemia, autoantibody binding of T4, and T4-binding globulin excess, respectively. These simple methods facilitate investigation of patients with euthyroid hyperthyroxinemia and will identify individuals and families at risk of misdiagnosis by standard methods. Use of these techniques rules out the known binding abnormalities in hyperthyroxinemic patients and may make the diagnosis of generalized hormone resistance more specific.

Laboratory and Clinical Assessment of Hyperthyroidism

“…The presence of these antibodies can be confi rmed by adding radiolabeled T4 to the patient's serum and precipitating the immunoglobulin fraction by the addition of polyethylene glycol [ 34 ].…”

Familial Dysalbuminemic Hyperthyroxinemia and Thyroid Hormone Autoantibodies: Interference in Current Free Thyroid Hormone Assays

“…Screening for FDH was performed according to Stockigt et al [2], In euthyroid FDH patient sera, out of four two-step assays, only one (GammaCoat from Incstar USA) gave reliable results in all sera, in agreement with the thyroidal status of the patients [3]. The efficacy of the washing protocol after the immunoextraction step seems to be insufficient in three other methods which gave high results in some FDH samples.…”