Thyroglobulin Gene Mutations Producing Defective Intracellular Transport of Thyroglobulin Are Associated with Increased Thyroidal Type 2 Iodothyronine Deiodinase Activity

Kanou, Yasuhiko; Hishinuma, Akira; Tsunekawa, Katsuhiko; Seki, Koji; Mizuno, Yutaka; Fujisawa, Haruki; Imai, Tsuneo; Miura, Yoshitaka; Nagasaka, Tetsuro; Yamada, Chizumi; Ieiri, Tamio; Murakami, Masami; Murata, Yoshiharu

doi:10.1210/jc.2006-1242

Cited by 54 publications

(50 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is likely that the large goiter size is related to stimulation by higher TRAb in the patients with T 3 -P-GD. Interestingly, higher thyroidal D2 activities have been observed in some large goitrous thyroid diseases such as TG gene mutations or McCune-Albright syndrome (9,10). These findings suggest that a large goiter itself or any stimulating factor(s) that enlarge the thyroid volume may induce higher thyroidal D2 activity in the patients with T 3 -P-GD.…”

Section: Discussionmentioning

confidence: 92%

“…On the other hand, Laurberg et al (6) estimated by an indirect method using propylthiouracil (PTU) that D1-generated T 3 in the thyroid gland is the major source of plasma T 3 in hyperthyroid humans. Recently, some cases of relatively high serum T 3 levels were reported in patients with follicular thyroid carcinoma (7), GD during PTU treatment (8), thyroglobulin (Tg) gene mutations (9), and McCuneAlbright syndrome (10). In these cases, D2 activity in the thyroid tissues was increased, and the T 4 to T 3 conversion catalyzed by D2 was assumed to be responsible for the T 3 toxicosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Toyoda²,

Nomura³

et al. 2011

European Journal of Endocrinology

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

Toyoda²,

Nomura³

et al. 2011

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

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

Miyauchi

Kang

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: We and others recently reported that in total thyroidectomy (TT), serum triiodothyronine (T 3 ) levels during levothyroxine (L-T 4 ) therapy were low compared to the preoperative levels, suggesting that the presence of the thyroid tissue affects the balances of serum thyroid hormone levels. However, the effects of remnant thyroid tissue on these balances in thyroidectomized patients have not been established. Methods: We retrospectively studied 253 euthyroid patients with papillary thyroid carcinoma who underwent a TT or hemithyroidectomy (HT). We divided the cases into the TTCsupplemental L-T 4 (CL-T 4 ) group (nZ103); the HTCL-T 4 group (nZ56); and the HT-alone group (nZ94). We compared the postoperative serum levels of free T 4 (FT 4 ) and free T 3 (FT 3 ) and the FT 3 /FT 4 ratio in individual patients with those of controls matched by serum TSH levels. Results: The TTCL-T 4 group had significantly higher FT 4 (P!0.001), lower FT 3 (P!0.01) and lower FT 3 /FT 4 (P!0.001) levels compared to the controls. The HTCL-T 4 group had FT 4 , FT 3 and FT 3 /FT 4 levels equivalent to those of the controls. The HT-alone group had significantly lower FT 4 (P!0.01), equivalent FT 3 (PZ0.083), and significantly higher FT 3 /FT 4 (P!0.001) ratios than the controls. Conclusions: The presence of the remnant thyroid tissue was associated with different thyroid hormone balances in thyroidectomized patients, suggesting that T 3 production by remnant thyroid tissue has a substantial effect on the maintenance of postoperative serum T 3 levels.

show abstract

“…Fifty-two mutations have been identified and characterized in the human TG: 11 splice site mutations, 11 nonsense mutations, 23 missense mutations, 6 deletions (5 single and 1 involving a large number of nucleotides) and 1 single nucleotide insertion [10,11,12,13,14,15,17,30,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58] (table 1; fig. 2, 3).…”

Section: Tg Mutations and Congenital Hypothyroidismmentioning

confidence: 99%

“…Sequencing analysis of the TG gene revealed 9 missense mutations that involved wild-type cysteine residue: p.C164Y [48], p.C175G [30], p.C1058R [13,30], p.C1245R [13,30,40,50], p.C1588F [30], p.C1878Y [30,47], p.C1977S [13,30,40], p.C1987Y [30] and p.C2135Y [30] (table 1). The loss of cysteine residues can eliminate disulfide bonds and alter the normal conformational structure of the TG, consequently preventing the interaction of acceptor and donor hormonogenic sites.…”

Section: Tg Mutations and Congenital Hypothyroidismmentioning

confidence: 99%

Thyroglobulin Gene Mutations in Congenital Hypothyroidism

Targovnik

Citterio

Rivolta³

2011

Horm Res Paediatr

View full text Add to dashboard Cite

Human thyroglobulin (TG) gene is a single copy gene, 270 kb long, that maps on chromosome 8q24.2–8q24.3 and contains an 8.5-kb coding sequence divided into 48 exons. TG is exclusively synthesized in the thyroid gland and represents a highly specialized homodimeric glycoprotein for thyroid hormone biosynthesis. Mutations in the TG gene lead to permanent congenital hypothyroidism. The presence of low TG level and also normal perchlorate discharge test in a goitrous individual suggest a TG gene defect. Until now, 52 mutations have been identified and characterized in the human TG gene with functional impact such as structural changes in the protein that alter the normal protein folding, assembly and biosynthesis of thyroid hormones. 11 of the mutations affect splicing sites, 11 produce premature stop codons, 23 lead to amino acid changes, 6 deletions (5 single and 1 involving a large number of nucleotides) and 1 single nucleotide insertion. TG mutations are inherited in an autosomal recessive manner and affected individuals are either homozygous or compound heterozygous. The p.R277X, p.C1058R, p.C1977S, p.R1511X, p.A2215D and p.R2223H mutations are the most frequently identified TG mutations. This mini-review focuses on genetic and clinical aspects of TG gene defects.

show abstract

Thyroglobulin Gene Mutations Producing Defective Intracellular Transport of Thyroglobulin Are Associated with Increased Thyroidal Type 2 Iodothyronine Deiodinase Activity

Cited by 54 publications

References 31 publications

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

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

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

Thyroglobulin Gene Mutations in Congenital Hypothyroidism

Contact Info

Product

Resources

About