Triiodothyronine, Thyroxine, and Iodine in Purified Thyroglobulin from Patients with Graves' Disease

Abstract

Previous studies have suggested that there is an overproduction of triiodothyronine (T₃) relative to thyroxine (T₄) in patients with thyrotoxicosis associated with Graves' disease. To evaluate whether or not an increased ratio of T₃ to T₄ in thyroidal secretion could be contributing to this relative T₃ hyperproduction, T₃, T₄, and iodine were measured in thyroglobulin (Tg) from controls and patients with Graves' disease who had been treated either with propranolol only or with antithyroid drugs plus iodide before surgery. To avoid possible artifacts associated with pulse labeling and chromatography, T₃ and T₄ were determined by radioimmunoassay of Pronase hydrolysates of purified Tg. Results of analyses of Tg from six control patients and seven with Graves' disease, not receiving thiourea drugs or iodide, showed that the iodine content of Graves' disease Tg was not different from normal. Both contained 3.4 residues of T₄/molecule Tg, but there was 0.39±0.08 (mean±SD) residue of T₃/molecule Tg in Graves' Tg as opposed to 0.23±0.07 residue T₃ molecule Tg in controls matched for iodine content (P < 0.01). This difference resulted in a significantly lower T₄/T₃ molar ratio (9±2) in Graves' Tg as opposed to control (15±2, P < 0.001). In Tg from patients with treated Graves' disease, iodine, T₃, and T₄ were reduced, but the reduction in the latter was more substantial, resulting in a T₄/T₃ molar ratio of 3.4±1. Fractionation of Tg from all groups by RbCl density gradient ultracentrifugation indicated that at physiological levels of Tg iodination, the molar ratio of T₃/Tg was consistently higher in Graves' disease. The specific mechanism for this difference is not known, but it is not due to iodine deficiency. If T₃ and T₄ are secreted in this altered ratio in patients with Graves' disease, the magnitude of the difference could explain the relative T₃ hyperproduction which is characteristic of this state.