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Sources of Circulating 3,5,3'-Triiodothyronine in Hyperthyroidism Estimated after Blocking of Type 1 and Type 2 Iodothyronine Deiodinases

Departments of Endocrinology and Internal Medicine, Aalborg Hospital (P.L.), DK-9000 Aalborg, Denmark; Herlev Hospital (H.V.), DK-2730 Herlev, Denmark; Aarhus Hospital (S.N., T.S.), DK-8000 Aarhus, Denmark; Aabenraa Hospital (S.E.C.), DK-6200 Aabenraa, Denmark; Viborg Hospital (K.H.), DK-8800 Viborg, Denmark; and Hobro Hospital (K.M.P.), DK-9500 Hobro, Denmark

Address all correspondence and requests for reprints to: Peter Laurberg, M.D., Department of Endocrinology and Medicine, Aalborg Hospital, Aarhus University Hospital, DK-9000 Aalborg, Denmark. E-mail: peter.laurberg{at}rn.dk.

Context: Graves’ hyperthyroidism and multinodular toxic goiter lead to high serum T₃ compared with serum T₄. The source of this high T₃ has not been clarified.

Objective: Our objective was to assess the role of iodothyronine deiodinase type 1 (D1) and type 2 (D2) for T₃ production and to estimate the sources of T₃ in hyperthyroidism.

Design and Setting: The study was a prospective, randomized, open-labeled study in a secondary care setting.

Patients and Methods: Consecutive patients with hyperthyroidism caused by Graves’ disease or by multinodular toxic goiter were randomized to be treated with high-dose propylthiouracil (PTU) to block D1, PTU plus KI, or PTU plus sodium ipodate to additionally block D2. T₃ and T₄ were measured in serum, and we estimated the sources of T₃.

Results: PTU reduced the T₃/T₄ in serum to 47.7 ± 2.5% (mean ± SEM) of the initial value on d 4 of therapy in patients with Graves’ disease. The addition of KI to PTU led to a greater fall in T₃ and T₄, but the balance was unaltered. After PTU plus ipodate, T₃/T₄ on d 4 was lower, 34.1 ± 1.2% of the initial value. Similar variations were observed in patients with multinodular toxic goiter. Thus, the major source of the excess T₃ was D1-catalyzed T₄ deiodination, with a minor role for D2. It was estimated that the majority of this D1-catalyzed T₃ production takes place in the hyperactive thyroid gland.

Conclusion: Although thyroidal T₃ contributes only around 20% of total T₃ production in normal individuals, this is much higher in patients with a hyperactive thyroid, ranging up to two thirds. The major part is produced from T₄ deiodinated in the thyroid.

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