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Endocrine

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Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with huge goitrous Hashimoto’s thyroiditis

  • Azusa Harada
  • Emiko Nomura
  • Kumiko Nishimura
  • Mitsuru Ito
  • Hiroshi Yoshida
  • Akira Miyauchi
  • Mitsushige Nishikawa
  • Ichiro Shiojima
  • Nagaoki ToyodaEmail author
Original Article
  • 8 Downloads

Abstract

Purpose

The serum free triiodothyronine (FT3)/free thyroxine (FT4) ratio in patients with huge goitrous Hashimoto’s thyroiditis (HG-HT) is relatively high. We investigated the cause of high FT3/FT4 ratios.

Methods

We measured the serum FT3, FT4, 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 FT4 levels in the HG-HT group were significantly lower than those of the controls, whereas the FT3 levels and FT3/FT4 ratios were significantly higher in the HG-HT group. The FT3/FT4 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 FT3/FT4 ratios.

Conclusions

Our results indicate that increased thyroidal D1 and D2 activities may be responsible for the higher serum FT3/FT4 ratio in patients with HG-HT.

Keywords

Thyroid hormone metabolism Iodothyronine deiodinase Hashimoto’s thyroiditis Thyroid gland 

Notes

Acknowledgements

This study was supported by the Smoking Research Foundation of Japan Grant Number FP01606073.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee at Kuma Hospital, and all patients gave informed consent for their materials to be used and for their data to be published. This study was conducted in accordance with the principles of the Declaration of Helsinki.

References

  1. 1.
    P.R. Larsen, J.E. Silva, M.M. Kaplan, Relationships between circulating and intracellular thyroid hormones: physiological and clinical implications. Endocr. Rev. 2(1), 87–102 (1981)CrossRefGoogle Scholar
  2. 2.
    D.L. St. Germain, V.A. Galton, The deiodinase family of selenoproteins. Thyroid 7(4), 655–668 (1997)CrossRefGoogle Scholar
  3. 3.
    A.C. Bianco, D. Salvatore, B. Gereben, M.J. Berry, P.R. Larsen, Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr. Rev. 23(1), 38–89 (2002)CrossRefGoogle Scholar
  4. 4.
    G.G.J.M. Kuiper, M.H.A. Kester, R.P. Peeters, T.J. Visser, Biochemical mechanisms of thyroid hormone deiodination. Thyroid 15(8), 787–798 (2005)CrossRefGoogle Scholar
  5. 5.
    D. Salvatore, H. Tu, J.W. Harney, P.R. Larsen, Type 2 iodothyronine deiodinase is highly expressed in human thyroid. J. Clin. Invest. 98(4), 962–968 (1996)CrossRefGoogle Scholar
  6. 6.
    P. Laurberg, H. Vestergaard, S. Nielsen, S.E. Christensen, T. Seefeldt, K. Helleberg, K.M. Pedersen, Source of circulating 3,5,3’-triiodothyronine in hyperthyroidism estimated after blocking type 1 and type 2 iodothyronine deiodinses. J. Clin. Endocrinol. Metab. 92(6), 2149–2156 (2007)CrossRefGoogle Scholar
  7. 7.
    B.W. Kim, G.H. Daniels, B.J. Harrison, A. Price, J.W. Harney, P.R. Larsen, A.P. Weetman, Overexpression of type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels. J. Clin. Endocrinol. Metab. 88(2), 594–598 (2003)CrossRefGoogle Scholar
  8. 8.
    A.P. Weetman, C.A. Shepherdley, P. Mansell, C.S. Ubhi, T.J. Visser, Thyroid over-expression of type 1 and type 2 deiodinase may account for the syndrome of low thyroxine and increasing triiodothyronine during propylthiouracil treatment. Eur. J. Endocrinol. 149(5), 443–447 (2003)CrossRefGoogle Scholar
  9. 9.
    Y. Kanou, A. Hishinuma, K. Tsunekawa, K. Seki, Y. Mizuno, H. Fujisawa, T. Imai, Y. Miura, T. Nagasaka, C. Yamada, T. Ieiri, M. Murakami, Y. Murata, Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased type 2 iodothyronine deiodinase activity. J. Clin. Endocrinol. Metab. 92(4), 1451–1457 (2007)CrossRefGoogle Scholar
  10. 10.
    F.S. Celi, G. Coppotelli, A. Chidakel, M. Kelly, B.A. Brillante, T. Shawker, N. Cherman, P.P. Feuillan, M.T. Collins, The role of type 1 and type 2 5’-deiodinase in the pathophysiology of the 3,5,3’-triiodothyronine toxicosis of McCune-Albright syndrome. J. Clin. Endocrinol. Metab. 93(6), 2383–2389 (2008)CrossRefGoogle Scholar
  11. 11.
    M. Ito, N. Toyoda, E. Nomura, Y. Takamura, N. Amino, T. Iwasaka, J. Takamatsu, A. Miyauchi, M. Nishikawa, Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with 3,5,3’-triiodothyronine-predominant Graves’ disease. Eur. J. Endocrinol. 164(1), 95–100 (2011)CrossRefGoogle Scholar
  12. 12.
    N. Toyoda, E. Nomura, M. Ito, A. Harada, K. Nishimura, C. Ukita, T. Iwasaka, S. Kubota, A. Miyauchi, M. Nishikawa, Type 2 iodothyronine deiodinase activity is highly expressed in the large goiter with Hashimoto’s thyroiditis. Program of the 14th International Congress of Endocrinology. The Japan Endocrine Society (Kyoto, Japan, 2010), p S478, (Abstract P4-16-2)Google Scholar
  13. 13.
    Y. Murakami, J. Takamatsu, S. Sakane, K. Kuma, N. Ohsawa, Changes in thyroid volume in response to radioactive iodine for Graves’ hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome. J. Clin. Endocrinol. Metab. 81(9), 3257–3260 (1996)Google Scholar
  14. 14.
    D. Bellabarba, R.E. Peterson, K. Sterling, An improved method for chromatography of iodothyronines. J. Clin. Endocrinol. Metab. 28(2), 305–307 (1968)CrossRefGoogle Scholar
  15. 15.
    M. Ito, A. Miyauchi, S. Morita, T. Kudo, E. Nishihara, M. Kihara, Y. Takamura, Y. Ito, K. Kobayashi, A. Miya, S. Kubota, N. Amino, TSH-suppresive dose of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy. Eur. J. Endocrinol. 167(3), 373–378 (2012)CrossRefGoogle Scholar
  16. 16.
    B. Gereben, C. Goncalves, J.W. Harney, P.R. Larsen, A.C. Bianco, Selective proteolysis of human type 2 deiodinase: a novel ubiquitin-proteasomal mediated mechanism for regulation of hormone activation. Mol. Endocrinol. 14(11), 1697–1708 (2000)CrossRefGoogle Scholar
  17. 17.
    Y. Imai, N. Toyoda, A. Maeda, T. Kadobayashi, F. Wang, K. Kuma, M. Nishikawa, T. Iwasaka, Type 2 iodothyronine deiodinase expression is upregulated by the protein kinase A-dependent pathway and is downregulated by the protein kinase C-dependent pathway in cultured human thyroid cells. Thyroid 11(10), 899–907 (2001)CrossRefGoogle Scholar
  18. 18.
    D.L. Germain, Dual mechanisms of regulation of type I iodothyronine 5’-deiodinase in the rat kidney, liver, and thyroid gland. Implic. Treat. hyperthyroidism Radiogr. Contrast Agents J. Clin. Invest. 81(5), 1476–1484 (1988)Google Scholar
  19. 19.
    A.P. Weetman, in Werner & Ingbar’s The Thyroid, ed. by L.E. Braverman, D.S. Cooper, D.S. (eds.) 10th edn. (Lippincott Williams & Willkins, Philadelphia, 2013), pp. 525–535Google Scholar
  20. 20.
    A.L. Maia, B.W. Kim, S.A. Huang, J.W. Harney, P.R. Larsen, Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J. Clin. Invest. 115(9), 2524–2533 (2005)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Azusa Harada
    • 1
  • Emiko Nomura
    • 1
  • Kumiko Nishimura
    • 1
  • Mitsuru Ito
    • 2
  • Hiroshi Yoshida
    • 2
  • Akira Miyauchi
    • 2
  • Mitsushige Nishikawa
    • 2
  • Ichiro Shiojima
    • 1
  • Nagaoki Toyoda
    • 1
    Email author
  1. 1.Internal Medicine IIKansai Medical UniversityHirakata, OsakaJapan
  2. 2.Kuma HospitalKobeJapan

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