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Mitsuru Ito, Nagaoki Toyoda, Emiko Nomura, Yuuki Takamura, Nobuyuki Amino, Toshiji Iwasaka, Junta Takamatsu, Akira Miyauchi, and Mitsushige Nishikawa

Objective

3,5,3′-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 (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 T3-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 T3-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 T3-P-GD and CT-GD and the serum FT3-to-FT4 ratio (r=0.370, P<0.05). Moreover, there was a strong correlation between the thyroidal D2 activity in those patients and the serum FT3-to-FT4 ratio (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 FT3-to-FT4 ratio in T3-P-GD.

Free access

Mitsuru Ito, Akira Miyauchi, Shinji Morita, Takumi Kudo, Eijun Nishihara, Minoru Kihara, Yuuki Takamura, Yasuhiro Ito, Kaoru Kobayashi, Akihiro Miya, Sumihisa Kubota, and Nobuyuki Amino

Objective

Thyroidal production of triiodothyronine (T3) is absent in patients who have undergone total thyroidectomy. Therefore, relative T3 deficiency may occur during postoperative levothyroxine (l-T4) therapy. The objective of this study was to evaluate how the individual serum T3 level changes between preoperative native thyroid function and postoperative l-T4 therapy.

Methods

We retrospectively studied 135 consecutive patients with papillary thyroid carcinoma, who underwent total thyroidectomy. Serum free T4 (FT4), free T3 (FT3), and TSH levels measured preoperatively were compared with those levels measured on postoperative l-T4 therapy.

Results

Serum TSH levels during postoperative l-T4 therapy were significantly decreased compared with native TSH levels (P<0.001). Serum FT4 levels were significantly increased (P<0.001). Serum FT3 levels were significantly decreased (P=0.029). We divided the patients into four groups according to postoperative serum TSH levels: strongly suppressed (less than one-tenth of the lower limit); moderately suppressed (between one-tenth of the lower limit and the lower limit); normal limit; and more than upper limit. Patients with strongly suppressed TSH levels had serum FT3 levels significantly higher than the native levels (P<0.001). Patients with moderately suppressed TSH levels had serum FT3 levels equivalent to the native levels (P=0.51), and patients with normal TSH levels had significantly lower serum FT3 levels (P<0.001).

Conclusions

Serum FT3 levels during postoperative l-T4 therapy were equivalent to the preoperative levels in patients with moderately suppressed TSH levels. Our study indicated that a moderately TSH-suppressive dose of l-T4 is required to achieve the preoperative native serum T3 levels in postoperative l-T4 therapy.