Endocrine

, Volume 56, Issue 2, pp 399–407 | Cite as

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

  • Roghaieh Samadi
  • Mahboubeh Ghanbari
  • Babak Shafiei
  • Sevda Gheibi
  • Fereidoun Azizi
  • Asghar Ghasemi
Original Article

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.

Keywords

Radioactive iodine Sodium-iodide symporter Glucose metabolism Thyroidectomy Rat 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

References

  1. 1.
    C.T. Sawin, D.V. Becker, Radioiodine and the treatment of hyperthyroidism: the early history. Thyroid 7, 163–176 (1997)CrossRefPubMedGoogle Scholar
  2. 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)CrossRefPubMedGoogle Scholar
  3. 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)CrossRefPubMedGoogle Scholar
  4. 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)CrossRefPubMedGoogle Scholar
  5. 5.
    O. Levy, A. De la Vieja, N. Carrasco, The Na+/I− symporter (NIS): recent advances. J. Bioenerg. Biomembr 30, 195–206 (1998)CrossRefPubMedGoogle Scholar
  6. 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)Google Scholar
  7. 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. 943–992Google Scholar
  8. 8.
    R. Samadi, B. Shafiei, F. Azizi, A. Ghasemi, Radioactive iodine therapy and glucose tolerance. Cell J. 19, 184–193 (2017)Google Scholar
  9. 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)CrossRefPubMedGoogle Scholar
  10. 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)PubMedGoogle Scholar
  11. 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)CrossRefPubMedGoogle Scholar
  12. 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)CrossRefPubMedGoogle Scholar
  13. 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)CrossRefPubMedGoogle Scholar
  14. 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)PubMedGoogle Scholar
  15. 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)CrossRefPubMedGoogle Scholar
  16. 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)PubMedGoogle Scholar
  17. 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. 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. 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)Google Scholar
  20. 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)CrossRefPubMedGoogle Scholar
  21. 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)PubMedGoogle Scholar
  22. 22.
    D. Piciu. Nuclear Endocrinology. (Springer Science & Business Media, Heidelberg, (2012)CrossRefGoogle Scholar
  23. 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)CrossRefPubMedGoogle Scholar
  24. 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. 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)CrossRefPubMedGoogle Scholar
  26. 26.
    P.E. Lacy, M. Kostianovsky, Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16, 35–39 (1967)CrossRefPubMedGoogle Scholar
  27. 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)CrossRefPubMedGoogle Scholar
  28. 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)CrossRefPubMedGoogle Scholar
  29. 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)CrossRefPubMedGoogle Scholar
  30. 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)CrossRefPubMedGoogle Scholar
  31. 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)CrossRefPubMedGoogle Scholar
  32. 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)CrossRefPubMedGoogle Scholar
  33. 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)CrossRefPubMedGoogle Scholar
  34. 34.
    W.J. Malaisse, F. Malaisse-Lagae, E.F. McCraw, Effects of thyroid function upon insulin secretion. Diabetes 16, 643–646 (1967)CrossRefPubMedGoogle Scholar
  35. 35.
    M. Gierach, J. Gierach, R. Junik, Insulin resistance and thyroid disorders. Endokrynol. Pol. 65, 70–76 (2014)CrossRefPubMedGoogle Scholar
  36. 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)CrossRefGoogle Scholar
  37. 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)CrossRefGoogle Scholar
  38. 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)CrossRefPubMedGoogle Scholar
  39. 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)CrossRefPubMedGoogle Scholar
  40. 40.
    A.M. Nada, Effect of treatment of overt hypothyroidism on insulin resistance. World J. Diabetes 4, 157–161 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  41. 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)CrossRefPubMedPubMedCentralGoogle Scholar
  42. 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)CrossRefPubMedGoogle Scholar
  43. 43.
    M.A. Pisarev, Interrelationships between the pancreas and the thyroid. Curr. Opin. Endocrinol. Diabetes Obes. 17, 437–439 (2010)CrossRefPubMedGoogle Scholar
  44. 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)CrossRefPubMedGoogle Scholar
  45. 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)PubMedGoogle Scholar
  46. 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)PubMedGoogle Scholar
  47. 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)CrossRefPubMedGoogle Scholar
  48. 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)CrossRefPubMedGoogle Scholar
  49. 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)CrossRefPubMedGoogle Scholar
  50. 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)PubMedGoogle Scholar
  51. 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)CrossRefPubMedGoogle Scholar
  52. 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)CrossRefPubMedPubMedCentralGoogle Scholar
  53. 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)CrossRefPubMedPubMedCentralGoogle Scholar
  54. 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)CrossRefPubMedGoogle Scholar
  55. 55.
    A. Muniesa, M. Llobera, E. Herrera, Adipose tissue cellularity in hypo- and hyperthyroid rats. Horm. Res. Paediatr. 11, 254–261 (1979)CrossRefGoogle Scholar
  56. 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. 327–475CrossRefGoogle Scholar
  57. 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)CrossRefPubMedGoogle Scholar
  58. 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)CrossRefPubMedGoogle Scholar
  59. 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. 262Google Scholar
  60. 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)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Roghaieh Samadi
    • 1
  • Mahboubeh Ghanbari
    • 1
  • Babak Shafiei
    • 2
  • Sevda Gheibi
    • 1
  • Fereidoun Azizi
    • 3
  • Asghar Ghasemi
    • 1
  1. 1.Endocrine Physiology Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Nuclear Medicine, Taleghani HospitalShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Endocrine Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran

Personalised recommendations