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

Abstract

Objective: 3,5,3 0 -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 (nZ13) and common-type GD (CT-GD) (nZ18) who had been treated with methimazole up until thyroidectomy. Results: Thyroidal D1 activity in patients with T 3 -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 T 3 -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 T 3 -P-GD and CT-GD and the serum FT 3 -to-FT 4 ratio (rZ0.370, 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 (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 FT 3 -to-FT 4 ratio in T 3 -P-GD.European Journal of Endocrinology 164 95-100

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

“…Independently of the genesis of the hyperthyroidism, PTU resulted in a reduction of the T4-to-T3 conversion to 47% of the initial value, while adding sodium ipodate caused a further decrease in the ratio to 34 % of the initial value. These results suggest that the major source of the excess T3 was D1-mediated T4 monodeiodination (50%), with a minor role for D2 (15-20%) (78,79).…”

Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients

“…Maia et al (16) reported that D2 is expressed in the human thyroid gland and is postulated to play an important role as a source of plasma T 3 . As a matter of fact, it has been suggested that the increased D2 in the thyroid gland may account for the status of a low FT 4 with relatively high or normal circulating T 3 levels in other thyroid diseases, such as follicular carcinoma (10), thyroglobulin gene abnormalities (17), and T 3 -predominant Graves' disease (18). Very recently, Hoermann et al reported the association between thyroid volume and deiodinase activity.…”

Fetal cell carcinogenesis of the thyroid: A modified theory based on recent evidence [My Opinion]

“…Some recent studies reported an interesting similarity in gene expression between tissues from T 3 predominant Graves' disease and hyperfunctioning adenomas. They overexpress not only iodothyronine deiodinases but also N-cadherin (CDH2) [54,55]. If T 3 predominant Graves' disease is caused by an increased number of fetal thyroid cells, probably prothyrocytes, some clinical features of T 3 -predominant Graves' disease, such as its high prevalence in the young and tendency to form a large goiter, are easily explained.…”