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High dose of radioactive iodine per se has no effect on glucose metabolism in thyroidectomized rats

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Abstract

Purpose

Thyroid concentrates radioactive iodine by sodium-iodide symporter; this is used for treating hyperthyroidism and thyroid cancer. Pancreas expresses NIS and radioactive iodine uptake may damage pancreatic beta-cells and predispose patients to type 2 diabetes. The aim of this study was to determine whether radioactive iodine is associated with glucose metabolism in thyroidectomized rats.

Methods

Forty male Wistar rats were divided into four groups (n = 10/each); control, thyroidectomized, thyroidectomized-treated with 131-I (TX+I), and thyroidectomized-treated with 131-I and l-thyroxine (TX+I+T4). At the end of study, serum fasting glucose, insulin, thyroid-stimulating hormone, and free tetraiodothyronine were measured, intraperitoneal glucose tolerance test was performed, and homeostasis model assessment-insulin resistance was calculated. In in vitro experiments, glucose-stimulated insulin secretion from pancreatic islets and sodium-iodide symporter mRNA expression in thyroid and islets were determined.

Results

Compared to control group, free tetraiodothyronine was lower by 41 and 77% and thyroid-stimulating hormone was higher by 36 and 126% in thyroidectomized and TX+I groups, respectively. Compared to controls, rats in TX+I group had glucose intolerance as assessed using the area under curve of intraperitoneal glucose tolerance test (12,376 ± 542 vs. 20,769 ± 1070, P < 0.001) and l-thyroxine replacement therapy restored the value (14,286 ± 328.24) to near normal. Fasting insulin and homeostasis model assessment-insulin resistance were comparable in all groups, however fasting glucose was higher in TX+I group. In in vitro experiments, glucose-stimulated insulin secretion from islets did not differ between groups.

Conclusion

Radioactive iodine therapy per se had no effect on glucose metabolism, just intensified thyroid hormone deficiency and the alterations on glucose metabolism in thyroidectomized rats. l-thyroxine therapy restored the glucose intolerance observed in radioactive iodine-treated thyroidectomized rats.

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References

  1. C.T. Sawin, D.V. Becker, Radioiodine and the treatment of hyperthyroidism: the early history. Thyroid 7, 163–176 (1997)

    Article  CAS  Google Scholar 

  2. D.A. Pryma, S.J. Mandel, Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies. J. Nucl. Med. 55, 1485–1491 (2014)

    Article  CAS  Google Scholar 

  3. J.K. Fernandes, T.A. Day, M.S. Richardson, A.K. Sharma, Overview of the management of differentiated thyroid cancer. Curr. Treat. Options Oncol. 6, 47–57 (2005)

    Article  Google Scholar 

  4. O. Dohan, A. De la Vieja, V. Paroder, C. Riedel, M. Artani, M. Reed et al., The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr. Rev. 24, 48–77 (2003)

    Article  CAS  Google Scholar 

  5. O. Levy, A. De la Vieja, N. Carrasco, The Na+/I− symporter (NIS): recent advances. J. Bioenerg. Biomembr 30, 195–206 (1998)

    Article  CAS  Google Scholar 

  6. P.S. Sundaram, S. Padma, S. Sudha, K. Sasikala, Transient cytotoxicity of 131I beta radiation in hyperthyroid patients treated with radioactive iodine. Indian J. Med. Res. 133, 401–406 (2011)

  7. S.A. Rivkees, C. Dinauer. The use of 131 Iodine in the treatment of Graves’ disease in children. in Comprehensive Handbook of Iodine: Nutritional, Biochemical, Pathological and Therapeutic Aspects. ed. by V.R. Preedy, G.N. Burrow, R. Watson (Academic, Boston, MA, 2009), pp. 943–992

    Google Scholar 

  8. R. Samadi, B. Shafiei, F. Azizi, A. Ghasemi, Radioactive iodine therapy and glucose tolerance. Cell J. 19, 184–193 (2017)

    PubMed  PubMed Central  Google Scholar 

  9. W. Grzesiuk, J. Nieminuszczy, M. Kruszewski, T. Iwanienko, M. Plazinska, M. Bogdanska et al., DNA damage and its repair in lymphocytes and thyroid nodule cells during radioiodine therapy in patients with hyperthyroidism. J. Mol. Endocrinol. 37, 527–532 (2006)

    Article  CAS  Google Scholar 

  10. C. Spitzweg, W. Joba, K. Schriever, J.R. Goellner, J.C. Morris, A.E. Heufelder, Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands. J. Clin. Endocrinol. Metab. 84, 4178–4184 (1999)

    CAS  PubMed  Google Scholar 

  11. L. Vayre, J.-C. Sabourin, B. Caillou, M. Ducreux, M. Schlumberger, J.-M. Bidart, Immunohistochemical analysis of Na+/I-symporter distribution in human extra-thyroidal tissues. Eur. J. Endocrinol. 141, 382–386 (1999)

    Article  CAS  Google Scholar 

  12. C. Spitzweg, W. Joba, W. Eisenmenger, A.E. Heufelder, Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J. Clin. Endocrinol. Metab. 83, 1746–1751 (1998)

    Article  CAS  Google Scholar 

  13. I.L. Wapnir, M. van de Rijn, K. Nowels, P.S. Amenta, K. Walton, K. Montgomery et al., Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. J. Clin. Endocrinol. Metab. 88, 1880–1888 (2003)

    Article  CAS  Google Scholar 

  14. T. Mitsuma, N. Rhue, Y. Hirooka, M. Kayama, Y. Yokoi, Y. Mori et al., Organ distribution of iodide transporter (symporter) in the rat: immunohistochemical study. Endocr. Regul. 31, 15–18 (1997)

    CAS  PubMed  Google Scholar 

  15. R.M. Dwyer, E.R. Bergert, M.K. O’Connor, S.J. Gendler, J.C. Morris, Adenovirus-mediated and targeted expression of the sodium-iodide symporter permits in vivo radioiodide imaging and therapy of pancreatic tumors. Hum. Gene Ther. 17, 661–668 (2006)

    Article  CAS  Google Scholar 

  16. R. Solans, J.-A. Bosch, P. Galofre, F. Porta, J. Rosello, A. Selva-O Callagan et al., Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy. J. Nucl. Med. 42, 738–743 (2001)

    CAS  PubMed  Google Scholar 

  17. N. Eijun, K. Masafumi, Glucose tolerance evaluation in graves patients treated with methimazole and radioiodine. Int. J. Endocrinol. Metab 2011, 377–378 (2011)

    Google Scholar 

  18. S.A. Durmaz, A. Carlioglu, E. Simsek, M. Demirci, H. Sevimli, Does radioactive iodine ablation treatment in patients with hyperthyroidism effect on glucose metabolism? Endocrine 35, 1025 (2014)

    Google Scholar 

  19. J. Kiani, V. Yusefi, M. Tohidi, Y. Mehrabi, F. Azizi, Evaluation of glucose tolerance in methimazole and radioiodine treated Graves’ patients. Int. J. Endocrinol. Metab. 8, 132–137 (2010)

    CAS  Google Scholar 

  20. B. Hallengren, A. Falorni, M. Landin-Olsson, A. Lernmark, K.I. Papadopoulos, G. Sundkvist, Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients: at diagnosis and following treatment. J. Intern. Med. 239, 63–68 (1996)

    Article  CAS  Google Scholar 

  21. R.J. Robbins, M.J. Schlumberger, The evolving role of 131I for the treatment of differentiated thyroid carcinoma. J. Nucl. Med. 46, 28S–37S (2005)

    CAS  PubMed  Google Scholar 

  22. D. Piciu. Nuclear Endocrinology. (Springer Science & Business Media, Heidelberg, (2012)

    Book  Google Scholar 

  23. M. Luster, S.E. Clarke, M. Dietlein, M. Lassmann, P. Lind, W.J.G. Oyen et al., Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur. J. Nucl. Med. Mol. Imaging 35, 1941–1959 (2008)

    Article  CAS  Google Scholar 

  24. J.C. Francisco, R.C. Cunha, M.A. Cardoso, R.B. Simeoni, L.C. Guarita-Souza, The effects of total thyroidectomy on cardiac function in old rats using echocardiographic measures. J. Clin. Exp. Cardiol. 11, 2–5 (2013)

    Google Scholar 

  25. L.A. Nolan, C.K. Thomas, A. Levy, Permissive effects of thyroid hormones on rat anterior pituitary mitotic activity. J. Endocrinol. 180, 35–43 (2004)

    Article  CAS  Google Scholar 

  26. P.E. Lacy, M. Kostianovsky, Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16, 35–39 (1967)

    Article  CAS  Google Scholar 

  27. N. Karbalaei, A. Ghasemi, F. Faraji, S. Zahediasl, Comparison of the effect of maternal hypothyroidism on carbohydrate metabolism in young and aged male offspring in rats. Scand. J. Clin. Lab. Invest. 73, 87–94 (2013)

    Article  CAS  Google Scholar 

  28. M. Tohidi, A. Ghasemi, F. Hadaegh, A. Derakhshan, A. Chary, F. Azizi, Age- and sex-specific reference values for fasting serum insulin levels and insulin resistance/sensitivity indices in healthy Iranian adults: tehran lipid and glucose study. Clin. Biochem. 47, 432–438 (2014)

    Article  CAS  Google Scholar 

  29. A. Godini, A. Ghasemi, N. Karbalaei, S. Zahediasl, The effect of thyroidectomy and propylthiouracil-induced hypothyroidism on insulin secretion in male rats. Horm. Metab. Res. 46, 710–716 (2014)

    Article  CAS  Google Scholar 

  30. M.-L. Doong, J.W.-C. Wang, S.-C. Chung, J.-Y. Liu, C. Hwang, C.-Y. Hwang et al., Regulation of thyroid hormones in the secretion of insulin and gastric inhibitory polypeptide in male rats. Metabolism 46, 154–158 (1997)

    Article  CAS  Google Scholar 

  31. H. Nagao, T. Imazu, H. Hayashi, K. Takahashi, K. Minato, Influence of thyroidectomy on thyroxine metabolism and turnover rate in rats. J. Endocrinol. 210, 117–123 (2011)

    Article  CAS  Google Scholar 

  32. N. Katsilambros, R. Ziegler, H. Schatz, M. Hinz, V. Maier, E.F. Pfeiffer, Intravenous glucose tolerance and insulin secretion in the rat after thyroidectomy. Horm. Metab. Res. 4, 377–379 (1972)

    Article  CAS  Google Scholar 

  33. S. Lenzen, H.G. Joost, A. Hasselblatt, Thyroid function and insulin secretion from the perfused pancreas in the rat. Endocrinology 99, 125–129 (1976)

    Article  CAS  Google Scholar 

  34. W.J. Malaisse, F. Malaisse-Lagae, E.F. McCraw, Effects of thyroid function upon insulin secretion. Diabetes 16, 643–646 (1967)

    Article  CAS  Google Scholar 

  35. M. Gierach, J. Gierach, R. Junik, Insulin resistance and thyroid disorders. Endokrynol. Pol. 65, 70–76 (2014)

    Article  Google Scholar 

  36. A. Handisurya, G. Pacini, A. Tura, A. Gessl, A. Kautzky-Willer, Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH). Clin. Endocrinol. 69, 963–969 (2008)

    Article  CAS  Google Scholar 

  37. A. Montes, F. Hervas, T. John, Effects of thyroidectomy and thyroxine on plasma growth hormone and insulin levels in rats. Hormones 8, 148–158 (1977)

    Article  CAS  Google Scholar 

  38. N. Dariyerli, G. Andican, A.B. Catakoglu, H. Hatemi, G. Burcak, Hyperuricemia in hypothyroidism: is it associated with post-insulin infusion glycemic response? Tohoku J. Exp. Med. 199, 59–68 (2003)

    Article  Google Scholar 

  39. M. Owecki, E. Nikisch, J. Sowinski, Hypothyroidism has no impact on insulin sensitivity assessed with HOMA-IR in totally thyroidectomized patients. Acta Clin. Belg. 61, 69–73 (2006)

    Article  CAS  Google Scholar 

  40. A.M. Nada, Effect of treatment of overt hypothyroidism on insulin resistance. World J. Diabetes 4, 157–161 (2013)

    Article  Google Scholar 

  41. G. Brenta, F.S. Celi, M. Pisarev, M. Schnitman, I. Sinay, P. Arias, Acute thyroid hormone withdrawal in athyreotic patients results in a state of insulin resistance. Thyroid 19, 665–669 (2009)

    Article  CAS  Google Scholar 

  42. G. Dimitriadis, P. Mitrou, V. Lambadiari, E. Boutati, E. Maratou, D.B. Panagiotakos et al., Insulin action in adipose tissue and muscle in hypothyroidism. J. Clin. Endocrinol. Metab. 91, 4930–4937 (2006)

    Article  CAS  Google Scholar 

  43. M.A. Pisarev, Interrelationships between the pancreas and the thyroid. Curr. Opin. Endocrinol. Diabetes Obes. 17, 437–439 (2010)

    Article  CAS  Google Scholar 

  44. G. Dimitriadis, E. Maratou, M. Alevizaki, E. Boutati, K. Psara, C. Papasteriades et al., Thyroid hormone excess increases basal and insulin-stimulated recruitment of GLUT3 glucose transporters on cell surface. Horm. Metab. Res. 37, 15–20 (2005)

    Article  CAS  Google Scholar 

  45. A.M. Cortizo, D.C.L. Gomez, J.J. Gagliardino, Effect of thyroid hormone levels upon pancreatic islet function. Acta Physiol. Pharmacol. Latinoam. 35, 181–191 (1985)

    CAS  PubMed  Google Scholar 

  46. G. Dimitriadis, B. Baker, H. Marsh, L. Mandarino, R. Rizza, R. Bergman et al., Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am. J. Physiol. 248, E593–E601 (1985)

    CAS  PubMed  Google Scholar 

  47. C.P. Reilly, R.G. Symons, M.L. Wellby, A rat model of the 131I-induced changes in thyroid function. J. Endocrinol. Invest. 9, 367–370 (1986)

    Article  CAS  Google Scholar 

  48. V. Torlak, T. Zemunik, D. Modun, V. Capkun, V. Pesutic-Pisac, A. Markotic et al., 131I-induced changes in rat thyroid gland function. Braz. J. Med. Biol. Res. 40, 1087–1094 (2007)

    Article  CAS  Google Scholar 

  49. N. Karbalaei, A. Ghasemi, M. Hedayati, A. Godini, S. Zahediasl, The possible mechanisms by which maternal hypothyroidism impairs insulin secretion in adult male offspring in rats. Exp. Physiol. 99, 701–714 (2014)

    Article  CAS  Google Scholar 

  50. C. Alva-Sánchez, J. Pacheco-Rosado, T. Fregoso-Aguilar, I. Villanueva, The long-term regulation of food intake and body weight depends on the availability of thyroid hormones in the brain. Neuroendocrinol. Lett. 33, 703–708 (2012)

    PubMed  Google Scholar 

  51. V. Usenko, E. Lepekhin, V. Lyzogubov, I. Kornilovska, G. Ushakova, M. Witt, The influence of low doses 131 I-induced maternal hypothyroidism on the development of rat embryos. Exp. Toxicol. Pathol. 51, 223–227 (1999)

    Article  CAS  Google Scholar 

  52. S. Wu, G. Tan, X. Dong, Z. Zhu, W. Li, Z. Lou et al., Metabolic profiling provides a system understanding of hypothyroidism in rats and its application. PLoS One. 8, e55599 (2013)

    Article  CAS  Google Scholar 

  53. A. Herwig, G. Campbell, C.-D. Mayer, A. Boelen, R.A. Anderson, A.W. Ross et al., A thyroid hormone challenge in hypothyroid rats identifies T3 regulated genes in the hypothalamus and in models with altered energy balance and glucose homeostasis. Thyroid 24, 1575–1593 (2014)

    Article  CAS  Google Scholar 

  54. M.A. Syed, M.P. Thompson, J. Pachucki, L.A. Burmeister, The effect of thyroid hormone on size of fat depots accounts for most of the changes in leptin mRNA and serum levels in the rat. Thyroid 9, 503–512 (1999)

    Article  CAS  Google Scholar 

  55. A. Muniesa, M. Llobera, E. Herrera, Adipose tissue cellularity in hypo- and hyperthyroid rats. Horm. Res. Paediatr. 11, 254–261 (1979)

    Article  CAS  Google Scholar 

  56. D. Salvatore, T.F. Davies, M. Schlumberger, I.D. Hay, P.R. Larsen. Thyroid physiology and diagnostic evaluation of patients with thyroid disorders. Williams Textbook of Endocrinology. ed. by S. Melmed, K.S. Polonsky, P.R. Larsen, H.M. Kronenberg (Elsevier Health Sciences, Philadelphia, PA, 2011) pp. 327–475

    Chapter  Google Scholar 

  57. C. La Vecchia, M. Malvezzi, C. Bosetti, W. Garavello, P. Bertuccio, F. Levi et al., Thyroid cancer mortality and incidence: a global overview. Int. J. Cancer 136, 2187–2195 (2015)

    Article  Google Scholar 

  58. S. Reichlin, J.B. Martin, R.L. Boshans, D.S. Schalch, J.G. Pierce, J. Bollinger, Measurement of TSH in plasma and pituitary of the rat by a radioimmunoassay utilizing bovine TSH: effect of thyroidectomy or thyroxine administration on plasma TSH levels. Endocrinology 87, 1022–1031 (1970)

    Article  CAS  Google Scholar 

  59. J.W. Fisher, E.D. McLanahan. Computational model for iodide economy and the HPT axis in the adult rat. Quantitative Modeling in Toxicology. ed. by M.E.A. Kannan Krishnan (Wiley, Chichester, 2010) p. 262

    Google Scholar 

  60. N. Tonooka, S. Kobayashi, Effect of propylthiouracil on nycthemeral and sex related variation of plasma TSH in rats. Endocrinol. Jpn 27, 27–32 (1980)

    Article  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank Ms. Niloofar. Shiva for critical editing for English grammar and syntax of the manuscript. The proposal of this study was approved by the ethics committee of the Research Institute for Endocrine Science (RIES), Shahid Beheshti University of Medical Science. This study was supported by grant number No. 768 from the RIES.

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Authors and Affiliations

  1. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Roghaieh Samadi, Mahboubeh Ghanbari, Sevda Gheibi & Asghar Ghasemi

  2. Department of Nuclear Medicine, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Babak Shafiei

  3. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fereidoun Azizi

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  1. Roghaieh Samadi
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Correspondence to Asghar Ghasemi.

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Samadi, R., Ghanbari, M., Shafiei, B. et al. High dose of radioactive iodine per se has no effect on glucose metabolism in thyroidectomized rats. Endocrine 56, 399–407 (2017). https://doi.org/10.1007/s12020-017-1274-9

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