Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with 3,5,3′-triiodothyronine-predominant Graves' disease

Objective: 3,5,3 0 -triiodothyronine-predominant Graves’ disease (T3-P-GD) is characterized by a persistently high serum T3 level and normal or even lower serum thyroxine (T4) level during antithyroid drug therapy. The source of this high serum T3 level has not been clarified. Our objective was to evaluate the contribution of type 1 and type 2 iodothyronine deiodinase (D1 (or DIO1) and D2 (or DIO2) respectively) in the thyroid gland to the high serum T3 level in T3-P-GD. Methods: We measured the activity and mRNA level of both D1 and D2 in the thyroid tissues of patients with T3-P-GD (nZ13) and common-type GD (CT-GD) (nZ18) who had been treated with methimazole up until thyroidectomy. Results: Thyroidal D1 activity in patients with T3-P-GD (492.7G201.3 pmol/mg prot per h) was significantly higher (P!0.05) than that in patients with CT-GD (320.7G151.9 pmol/mg prot per h). On the other hand, thyroidal D2 activity in patients with T3-P-GD (823.9G596.4 fmol/mg prot per h) was markedly higher (P!0.005) than that in patients with CT-GD (194.8G131.6 fmol/mg prot per h). There was a significant correlation between the thyroidal D1 activity in patients with T3-PGD and CT-GD and the serum FT3-to-FT4 ratio (rZ0.370, P!0.05). Moreover, there was a strong correlation between the thyroidal D2 activity in those patients and the serum FT3-to-FT4 ratio (rZ0.676, P!0.001). Conclusions: Our results suggest that the increment of thyroidal deiodinase activity, namely D1 and especially D2 activities, may be responsible for the higher serum FT3-to-FT4 ratio in T3-P-GD.