Endocrinol Metab.  2014 Mar;29(1):20-29. 10.3803/EnM.2014.29.1.20.

Prevalence and Risk Factors of Subclinical Thyroid Disease

• Kim YA
• Park YJ

• KMID: 2169347
• DOI: http://doi.org/10.3803/EnM.2014.29.1.20

Abstract

Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin (TSH) level and normal serum-free thyroxine level. The prevalence of this condition varies according to the reference range for TSH and geographic or demographic factors. Recently, several studies, including our community-based cohort studies, have reported on the incidence of subclinical thyroid disease in Korea. Using these studies, we reviewed the prevalence and risk factors of subclinical thyroid disease, focusing on subclinical hypothyroidism.

Keyword

Prevalence; Risk factors; Subclinical hypothyroidism; Subclinical hyperthyroidism

MeSH Terms

Cohort Studies
Demography
Hypothyroidism
Incidence
Korea
Prevalence*
Reference Values
Risk Factors*
Thyroid Diseases*
Thyroid Gland*
Thyrotropin
Thyroxine
Thyrotropin
Thyroxine

Figure

• 

  Fig. 1 Prevalence of subclinical hypothyroidism according to age in the (A) Ansung cohort and (B) Korean Longitudinal Study on Health and Aging study (KLoSHA). Adapted from Choi et al. J Korean Thyroid Assoc 2010;3:32-40 [36].

Reference

1. Cooper DS. Subclinical hypothyroidism. JAMA. 1987; 258:246–247. PMID: 3599312.

2. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008; 29:76–131. PMID: 17991805.

3. Bell RJ, Rivera-Woll L, Davison SL, Topliss DJ, Donath S, Davis SR. Well-being, health-related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease: a community-based study. Clin Endocrinol (Oxf). 2007; 66:548–556. PMID: 17371474.

4. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, Bremner A, Maisonneuve P, Sgarbi JA, Khaw KT, Vanderpump MP, Newman AB, Cornuz J, Franklyn JA, Westendorp RG, Vittinghoff E, Gussekloo J. Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010; 304:1365–1374. PMID: 20858880.

5. Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, Nanchen D, den Elzen WP, Balmer P, Luben RN, Iacoviello M, Triggiani V, Cornuz J, Newman AB, Khaw KT, Jukema JW, Westendorp RG, Vittinghoff E, Aujesky D, Rodondi N. Thyroid Studies Collaboration. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012; 126:1040–1049. PMID: 22821943.

6. Aghini-Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R, Balestrieri A, Pinchera A. The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. J Clin Endocrinol Metab. 1999; 84:561–566. PMID: 10022416.

7. Iervasi G, Molinaro S, Landi P, Taddei MC, Galli E, Mariani F, L'Abbate A, Pingitore A. Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch Intern Med. 2007; 167:1526–1532. PMID: 17646607.

8. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med. 2000; 132:270–278. PMID: 10681281.

9. Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004; 292:2591–2599. PMID: 15572717.

10. Walsh JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, Michelangeli V. Subclinical thyroid dysfunction and blood pressure: a community-based study. Clin Endocrinol (Oxf). 2006; 65:486–491. PMID: 16984241.

11. Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the Framingham Study. Arch Intern Med. 1985; 145:1386–1388. PMID: 4026469.

12. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87:489–499. PMID: 11836274.

13. Bagchi N, Brown TR, Parish RF. Thyroid dysfunction in adults over age 55 years. A study in an urban US community. Arch Intern Med. 1990; 150:785–787. PMID: 2109585.

14. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000; 160:526–534. PMID: 10695693.

15. Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, Bauer DC. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med. 2005; 165:2460–2466. PMID: 16314541.

16. Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977; 7:481–493. PMID: 598014.

17. Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf). 1991; 34:77–83. PMID: 2004476.

18. Boekholdt SM, Titan SM, Wiersinga WM, Chatterjee K, Basart DC, Luben R, Wareham NJ, Khaw KT. Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk prospective population study. Clin Endocrinol (Oxf). 2010; 72:404–410. PMID: 19486022.

19. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA, Gorman C, Cooper RS, Weissman NJ. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004; 291:228–238. PMID: 14722150.

20. Sgarbi JA, Villaca FG, Garbeline B, Villar HE, Romaldini JH. The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J Clin Endocrinol Metab. 2003; 88:1672–1677. PMID: 12679455.

21. Faber J, Jensen IW, Petersen L, Nygaard B, Hegedus L, Siersbaek-Nielsen K. Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women. Clin Endocrinol (Oxf). 1998; 48:285–290. PMID: 9578817.

22. Imaizumi M, Sera N, Ueki I, Horie I, Ando T, Usa T, Ichimaru S, Nakashima E, Hida A, Soda M, Tominaga T, Ashizawa K, Maeda R, Nagataki S, Akahoshi M. Risk for progression to overt hypothyroidism in an elderly Japanese population with subclinical hypothyroidism. Thyroid. 2011; 21:1177–1182. PMID: 21877935.

23. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012; 379:1142–1154. PMID: 22273398.

24. Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN. American Thyroid Association. American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011; 17:456–520. PMID: 21700562.

25. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F, Young ET. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995; 43:55–68. PMID: 7641412.

26. Laurberg P, Pedersen KM, Hreidarsson A, Sigfusson N, Iversen E, Knudsen PR. 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. 1998; 83:765–769. PMID: 9506723.

27. Teng W, Shan Z, Teng X, Guan H, Li Y, Teng D, Jin Y, Yu X, Fan C, Chong W, Yang F, Dai H, Yu Y, Li J, Chen Y, Zhao D, Shi X, Hu F, Mao J, Gu X, Yang R, Tong Y, Wang W, Gao T, Li C. Effect of iodine intake on thyroid diseases in China. N Engl J Med. 2006; 354:2783–2793. PMID: 16807415.

28. Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab. 1994; 78:393–397. PMID: 8106628.

29. Chung JH, Kim BJ, Choi YH, Shin MH, Kim SH, Min YK, Lee MS, Lee MG, Kim KW. Prevalence of thyrotoxicosis and hypothyroidism in the subjects for health check-up. J Korean Soc Endocrinol. 1999; 14:301–313.

30. Choi JK, Kim JS, Hwang CH, Kim DH, Hwang SW, Cho B, Jul BY. Subclinical hypothyroidism and coronary risk factors in women above 55 years. J Korean Acad Fam Med. 2002; 23:96–103.

31. Oh MK, Cheon KS, Jung SM, Ryu DS, Park MS, Cheong SS, Kim JS, Park BG. Prevalence of thyroid diseases among adult for health check-up in a Youngdong area of Kwangwon province. J Korean Acad Fam Med. 2001; 22:1363–1374.

32. Jung CH, Sung KC, Shin HS, Rhee EJ, Lee WY, Kim BS, Kang JH, Kim H, Kim SW, Lee MH, Park JR, Kim SW. Thyroid dysfunction and their relation to cardiovascular risk factors such as lipid profile, hsCRP, and waist hip ratio in Korea. Korean J Intern Med. 2003; 18:146–153. PMID: 14619383.

33. Lee WY, Oh KW, Rhee EJ, Jung CH, Kim SW, Yun EJ, Tae HJ, Baek KH, Kang MI, Choi MG, Yoo HJ, Park SW. Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res. 2006; 37:511–516. PMID: 16624651.

34. Park HY, Lee SI, Kim WB, Kim SY, Cho BY, Lee HK, Koh CS. A study on the urinary iodine excretion in normal subjects and patients with thyroid disease. J Korean Soc Endocrinol. 1995; 10:386–394.

35. Cho NH, Choi HS, Kim KW, Kim HL, Lee SY, Choi SH, Lim S, Park YJ, Park do J, Jang HC, Cho BY. Interaction between cigarette smoking and iodine intake and their impact on thyroid function. Clin Endocrinol (Oxf). 2010; 73:264–270. PMID: 20105185.

36. Choi HS, Park YJ, Kim HK, Choi SH, Lim S, Park DJ, Jang HC, Cho NH, Cho BY. Prevalence of subclinical hypothyroidism in two population based-cohort: Ansung and KLoSHA cohort in Korea. J Korean Thyroid Assoc. 2010; 3:32–40.

37. Völzke H, Alte D, Kohlmann T, Ludemann J, Nauck M, John U, Meng W. Reference intervals of serum thyroid function tests in a previously iodine-deficient area. Thyroid. 2005; 15:279–285. PMID: 15785248.

38. de Benoist B, McLean E, Andersson M, Rogers L. Iodine deficiency in 2007: global progress since 2003. Food Nutr Bull. 2008; 29:195–202. PMID: 18947032.

39. Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PW, Hershman JM. Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med. 1991; 151:165–168. PMID: 1985591.

40. Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med. 2001; 344:1743–1749. PMID: 11396440.

41. Pedersen IB, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of populations with mild and moderate iodine deficiency. Clin Endocrinol (Oxf). 2003; 58:36–42. PMID: 12519410.

42. Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab. 2007; 92:4575–4582. PMID: 17911171.

43. Vadiveloo T, Donnan PT, Murphy MJ, Leese GP. Age- and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS). J Clin Endocrinol Metab. 2013; 98:1147–1153. PMID: 23345094.

44. Bremner AP, Feddema P, Leedman PJ, Brown SJ, Beilby JP, Lim EM, Wilson SG, O'Leary PC, Walsh JP. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab. 2012; 97:1554–1562. PMID: 22344200.

45. Aggarwal N, Razvi S. Thyroid and aging or the aging thyroid? An evidence-based analysis of the literature. J Thyroid Res. 2013; 2013:481287. PMID: 24106641.

46. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA. American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012; 18:988–1028. PMID: 23246686.

47. Roberts CG, Ladenson PW. Hypothyroidism. Lancet. 2004; 363:793–803. PMID: 15016491.

48. Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases. J Clin Endocrinol Metab. 1990; 71:661–669. PMID: 2168432.

49. Mahmoud I, Colin I, Many MC, Denef JF. Direct toxic effect of iodide in excess on iodine-deficient thyroid glands: epithelial necrosis and inflammation associated with lipofuscin accumulation. Exp Mol Pathol. 1986; 44:259–271. PMID: 3720915.

50. Sharma RB, Alegria JD, Talor MV, Rose NR, Caturegli P, Burek CL. Iodine and IFN-gamma synergistically enhance intercellular adhesion molecule 1 expression on NOD.H2h4 mouse thyrocytes. J Immunol. 2005; 174:7740–7745. PMID: 15944276.

51. Kim TH, Kim KW, Ahn HY, Choi HS, Won H, Choi Y, Cho SW, Moon JH, Yi KH, Park do J, Park KS, Jang HC, Kim SY, Park YJ. Effect of seasonal changes on the transition between subclinical hypothyroid and euthyroid status. J Clin Endocrinol Metab. 2013; 98:3420–3429. PMID: 23771919.

52. Belin RM, Astor BC, Powe NR, Ladenson PW. Smoke exposure is associated with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation and a higher prevalence of mild thyrotropin concentration suppression in the third National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2004; 89:6077–6086. PMID: 15579761.

53. Pedersen IB, Laurberg P, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Rasmussen LB. Smoking is negatively associated with the presence of thyroglobulin autoantibody and to a lesser degree with thyroid peroxidase autoantibody in serum: a population study. Eur J Endocrinol. 2008; 158:367–373. PMID: 18299471.

54. Fukayama H, Nasu M, Murakami S, Sugawara M. Examination of antithyroid effects of smoking products in cultured thyroid follicles: only thiocyanate is a potent antithyroid agent. Acta Endocrinol (Copenh). 1992; 127:520–525. PMID: 1283478.

55. Nizri E, Irony-Tur-Sinai M, Lory O, Orr-Urtreger A, Lavi E, Brenner T. Activation of the cholinergic anti-inflammatory system by nicotine attenuates neuroinflammation via suppression of Th1 and Th17 responses. J Immunol. 2009; 183:6681–6688. PMID: 19846875.

56. Wiersinga WM. Smoking and thyroid. Clin Endocrinol (Oxf). 2013; 79:145–151. PMID: 23581474.

57. Schmeltz LR, Blevins TC, Aronoff SL, Ozer K, Leffert JD, Goldberg MA, Horowitz BS, Bertenshaw RH, Troya P, Cohen AE, Lanier RK, Wright C 4th. Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto's) thyroiditis: a randomized controlled clinical trial. J Clin Endocrinol Metab. 2014; 99:E137–E142. PMID: 24178792.

58. Silva JE. The thermogenic effect of thyroid hormone and its clinical implications. Ann Intern Med. 2003; 139:205–213. PMID: 12899588.

59. Bechtold DA, Loudon AS. Hypothalamic thyroid hormones: mediators of seasonal physiology. Endocrinology. 2007; 148:3605–3607. PMID: 17639034.

60. Delange F, de Benoist B, Pretell E, Dunn JT. Iodine deficiency in the world: where do we stand at the turn of the century? Thyroid. 2001; 11:437–447. PMID: 11396702.