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Purpose: The serum free triiodothyronine (FT 3 )/free thyroxine (FT 4 ) ratio in patients with huge goitrous Hashimoto's thyroiditis (HG-HT) is relatively high. We investigated the cause of high FT 3 /FT 4 ratios., Methods: We measured the serum FT 3 , FT 4 , and thyrotropin (TSH) levels of seven patients with HG-HT who had undergone a total thyroidectomy. Eleven patients with papillary thyroid carcinoma served as controls. The activities and mRNA levels of type 1 and type 2 iodothyronine deiodinases (D1 and D2, respectively) were measured in the thyroid tissues of HG-HT and perinodular thyroid tissues of papillary thyroid carcinoma., Results: The TSH levels in the HG-HT group were not significantly different from those of the controls. The FT 4 levels in the HG-HT group were significantly lower than those of the controls, whereas the FT 3 levels and FT 3 /FT 4 ratios were significantly higher in the HG-HT group. The FT 3 /FT 4 ratios in the HG-HT group who had undergone total thyroidectomy and received levothyroxine therapy decreased significantly to normal values. Both the D1 and D2 activities in the thyroid tissues of the HG-HT patients were significantly higher than those of the controls. However, the mRNA levels of both D1 and D2 in the HG-HT patients' thyroid tissues were comparable to those of the controls. Interestingly, there were significant correlations between the HG-HT patients' D1 and D2 activities, and their thyroid gland volume or their FT 3 /FT 4 ratios., Conclusions: Our results indicate that increased thyroidal D1 and D2 activities may be responsible for the higher serum FT 3 /FT 4 ratio in patients with HG-HT.

Objective: 3,5,3'-triiodothyronine-predominant Graves' disease (T(3)-P-GD) is characterized by a persistently high serum T(3) level and normal or even lower serum thyroxine (T(4)) level during antithyroid drug therapy. The source of this high serum T(3) 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 T(3) level in T(3)-P-GD., Methods: We measured the activity and mRNA level of both D1 and D2 in the thyroid tissues of patients with T(3)-P-GD (n=13) and common-type GD (CT-GD) (n=18) who had been treated with methimazole up until thyroidectomy., Results: Thyroidal D1 activity in patients with T(3)-P-GD (492.7±201.3 pmol/mg prot per h) was significantly higher (P<0.05) than that in patients with CT-GD (320.7±151.9 pmol/mg prot per h). On the other hand, thyroidal D2 activity in patients with T(3)-P-GD (823.9±596.4 fmol/mg prot per h) was markedly higher (P<0.005) than that in patients with CT-GD (194.8±131.6 fmol/mg prot per h). There was a significant correlation between the thyroidal D1 activity in patients with T(3)-P-GD and CT-GD and the serum FT(3)-to-FT(4) ratio (r=0.370, P<0.05). Moreover, there was a strong correlation between the thyroidal D2 activity in those patients and the serum FT(3)-to-FT(4) ratio (r=0.676, 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 FT(3)-to-FT(4) ratio in T(3)-P-GD.