Int J Thyroidol.  2020 Nov;13(2):85-94. 10.11106/ijt.2020.13.2.85.

Recent Issues Related to Thyroid Disease in Pregnancy

• Chung JH

• KMID: 2509187
• DOI: http://doi.org/10.11106/ijt.2020.13.2.85

Abstract

Maternal and fetal complications may occur because of pathologic or immunologic changes during pregnancy. The American Thyroid Association (ATA) suggests an optimal thyroid stimulating hormone (TSH) reference range of 0.50-4.00 mU/L in pregnant women. Based on Korean data, the same range may be applied to Korean pregnant women. According to the ATA guideline, levothyroxine therapy is recommended for thyroid peroxidase antibody (TPOAb)-positive women with a TSH greater than the pregnancy-specific reference range (approximately ＞4.0 mU/L in Korea) and TPOAb-negative women with a TSH ＞10.0 mU/L. The presence of TPOAb may be a sign of hypothyroidism due to damage to the thyroid. Because the titer of TPOAb decreases as gestation progresses, its measurement should be performed as early as possible during pregnancy. Although the mechanism is unknown, the association between thyroid autoimmunity and miscarriage/premature delivery is clear. Selenium may reduce the development of postpartum thyroiditis and permanent hypothyroidism; however, routine prescription of selenium is not recommended as it may increase the risk of type 2 diabetes. According to Korean nationwide data, birth defects in antithyroid drug (ATD)-exposed offspring in early pregnancy increased by 1.1 to 2.2% compared with non-exposed offspring. Avoidance of ATD in early pregnancy is the best option, otherwise, it is preferable to switch to propylthiouracil before pregnancy. When methimazole use is unavoidable in early pregnancy, it is recommended to use less than 5 mg per day.

Keyword

Pregnancy; Thyrotropin; Autoantibodies; Antithyroid agents; Malformation

Reference

References

1. Glinoer D. 1997; The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 18(3):404–33. DOI: 10.1210/edrv.18.3.0300. PMID: 9183570.

2. Glinoer D. 2007; The importance of iodine nutrition during pregnancy. Public Health Nutr. 10(12A):1542–6. DOI: 10.1017/S1368980007360886. PMID: 18053277.

3. Glinoer D, De Nayer P, Delange F, Lemone M, Toppet V, Spehl M, et al. 1995; A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects. J Clin Endocrinol Metab. 80(1):258–69. DOI: 10.1210/jcem.80.1.7829623. PMID: 7829623.

4. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al. 2012; Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 97(8):2543–65. DOI: 10.1210/jc.2011-2803. PMID: 22869843.

5. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017; 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 27(3):315–89. DOI: 10.1089/thy.2016.0457. PMID: 28056690.

6. Orito Y, Oku H, Kubota S, Amino N, Shimogaki K, Hata M, et al. 2009; Thyroid function in early pregnancy in Japanese healthy women: relation to urinary iodine excretion, emesis, and fetal and child development. J Clin Endocrinol Metab. 94(5):1683–8. DOI: 10.1210/jc.2008-2111. PMID: 19258403.

7. Andersen S, Karmisholt J, Pedersen KM, Laurberg P. 2008; Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals. Br J Nutr. 99(4):813–8. DOI: 10.1017/S0007114507842292. PMID: 17961291.

8. Konig F, Andersson M, Hotz K, Aeberli I, Zimmermann MB. 2011; Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. J Nutr. 141(11):2049–54. DOI: 10.3945/jn.111.144071. PMID: 21918061.

9. Cho YY, Kim HJ, Oh SY, Choi SJ, Lee SY, Joung JY, et al. 2016; Iodine status in healthy pregnant women in Korea: a first report. Eur J Nutr. 55(2):469–75. DOI: 10.1007/s00394-015-0864-7. PMID: 25750059.

10. WHO. UNICEF. ICCIDD. 2007. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd ed. World Health Organization;Geneva:

11. Yi KH, Kim KW, Yim CH, Jung ED, Chung JH, Chung HK, et al. 2014; Guidelines for the diagnosis and management of thyroid disease during pregnancy and postpartum. J Korean Thyroid Assoc. 7(1):7–39. DOI: 10.11106/jkta.2014.7.1.7.

12. Vaidya B, Anthony S, Bilous M, Shields B, Drury J, Hutchison S, et al. 2007; Detection of thyroid dysfunction in early pregnancy: universal screening or targeted high-risk case finding? J Clin Endocrinol Metab. 92(1):203–7. DOI: 10.1210/jc.2006-1748. PMID: 17032713.

13. Horacek J, Spitalnikova S, Dlabalova B, Malirova E, Vizda J, Svilias I, et al. 2010; Universal screening detects two-times more thyroid disorders in early pregnancy than targeted high-risk case finding. Eur J Endocrinol. 163(4):645–50. DOI: 10.1530/EJE-10-0516. PMID: 20682632.

14. Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. 2010; Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab. 95(4):1699–707. DOI: 10.1210/jc.2009-2009. PMID: 20130074.

15. Laurberg P, Andersen SL, Pedersen IB, Andersen S, Carle A. 2013; Screening for overt thyroid disease in early pregnancy may be preferable to searching for small aberrations in thyroid function tests. Clin Endocrinol (Oxf). 79(3):297–304. DOI: 10.1111/cen.12232. PMID: 23627986.

16. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. 2011; Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 21(10):1081–125. DOI: 10.1089/thy.2011.0087. PMID: 21787128. PMCID: PMC3472679.

17. Li C, Shan Z, Mao J, Wang W, Xie X, Zhou W, et al. 2014; Assessment of thyroid function during first-trimester pregnancy: what is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women? J Clin Endocrinol Metab. 99(1):73–9. DOI: 10.1210/jc.2013-1674. PMID: 24276458.

18. Marwaha RK, Chopra S, Gopalakrishnan S, Sharma B, Kanwar RS, Sastry A, et al. 2008; Establishment of reference range for thyroid hormones in normal pregnant Indian women. BJOG. 115(5):602–6. DOI: 10.1111/j.1471-0528.2008.01673.x. PMID: 18333941.

19. Moon HW, Chung HJ, Park CM, Hur M, Yun YM. 2015; Establishment of trimester-specific reference intervals for thyroid hormones in Korean pregnant women. Ann Lab Med. 35(2):198–204. DOI: 10.3343/alm.2015.35.2.198. PMID: 25729721. PMCID: PMC4330169.

20. Kim HJ, Cho YY, Kim SW, Kim TH, Jang HW, Lee SY, et al. 2018; Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area. Korean J Intern Med. 33(3):552–60. DOI: 10.3904/kjim.2016.051. PMID: 28171716. PMCID: PMC5943647.

21. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. 2002; 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. 87(2):489–99. DOI: 10.1210/jcem.87.2.8182. PMID: 11836274.

22. Kim WG, Kim WB, Woo G, Kim H, Cho Y, Kim TY, et al. 2017; Thyroid stimulating hormone reference range and prevalence of thyroid dysfunction in the Korean population: Korea National Health and Nutrition Examination Survey 2013 to 2015. Endocrinol Metab (Seoul). 32(1):106–14. DOI: 10.3803/EnM.2017.32.1.106. PMID: 28116874. PMCID: PMC5368108.

23. Stagnaro-Green A, Roman SH, Cobin RH, Wallenstein S, Davies TF. el-Harazy E. 1992; A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction. J Clin Endocrinol Metab. 74(3):645–53. DOI: 10.1210/jcem.74.3.1740500. PMID: 1740500.

24. Shi X, Han C, Li C, Mao J, Wang W, Xie X, et al. 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):1630–8. DOI: 10.1210/jc.2014-3704. PMID: 25629356.

25. Glinoer D, Riahi M, Grun JP, Kinthaert J. 1994; Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab. 79(1):197–204. DOI: 10.1210/jcem.79.1.8027226. PMID: 8027226.

26. Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. 2006; Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab. 91(7):2587–91. DOI: 10.1210/jc.2005-1603. PMID: 16621910.

27. Medici M, de Rijke YB, Peeters RP, Visser W, de Muinck Keizer-Schrama SM, Jaddoe VV, et al. 2012; Maternal early pregnancy and newborn thyroid hormone parameters: the Generation R study. J Clin Endocrinol Metab. 97(2):646–52. DOI: 10.1210/jc.2011-2398. PMID: 22162477.

28. De Leo S, Pearce EN. 2018; Autoimmune thyroid disease during pregnancy. Lancet Diabetes Endocrinol. 6(7):575–86. DOI: 10.1016/S2213-8587(17)30402-3. PMID: 29246752.

29. Liu H, Shan Z, Li C, Mao J, Xie X, Wang W, et al. 2014; Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study. Thyroid. 24(11):1642–9. DOI: 10.1089/thy.2014.0029. PMID: 25087688. PMCID: PMC4229690.

30. Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. 1990; Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 264(11):1422–5. DOI: 10.1001/jama.1990.03450110068029. PMID: 2118190.

31. Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. 2011; Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 342:d2616. DOI: 10.1136/bmj.d2616. PMID: 21558126. PMCID: PMC3089879.

32. van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, et al. 2011; Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum Reprod Update. 17(5):605–19. DOI: 10.1093/humupd/dmr024. PMID: 21622978.

33. Mecacci F, Parretti E, Cioni R, Lucchetti R, Magrini A, La Torre P, et al. 2000; Thyroid autoimmunity and its association with non-organ-specific antibodies and subclinical alterations of thyroid function in women with a history of pregnancy loss or preeclampsia. J Reprod Immunol. 46(1):39–50. DOI: 10.1016/S0165-0378(99)00055-8.

34. Kim NY, Cho HJ, Kim HY, Yang KM, Ahn HK, Thornton S, et al. 2011; Thyroid autoimmunity and its association with cellular and humoral immunity in women with reproductive failures. Am J Reprod Immunol. 65(1):78–87. DOI: 10.1111/j.1600-0897.2010.00911.x. PMID: 20712806.

35. Kwak-Kim JY, Chung-Bang HS, Ng SC, Ntrivalas EI, Mangubat CP, Beaman KD, et al. 2003; Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod. 18(4):767–73. DOI: 10.1093/humrep/deg156. PMID: 12660269.

36. Konova E. 2010; The role of NK cells in the autoimmune thyroid disease-associated pregnancy loss. Clin Rev Allergy Immunol. 39(3):176–84. DOI: 10.1007/s12016-010-8201-7. PMID: 20237962.

37. Toulis KA, Goulis DG, Venetis CA, Kolibianakis EM, Tarlatzis BC, Papadimas I. 2009; Thyroid autoimmunity and miscarriages: the corpus luteum hypothesis. Med Hypotheses. 73(6):1060–2. DOI: 10.1016/j.mehy.2009.05.012. PMID: 19505771.

38. Lepoutre T, Debieve F, Gruson D, Daumerie C. 2012; Reduction of miscarriages through universal screening and treatment of thyroid autoimmune diseases. Gynecol Obstet Invest. 74(4):265–73. DOI: 10.1159/000343759. PMID: 23147711.

39. Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K, Farrell-Carver S, et al. 2019; Levothyroxine in women with thyroid peroxidase antibodies before conception. N Engl J Med. 380(14):1316–25. DOI: 10.1056/NEJMoa1812537. PMID: 30907987.

40. Vissenberg R, van Dijk MM, Fliers E, van der Post JAM, van Wely M, Bloemenkamp KWM, et al. 2015; Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study). Contemp Clin Trials. 44:134–8. DOI: 10.1016/j.cct.2015.08.005. PMID: 26255238.

41. Stagnaro-Green A, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Negro R. 2011; High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy. J Clin Endocrinol Metab. 96(3):652–7. DOI: 10.1210/jc.2010-1980. PMID: 21190974.

42. Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. 2007; The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 92(4):1263–8. DOI: 10.1210/jc.2006-1821. PMID: 17284630.

43. Mao J, Pop VJ, Bath SC, Vader HL, Redman CW, Rayman MP. 2016; Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency. Eur J Nutr. 55(1):55–61. DOI: 10.1007/s00394-014-0822-9. PMID: 25524327. PMCID: PMC4737786.

44. Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, et al. 2007; Effects of long-term selenium supplemen-tation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 147(4):217–23. DOI: 10.7326/0003-4819-147-4-200708210-00175. PMID: 17620655.

45. Rivkees SA, Mattison DR. 2009; Ending propylthiouracil-induced liver failure in children. N Engl J Med. 360(15):1574–5. DOI: 10.1056/NEJMc0809750. PMID: 19357418.

46. Bahn RS, Burch HS, Cooper DS, Garber JR, Greenlee CM, Klein IL, et al. 2009; The role of propylthiouracil in the management of Graves' disease in adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid. 19(7):673–4. DOI: 10.1089/thy.2009.0169. PMID: 19583480.

47. Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. 2011; Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 21(6):593–646. DOI: 10.1089/thy.2010.0417. PMID: 21510801.

48. Andersen SL, Olsen J, Wu CS, Laurberg P. 2013; Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J Clin Endocrinol Metab. 98(11):4373–81. DOI: 10.1210/jc.2013-2831. PMID: 24151287.

49. Seo GH, Kim TH, Chung JH. 2018; Antithyroid drugs and congenital malformations: a nationwide Korean cohort study. Ann Intern Med. 168(6):405–13. DOI: 10.7326/M17-1398. PMID: 29357398.