Non-immune-related hypothyroidism and its relationship with excess iodine



In iodine-sufficient areas, autoimmune hypothyroidism has been regarded as the major subtype of hypothyroidism. Non-immune-related hypothyroidism has received little attention because it is considered to be rare. The aim of this study was to evaluate the prevalence of non-immune-related hypothyroidism in Korea and to identify its associating factors.


A total of 6434 participants in the Korea National Health and Nutrition Examination Survey VI (2013–2015) without known thyroid disease who were examined for thyroid stimulating hormone, free thyroxine, TPO Ab, and urine iodine concentration (UIC) were enrolled. The weighted proportions, demographic variables, and severity of immune-related and non-immune-related hypothyroidism were compared. To assess the effect of iodine on hypothyroidism in TPO Ab positive or negative populations, the weighted prevalence of hypothyroidism was assessed in each population according to UIC or estimated iodine intake subgroups.


The prevalence of undetected hypothyroidism in Korea was 3.8% (n = 233). Of these 233 cases, 171 (71.8%) were non-immune-related. In the TPO Ab negative population, the prevalence of hypothyroidism was increased significantly in the subgroup with UIC between 250 and 749 µg/L (HR 2.12 [1.17, 3.83]) and ≥ 750 µg/L (HR 3.42 [1.93, 6.04]) or the subgroups with estimated iodine intake ≥ 750 µg/day (HR 2.81 [1.64, 4.80]).


This nationwide study demonstrated that most cases of hypothyroidism in iodine-sufficient areas are non-immune-related and are associated with excess iodine above a certain level. More attention to this unrecognized but widespread potential health risk is needed.

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  1. 1.

    Chaker L, Bianco AC, Jonklaas J, Peeters RP (2017) Hypothyroidism. Lancet 390:1550–1562

    CAS  Article  Google Scholar 

  2. 2.

    Szabolcs I, Podoba J, Feldkamp J, Dohan O, Farkas I, Sajgo M, Takats KI, Goth M, Kovacs L, Kressinszky K, Hnilica P, Szilagyi G (1997) Comparative screening for thyroid disorders in old age in areas of iodine deficiency, long-term iodine prophylaxis and abundant iodine intake. Clin Endocrinol (Oxf) 47:87–92

    CAS  Article  Google Scholar 

  3. 3.

    Theodoropoulou A, Vagenakis AG, Makri M, Markou KB (2007) Thyroid hormone synthesis and secretion in humans after 80 milligrams of iodine for 15 days and subsequent withdrawal. J Clin Endocrinol Metab 92:212–214

    CAS  Article  Google Scholar 

  4. 4.

    Vagenakis AG, Braverman LE (1975) Adverse effects of iodides on thyroid function. Med Clin N Am 59:1075–1088

    CAS  Article  Google Scholar 

  5. 5.

    Braverman LE, Ingbar SH (1963) Changes in thyroidal function during adaptation to large doses of iodide. J Clin Invest 42:1216–1231

    CAS  Article  Google Scholar 

  6. 6.

    Wolff J, Chaikoff IL (1948) Plasma inorganic iodide as a homeostatic regulator of thyroid function. J Biol Chem 174:555–564

    CAS  Google Scholar 

  7. 7.

    Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E, Knudsen PR (1998) Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark. J Clin Endocrinol Metab 83:765–769

    CAS  Article  Google Scholar 

  8. 8.

    Bulow Pedersen I, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P (2002) Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey. J Clin Endocrinol Metab 87:4462–4469

    Article  Google Scholar 

  9. 9.

    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 5-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 93:1751–1757

    CAS  Article  Google Scholar 

  10. 10.

    Tran BT, Jeong BY, Oh JK (2017) The prevalence trend of metabolic syndrome and its components and risk factors in Korean adults: results from the Korean National Health and Nutrition Examination Survey 2008–2013. BMC Public Health 17:71

    Article  Google Scholar 

  11. 11.

    Kwon H, Kim WG, Jeon MJ, Han M, Kim M, Park S, Kim TY, Shong YK, Kim WB (2017) Age-specific reference interval of serum TSH levels is high in adolescence in an iodine excess area: Korea national health and nutrition examination survey data. Endocrine 57:445–454

    CAS  Article  Google Scholar 

  12. 12.

    Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, Wemeau JL (2013) 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J 2:215–228

    CAS  Article  Google Scholar 

  13. 13.

    Amino N, Hagen SR, Yamada N, Refetoff S (1976) Measurement of circulating thyroid microsomal antibodies by the tanned red cell haemagglutination technique: its usefulness in the diagnosis of autoimmune thyroid diseases. Clin Endocrinol (Oxf) 5:115–125

    CAS  Article  Google Scholar 

  14. 14.

    World Health Organization, United Nations Children’s Fund, International Council for the Control of Iodine Deficiency Disorders (2017) Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers, 3rd edn. World Health Organization, Geneva. Accessed 2 Sept 2017

  15. 15.

    Zimmermann MB, Andersson M (2012) Assessment of iodine nutrition in population: past, present, and future. Nutr Rev 70:553–570

    Article  Google Scholar 

  16. 16.

    Kim HI, Oh HK, Park SY, Jang HW, Shin MH, Kim SW, Kim TH, Chung JH (2017) Urinary iodine concentration and thyroid hormones: Korea National Health and Nutrition Examination Survey 2013–2015. Eur J Nutr.

    Article  PubMed  Google Scholar 

  17. 17.

    UK Guidelines for the Use of Thyroid Function Tests (2006) Accessed 21 June 2018

  18. 18.

    Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, Sawka AM (2014) Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 24:1670–1751

    Article  Google Scholar 

  19. 19.

    Braverman LE, Cooper DS (2013) Introduction to hypothyroidism. In: Werner and Ingbar’s the thyroid, a fundamental and clinical text. Lippincott Williams & Wilkins, New York, pp 523–524

    Google Scholar 

  20. 20.

    Kim JY, Kim KR (2000) Dietary iodine intake and urinary iodine excretion in patients with thyroid diseases. Yonsei Med J 41:22–28

    CAS  Article  Google Scholar 

  21. 21.

    Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F et al (1995) The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 43:55–68

    CAS  Article  Google Scholar 

  22. 22.

    Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K (1994) Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab 78:393–397

    CAS  Google Scholar 

  23. 23.

    Vitale M, Di Matola T, D’Ascoli F, Salzano S, Bogazzi F, Fenzi G, Martino E, Rossi G (2000) Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress. Endocrinology 141:598–605

    CAS  Article  Google Scholar 

  24. 24.

    Teng X, Shan Z, Teng W, Fan C, Wang H, Guo R (2009) Experimental study on the effects of chronic iodine excess on thyroid function, structure, and autoimmunity in autoimmune-prone NOD.H-2h4 mice. Clin Exp Med 9:51–59

    CAS  Article  Google Scholar 

  25. 25.

    Joung JY, Cho YY, Park SM, Kim TH, Kim NK, Sohn SY, Kim SW, Chung JH (2014) Effect of iodine restriction on thyroid function in subclinical hypothyroid patients in an iodine-replete area: a long period observation in a large-scale cohort. Thyroid 24:1361–1368

    CAS  Article  Google Scholar 

  26. 26.

    Kasagi K, Iwata M, Misaki T, Konishi J (2003) Effect of iodine restriction on thyroid function in patients with primary hypothyroidism. Thyroid 13:561–567

    CAS  Article  Google Scholar 

  27. 27.

    Takamatsu J, Yoshida S, Yokozawa T, Hirai K, Kuma K, Ohsawa N, Hosoya T (1998) Correlation of antithyroglobulin and antithyroid-peroxidase antibody profiles with clinical and ultrasound characteristics of chronic thyroiditis. Thyroid 8:1101–1106

    CAS  Article  Google Scholar 

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The authors thank the Korea National Health and Nutrition Examination Survey for providing public access to its data.

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Correspondence to Tae Hyuk Kim or Jae Hoon Chung.

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Kim, H.I., Oh, HK., Park, S.Y. et al. Non-immune-related hypothyroidism and its relationship with excess iodine. Eur J Nutr 58, 2851–2858 (2019).

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  • Iodine-sufficient area
  • Non-immune-related hypothyroidism
  • Excess iodine