High Urinary Iodine, Thyroid Autoantibodies, and Thyroid-Stimulating Hormone for Papillary Thyroid Cancer Risk


Thyroid nodules have become a common clinical problem, and the clinical importance of thyroid nodules lies in the determination of thyroid cancer. This study aims to evaluate the risk factors for papillary thyroid cancer (PTC) with regard to urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) in comparison to thyroid nodular goiter (NG). Among the 2041 patients, 43.8% of which showed more than adequate (UIC 200–299 μg/L) and excessive iodine (UIC ≥ 300.0 μg/L) status. Compared with adequate iodine intake, iodine deficiency (UIC < 100 μg/L) was inversely associated with multifocality (OR 0.59, P = 0.040), while more than adequate iodine intake was independently associated with an increased risk of larger tumor size (OR 1.33, P = 0.002) in female PTC patients but not in males. No significant difference in UIC was observed between patients with PTC and NG, suggesting that high iodine intake may be related with the growth of PTC, but not with its oncogenesis. Besides, positive for TPOAb and TGAb were individually associated with papillary thyroid microcarcinoma (PTMC) risk (OR 2.05 and 1.71, respectively, both P < 0.05) in female patients with tumor foci < 1 cm but not in males. Furthermore, younger age (< 46 years), TGAb positivity and small thyroid nodules in both sexes, higher TSH, TPOAb positivity, and multifocality in females could all predict PTC risk (all P < 0.05). These results might have clinical significance for managing patients with thyroid nodules and those with thyroidectomy.

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  1. 1.

    Feng S, Zhang Z, Xu S, Mao X, Feng Y, Zhu Y, Liu C (2017) The prevalence of thyroid nodules and their association with metabolic syndrome risk factors in a moderate iodine intake area. Metab Syndr Relat Disord 15(2):93–97. https://doi.org/10.1089/met.2016.0077

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Gu F, Ding G, Lou X, Wang X, Mo Z, Zhu W, Zhou J, Mao G (2016) Incidence of thyroid diseases in Zhejiang Province, China, after 15 years of salt iodization. J Trace Elem Med Biol 36:57–64. https://doi.org/10.1016/j.jtemb.2016.04.003

    Article  PubMed  Google Scholar 

  3. 3.

    Song J, Zou SR, Guo CY, Zang JJ, Zhu ZN, Mi M, Huang CH, HT Y, Lu X, Ruan Y, Wu F (2016) Prevalence of thyroid nodules and its relationship with iodine status in Shanghai: a population-based study. Biomed Environ Sci 29(6):398–407. https://doi.org/10.3967/bes2016.052

    Article  PubMed  Google Scholar 

  4. 4.

    Jiang H, Tian Y, Yan W, Kong Y, Wang H, Wang A, Dou J, Liang P, Mu Y (2016) The prevalence of thyroid nodules and an analysis of related lifestyle factors in Beijing communities. Int J Environ Res Public Health 13(4):442. https://doi.org/10.3390/ijerph13040442

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, XQ Y, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66(2):115–132. https://doi.org/10.3322/caac.21338

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Davies L, Welch HG (2014) Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 140(4):317–322. https://doi.org/10.1001/jamaoto.2014.1

    Article  PubMed  Google Scholar 

  7. 7.

    Aschebrook-Kilfoy B, Kaplan EL, Chiu BC, Angelos P, Grogan RH (2013) The acceleration in papillary thyroid cancer incidence rates is similar among racial and ethnic groups in the United States. Ann Surg Oncol 20(8):2746–2753. https://doi.org/10.1245/s10434-013-2892-y

    Article  PubMed  Google Scholar 

  8. 8.

    Leboulleux S, Tuttle RM, Pacini F, Schlumberger M (2016) Papillary thyroid microcarcinoma: time to shift from surgery to active surveillance? Lancet Diabetes Endocrinol 4(11):933–942. https://doi.org/10.1016/S2213-8587(16)30180-2

    Article  PubMed  Google Scholar 

  9. 9.

    Dean DS, Gharib H (2000) Fine-Needle Aspiration Biopsy of the Thyroid Gland. In: De Groot LJ, Chrousos G, Dungan K et al. (eds) Endotext. MDText.com, Inc., South Dartmouth

  10. 10.

    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L (2016) 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26(1):1–133. https://doi.org/10.1089/thy.2015.0020

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Janczak D, Pawlowski W, Dorobisz T, Janczak D, Dorobisz K, Lesniak M, Ziomek A, Chabowski M (2016) An evaluation of the diagnostic efficacy of fine needle aspiration biopsy in patients operated for a thyroid nodular goiter. Onco Targets Ther 9:5819–5823. https://doi.org/10.2147/OTT.S111275

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Laurberg P, Cerqueira C, Ovesen L, Rasmussen LB, Perrild H, Andersen S, Pedersen IB, Carle A (2010) Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab 24(1):13–27. https://doi.org/10.1016/j.beem.2009.08.013

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Wang F, Wang Y, Wang L, Wang X, Sun C, Xing M, Zhao W (2014) Strong association of high urinary iodine with thyroid nodule and papillary thyroid cancer. Tumour Biol 35(11):11375–11379. https://doi.org/10.1007/s13277-014-2397-8

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Cao LZ, Peng XD, Xie JP, Yang FH, Wen HL, Li S (2017) The relationship between iodine intake and the risk of thyroid cancer: a meta-analysis. Medicine (Baltimore) 96(20):e6734. https://doi.org/10.1097/MD.0000000000006734

    CAS  Article  Google Scholar 

  15. 15.

    Kim HJ, Kim NK, Park HK, Byun DW, Suh K, Yoo MH, Min YK, Kim SW, Chung JH (2017) Strong association of relatively low and extremely excessive iodine intakes with thyroid cancer in an iodine-replete area. Eur J Nutr 56(3):965–971. https://doi.org/10.1007/s00394-015-1144-2

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Kim ES, Lim DJ, Baek KH, Lee JM, Kim MK, Kwon HS, Song KH, Kang MI, Cha BY, Lee KW, Son HY (2010) Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 20(8):885–891. https://doi.org/10.1089/thy.2009.0384

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Vasileiadis I, Boutzios G, Charitoudis G, Koukoulioti E, Karatzas T (2014) Thyroglobulin antibodies could be a potential predictive marker for papillary thyroid carcinoma. Ann Surg Oncol 21(8):2725–2732. https://doi.org/10.1245/s10434-014-3593-x

    Article  PubMed  Google Scholar 

  18. 18.

    Huang H, Rusiecki J, Zhao N, Chen Y, Ma S, Yu H, Ward MH, Udelsman R, Zhang Y (2017) Thyroid-stimulating hormone, thyroid hormones and risk of papillary thyroid cancer: a nested case-control study. Cancer Epidemiol Biomark Prev 26(8):1209–1218. https://doi.org/10.1158/1055-9965.EPI-16-0845

    CAS  Article  Google Scholar 

  19. 19.

    Zhao H, Tian Y, Liu Z, Li X, Feng M, Huang T (2014) Correlation between iodine intake and thyroid disorders: a cross-sectional study from the South of China. Biol Trace Elem Res 162(1-3):87–94. https://doi.org/10.1007/s12011-014-0102-9

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    WHO/UNICEF/ICCIDD (2007) Assessment of iodine deficiency disorders and monitoring their eelimination: a guide for program managers, 3rd edn. World Health Organization, Geneva

    Google Scholar 

  21. 21.

    Knobel M, Medeiros-Neto G (2007) Relevance of iodine intake as a reputed predisposing factor for thyroid cancer. Arq Bras Endocrinol Metabol 51(5):701–712. https://doi.org/10.1590/S0004-27302007000500007

    Article  PubMed  Google Scholar 

  22. 22.

    Zhao W, Han C, Shi X, Xiong C, Sun J, Shan Z, Teng W (2014) Prevalence of goiter and thyroid nodules before and after implementation of the universal salt iodization program in mainland China from 1985 to 2014: a systematic review and meta-analysis. PLoS One 9(10):e109549. https://doi.org/10.1371/journal.pone.0109549

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Latrofa F, Fiore E, Rago T, Antonangeli L, Montanelli L, Ricci D, Provenzale MA, Scutari M, Frigeri M, Tonacchera M, Vitti P (2013) Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin. J Clin Endocrinol Metab 98(11):E1768–E1774. https://doi.org/10.1210/jc.2013-2912

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Pedersen IB, Knudsen N, Carle A, Vejbjerg P, Jorgensen T, Perrild H, Ovesen L, Rasmussen LB, Laurberg P (2011) A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population. Clin Endocrinol 75(1):120–126. https://doi.org/10.1111/j.1365-2265.2011.04008.x

    CAS  Article  Google Scholar 

  25. 25.

    Shi X, Han C, Li C, Mao J, Wang W, Xie X, Li C, Xu B, Meng T, Du J, Zhang S, Gao Z, Zhang X, Fan C, Shan Z, Teng W (2015) Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China. J Clin Endocrinol Metab 100(4):1630–1638. https://doi.org/10.1210/jc.2014-3704

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Li Y, Teng D, Shan Z, Teng X, Guan H, Yu X, Fan C, Chong W, Yang F, Dai H, Gu X, Yu Y, Mao J, Zhao D, Li J, Chen Y, Yang R, Li C, Teng W (2008) Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 93(5):1751–1757. https://doi.org/10.1210/jc.2007-2368

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Li N, Jiang Y, Shan Z, Teng W (2012) Prolonged high iodine intake is associated with inhibition of type 2 deiodinase activity in pituitary and elevation of serum thyrotropin levels. Br J Nutr 107(05):674–682. https://doi.org/10.1017/S0007114511003552

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Wu X, Lun Y, Jiang H, Gang Q, Xin S, Duan Z, Zhang J (2014) Coexistence of thyroglobulin antibodies and thyroid peroxidase antibodies correlates with elevated thyroid-stimulating hormone level and advanced tumor stage of papillary thyroid cancer. Endocrine 46(3):554–560. https://doi.org/10.1007/s12020-013-0121-x

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Shi L, Li Y, Guan H, Li C, Shi L, Shan Z, Teng W (2012) Usefulness of serum thyrotropin for risk prediction of differentiated thyroid cancers does not apply to microcarcinomas: results of 1,870 Chinese patients with thyroid nodules. Endocr J 59(11):973–980. https://doi.org/10.1507/endocrj.EJ12-0154

    Article  PubMed  Google Scholar 

  30. 30.

    Hu N, Li ZM, Liu JF, Zhang ZZ, Wang LS (2016) An overall and dose-response meta-analysis for thyrotropin and thyroid cancer risk by histological type. Oncotarget 7(30):47750–47759. 10.18632/oncotarget.10282

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Gerschpacher M, Gobl C, Anderwald C, Gessl A, Krebs M (2010) Thyrotropin serum concentrations in patients with papillary thyroid microcancers. Thyroid 20(4):389–392. https://doi.org/10.1089/thy.2009.0139

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Sohn SY, Kim HJ, Jang HW, Kim SW, Chung JH (2014) Lack of association between high serum thyroid-stimulating hormone level and risk of papillary thyroid microcarcinomas. Head Neck 36(1):43–46. https://doi.org/10.1002/hed.23252

    Article  PubMed  Google Scholar 

  33. 33.

    Derwahl M, Broecker M, Kraiem Z (1999) Clinical review 101: thyrotropin may not be the dominant growth factor in benign and malignant thyroid tumors. J Clin Endocrinol Metab 84(3):829–834. https://doi.org/10.1210/jcem.84.3.5519

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Adam MA, Thomas S, Hyslop T, Scheri RP, Roman SA, Sosa JA (2016) Exploring the relationship between patient age and cancer-specific survival in papillary thyroid cancer: rethinking current staging systems. J Clin Oncol 34(36):4415–4420. https://doi.org/10.1200/JCO.2016.68.9372

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Jo K, Kim MH, Ha J, Lim Y, Lee S, Bae JS, Jung CK, Kang MI, Cha BY, Lim DJ (2017) Prognostic value of preoperative anti-thyroglobulin antibody in differentiated thyroid cancer. Clin Endocrinol 87(3):292–299. https://doi.org/10.1111/cen.13367

    CAS  Article  Google Scholar 

  36. 36.

    Cho YA, Kong SY, Shin A, Lee J, Lee EK, Lee YJ, Kim J (2014) Biomarkers of thyroid function and autoimmunity for predicting high-risk groups of thyroid cancer: a nested case-control study. BMC Cancer 14(1):873. https://doi.org/10.1186/1471-2407-14-873

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Lun Y, Wu X, Xia Q, Han Y, Zhang X, Liu Z, Wang F, Duan Z, Xin S, Zhang J (2013) Hashimoto’s thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis. Otolaryngol Head Neck Surg 148(3):396–402. https://doi.org/10.1177/0194599812472426

    Article  PubMed  Google Scholar 

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The authors gratefully acknowledge all the staff from Union Hospital in Wuhan for their kindly cooperation. We thank Prof. Yingjie Wang in the School of Foreign Languages, Huazhong University of Science and Technology, Wuhan 430000, China, for proofreading and editing this manuscript.

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Correspondence to Hengqiang Zhao or Tao Huang.

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Zhao, H., Li, H. & Huang, T. High Urinary Iodine, Thyroid Autoantibodies, and Thyroid-Stimulating Hormone for Papillary Thyroid Cancer Risk. Biol Trace Elem Res 184, 317–324 (2018). https://doi.org/10.1007/s12011-017-1209-6

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  • Iodine
  • Thyroid thyroglobulin antibody
  • Thyroid-stimulating hormone
  • Papillary thyroid cancer
  • Microcarcinoma
  • Risk factors