Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Assessment and treatment of thyroid disorders in pregnancy and the postpartum period

Nature Reviews Endocrinology volume 18, pages 158–171 (2022)Cite this article

Subjects

Abstract

Thyroid disorders are prevalent in pregnant women. Furthermore, thyroid hormone has a critical role in fetal development and thyroid dysfunction can adversely affect obstetric outcomes. Thus, the appropriate management of hyperthyroidism, most commonly caused by Graves disease, and hypothyroidism, which in iodine sufficient regions is most commonly caused by Hashimoto thyroiditis, in pregnancy is important for the health of both pregnant women and their offspring. Gestational transient thyrotoxicosis can also occur during pregnancy and should be differentiated from Graves disease. Effects of thyroid autoimmunity and subclinical hypothyroidism in pregnancy remain controversial. Iodine deficiency is the leading cause of hypothyroidism worldwide. Despite global efforts to eradicate iodine deficiency disorders, pregnant women remain at risk of iodine deficiency due to increased iodine requirements during gestation. The incidence of thyroid cancer is increasing worldwide, including in young adults. As such, the diagnosis of thyroid nodules or thyroid cancer during pregnancy is becoming more frequent. The evaluation and management of thyroid nodules and thyroid cancer in pregnancy pose a particular challenge. Postpartum thyroiditis can occur up to 1 year after delivery and must be differentiated from other forms of thyroid dysfunction, as treatment differs. This Review provides current evidence and recommendations for the evaluation and management of thyroid disorders in pregnancy and in the postpartum period.

Key points

  • Serum levels of thyroid stimulating hormone might be lower in pregnant women during early gestation than levels outside the pregnancy setting, due to increased production of thyroid hormone and stimulation from high levels of human chorionic gonadotropin.

  • Levothyroxine treatment for maternal subclinical hypothyroidism in pregnancy remains controversial because currently available studies have not shown a clear benefit of treatment on obstetric or child neurodevelopmental outcomes.

  • Treatment of Graves disease in pregnancy requires careful consideration of the adverse effects of uncontrolled hyperthyroidism, antithyroid drugs and overtreatment of hyperthyroidism on pregnancy outcomes.

  • Women who are planning to be pregnant, are pregnant or are breastfeeding should take a daily oral supplement containing 150 µg of iodine to prevent adverse effects of iodine deficiency.

  • Treatment of differentiated thyroid cancer diagnosed in pregnancy can be safely deferred until after pregnancy with close monitoring for any tumour size increase or spread during pregnancy.

  • Postpartum thyroiditis is a destructive thyroiditis that typically presents with thyrotoxicosis followed by transient hypothyroidism up to the first 12 months after childbirth.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Factors increasing maternal dietary iodine requirement in pregnancy.
Fig. 2: Time course of postpartum thyroiditis.

Similar content being viewed by others

Article 19 May 2022

Layal Chaker, Salman Razvi, … Robin P. Peeters

References

  1. Taylor, P. N. et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat. Rev. Endocrinol. 14, 301–316 (2018).

    Article  PubMed  Google Scholar 

  2. Dong, A. C. & Stagnaro-Green, A. Differences in diagnostic criteria mask the true prevalence of thyroid disease in pregnancy: a systematic review and meta-analysis. Thyroid 29, 278–289 (2019).

    Article  PubMed  Google Scholar 

  3. Burrow, G. N., Fisher, D. A. & Larsen, P. R. Maternal and fetal thyroid function. N. Engl. J. Med. 331, 1072–1078 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. Stagnaro-Green, A. Approach to the patient with postpartum thyroiditis. J. Clin. Endocrinol. Metab. 97, 334–342 (2012).

    Article  CAS  PubMed  Google Scholar 

  5. Yoshimura, M. & Hershman, J. M. Thyrotropic action of human chorionic gonadotropin. Thyroid 5, 425–434 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Alexander, E. K. et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 27, 315–389 (2017). This paper describes the most current ATA guideline on diagnosis and management of thyroid disease in pregnancy and the postpartum period.

    Article  PubMed  Google Scholar 

  7. Ollero, M. D. et al. Thyroid function reference values in healthy iodine-sufficient pregnant women and influence of thyroid nodules on thyrotropin and free thyroxine values. Thyroid 29, 421–429 (2019).

    Article  CAS  PubMed  Google Scholar 

  8. Lim, H., Devesa, S. S., Sosa, J. A., Check, D. & Kitahara, C. M. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA 317, 1338–1348 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kim, J., Gosnell, J. E. & Roman, S. A. Geographic influences in the global rise of thyroid cancer. Nat. Rev. Endocrinol. 16, 17–29 (2020).

    Article  PubMed  Google Scholar 

  10. Miller, K. D. et al. Cancer statistics for adolescents and young adults, 2020. CA Cancer J. Clin. 70, 443–459 (2020).

    Article  PubMed  Google Scholar 

  11. Glinoer, D. et al. Regulation of maternal thyroid during pregnancy. J. Clin. Endocrinol. Metab. 71, 276–287 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. Li, C. et al. 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, 73–79 (2014).

    Article  CAS  PubMed  Google Scholar 

  13. [No authors listed] Thyroid disease in pregnancy: ACOG Practice Bulletin, Number 223. Obstet. Gynecol. 135, e261–e274 (2020). This paper describes the most recent ACOG recommendations on the diagnosis and management of thyroid disease in pregnancy.

    Article  Google Scholar 

  14. Krassas, G. E., Poppe, K. & Glinoer, D. Thyroid function and human reproductive health. Endocr. Rev. 31, 702–755 (2010). This is a comprehensive review on the interactions between thyroid function and human reproduction.

    Article  CAS  PubMed  Google Scholar 

  15. Lee, R. H. et al. Free T4 immunoassays are flawed during pregnancy. Am. J. Obstet. Gynecol. 200, 260.e1–250.e6 (2009).

    Article  Google Scholar 

  16. Gronowski, A. M. Evaluation of thyroid function during pregnancy: have we taken a wrong turn? Clin. Chem. 64, 439–441 (2018).

    Article  CAS  PubMed  Google Scholar 

  17. Hernández, J. M. et al. Reference intervals of thyroid function tests assessed by immunoassay and mass spectrometry in healthy pregnant women living in Catalonia. J. Clin. Med. 10, 2444 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Weeke, J. et al. A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy. Acta Endocrinol. 101, 531–537 (1982).

    Article  CAS  Google Scholar 

  19. Davis, L. E., Leveno, K. J. & Cunningham, F. G. Hypothyroidism complicating pregnancy. Obstet. Gynecol. 72, 108–112 (1988).

    CAS  PubMed  Google Scholar 

  20. Leung, A. S., Millar, L. K., Koonings, P. P., Montoro, M. & Mestman, J. H. Perinatal outcome in hypothyroid pregnancies. Obstet. Gynecol. 81, 349–353 (1993).

    CAS  PubMed  Google Scholar 

  21. Männistö, T. et al. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J. Clin. Endocrinol. Metab. 98, 2725–2733 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Howdeshell, K. L. A model of the development of the brain as a construct of the thyroid system. Environ. Health Perspect. 110, 337–348 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bernal, J., Guadaño-Ferraz, A. & Morte, B. Perspectives in the study of thyroid hormone action on brain development and function. Thyroid 13, 1005–1012 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Moog, N. K. et al. Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience 342, 68–100 (2017).

    Article  CAS  PubMed  Google Scholar 

  25. de Escobar, G. M., Obregón, M. J. & del Rey, F. E. Maternal thyroid hormones early in pregnancy and fetal brain development. Best. Pract. Res. Clin. Endocrinol. Metab. 18, 225–248 (2004).

    Article  PubMed  Google Scholar 

  26. Man, E. B., Jones, W. S., Holden, R. H. & Mellits, E. D. Thyroid function in human pregnancy. 8. Retardation of progeny aged 7 years; relationships to maternal age and maternal thyroid function. Am. J. Obstet. Gynecol. 111, 905–916 (1971).

    Article  CAS  PubMed  Google Scholar 

  27. Man, E. B. & Serunian, S. A. Thyroid function in human pregnancy. IX. Development or retardation of 7-year-old progeny of hypothyroxinemic women. Am. J. Obstet. Gynecol. 125, 949 (1976).

    Article  CAS  PubMed  Google Scholar 

  28. Haddow, J. E. et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N. Engl. J. Med. 341, 549–555 (1999).

    Article  CAS  PubMed  Google Scholar 

  29. Cleary-Goldman, J. et al. Maternal thyroid hypofunction and pregnancy outcome. Obstet. Gynecol. 112, 85–92 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Männistö, T. et al. Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective population-based cohort study. J. Clin. Endocrinol. Metab. 94, 772–779 (2009).

    Article  PubMed  Google Scholar 

  31. Männistö, T. et al. Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life. J. Clin. Endocrinol. Metab. 95, 1084–1094 (2010).

    Article  PubMed  Google Scholar 

  32. Sheehan, P. M., Nankervis, A., Araujo Júnior, E. & Da Silva Costa, F. Maternal thyroid disease and preterm birth: systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 100, 4325–4331 (2015).

    Article  CAS  PubMed  Google Scholar 

  33. Negro, R. et al. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J. Clin. Endocrinol. Metab. 95, E44–E48 (2010).

    Article  PubMed  Google Scholar 

  34. Liu, H. et al. Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study. Thyroid 24, 1642–1649 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Casey, B. M. et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet. Gynecol. 105, 239–245 (2005).

    Article  PubMed  Google Scholar 

  36. Korevaar, T. I. M. et al. Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the generation R study. J. Clin. Endocrinol. Metab. 98, 4382–4390 (2013).

    Article  CAS  PubMed  Google Scholar 

  37. Maraka, S. et al. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid 26, 580–590 (2016). This systematic review and meta-analysis summarizes results of randomized trials and cohort studies on the effects of subclinical hypothyroidism in pregnancy published up to 2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lee, S. Y., Cabral, H. J., Aschengrau, A. & Pearce, E. N. Associations between maternal thyroid function in pregnancy and obstetric and perinatal outcomes. J. Clin. Endocrinol. Metab. 105, e2015–e2023 (2020).

    Article  Google Scholar 

  39. Consortium on Thyroid and Pregnancy — Study Group on Preterm Birth. et al. Association of thyroid function test abnormalities and thyroid autoimmunity with preterm birth: a systematic review and meta-analysis. JAMA 322, 632–641 (2019). This study assesses risk of preterm birth associated with maternal thyroid hypofunction and thyroid autoimmunity using individual data from 47,045 pregnant women from 19 cohort studies.

    Article  Google Scholar 

  40. Ramezani Tehrani, F., Nazarpour, S. & Behboudi-Gandevani, S. Isolated maternal hypothyroxinemia and adverse pregnancy outcomes: a systematic review. J. Gynecol. Obstet. Hum. Reprod. 50, 102057 (2021).

    Article  PubMed  Google Scholar 

  41. Korevaar, T. I. M. et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol. 4, 35–43 (2016).

    Article  CAS  PubMed  Google Scholar 

  42. Jansen, T. A. et al. Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort. Lancet Diabetes Endocrinol. 7, 629–637 (2019). This study assessed offspring brain morphology by MRI at a median age of 10 years in 1,981 mother–child pairs with maternal thyroid function measurements during pregnancy.

    Article  CAS  PubMed  Google Scholar 

  43. Nelson, S. M. et al. Maternal thyroid function and child educational attainment: prospective cohort study. BMJ 360, k452 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Thompson, W. et al. Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: a systematic review and meta-analysis. Clin. Endocrinol. 88, 575–584 (2018).

    Article  CAS  Google Scholar 

  45. Yamamoto, J. M., Benham, J. L., Nerenberg, K. A. & Donovan, L. E. Impact of levothyroxine therapy on obstetric, neonatal and childhood outcomes in women with subclinical hypothyroidism diagnosed in pregnancy: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 8, e022837 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Nazarpour, S. et al. Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. J. Clin. Endocrinol. Metab. 103, 926–935 (2018).

    Article  PubMed  Google Scholar 

  47. Nazarpour, S., Ramezani Tehrani, F., Amiri, M., Bidhendi Yarandi, R. & Azizi, F. Levothyroxine treatment and pregnancy outcomes in women with subclinical hypothyroidism: a systematic review and meta-analysis. Arch. Gynecol. Obstet. 300, 805–819 (2019). This systematic review and meta-analysis summarizes results of 13 randomized controlled trials and cohort studies on the effects of levothyroxine treatment for maternal subclinical hypothyroidism on pregnancy outcomes.

    Article  CAS  PubMed  Google Scholar 

  48. Casey, B. M. et al. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N. Engl. J. Med. 376, 815–825 (2017). This US randomized controlled trial assessed the effects of levothyroxine treatment of maternal thyroid hypofunction on pregnancy outcomes and child neurodevelopmental outcomes at a median age of 5 years.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lazarus, J. H. et al. Antenatal thyroid screening and childhood cognitive function. N. Engl. J. Med. 366, 493–501 (2012). This UK randomized controlled trial assessed the effects of levothyroxine treatment of maternal thyroid hypofunction on child neurodevelopmental outcomes at 3 years of age.

    Article  CAS  PubMed  Google Scholar 

  50. Hales, C. et al. Controlled antenatal thyroid screening II: effect of treating maternal suboptimal thyroid function on child cognition. J. Clin. Endocrinol. Metab. 103, 1583–1591 (2018).

    Article  PubMed  Google Scholar 

  51. De Leo, S. & Pearce, E. N. Autoimmune thyroid disease during pregnancy. Lancet Diabetes Endocrinol. 6, 575–586 (2018).

    Article  PubMed  Google Scholar 

  52. Thangaratinam, S. et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 342, d2616 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Xie, J. et al. Effect of antithyroid antibodies on women with recurrent miscarriage: a meta-analysis. Am. J. Reprod. Immunol. 83, e13238 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Glinoer, D., Riahi, M., Grün, J. P. & Kinthaert, J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J. Clin. Endocrinol. Metab. 79, 197–204 (1994).

    CAS  PubMed  Google Scholar 

  55. Korevaar, T. I. M. et al. Thyroid autoimmunity impairs the thyroidal response to human chorionic gonadotropin: two population-based prospective cohort studies. J. Clin. Endocrinol. Metab. 102, 69–77 (2017). This cohort study showed a suboptimal thyroidal response to hCG stimulation in pregnant women with positive TPO antibody status.

    PubMed  Google Scholar 

  56. Negro, R., Schwartz, A. & Stagnaro-Green, A. Impact of levothyroxine in miscarriage and preterm delivery rates in first trimester thyroid antibody-positive women with TSH less than 2.5 mIU/L. J. Clin. Endocrinol. Metab. 101, 3685–3690 (2016).

    Article  CAS  PubMed  Google Scholar 

  57. Nazarpour, S. et al. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. Eur. J. Endocrinol. 176, 253–265 (2017).

    Article  CAS  PubMed  Google Scholar 

  58. Wang, H. et al. Effect of levothyroxine on miscarriage among women with normal thyroid function and thyroid autoimmunity undergoing in vitro fertilization and embryo transfer: a randomized clinical trial. JAMA 318, 2190–2198 (2017).

    Article  CAS  PubMed  Google Scholar 

  59. Dhillon-Smith, R. K. et al. Levothyroxine in women with thyroid peroxidase antibodies before conception. N. Engl. J. Med. 380, 1316–1325 (2019). This UK randomized controlled trial assessed the effects of levothyroxine treatment starting preconception for euthyroid women with positive TPO antibodies and a history of miscarriage or infertility on live birth rates.

    Article  CAS  PubMed  Google Scholar 

  60. Lau, L., Benham, J. L., Lemieux, P., Yamamoto, J. & Donovan, L. E. Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 11, e043751 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Lazarus, J. et al. 2014 European Thyroid Association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur. Thyroid. J. 3, 76–94 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Practice Committee of the American Society for Reproductive Medicine. Subclinical hypothyroidism in the infertile female population: a guideline. Fertil. Steril. 104, 545–553 (2015).

    Article  Google Scholar 

  63. Sitoris, G. et al. Screening for thyroid dysfunction in pregnancy with targeted high-risk case finding: can it be improved? J. Clin. Endocrinol. Metab. 104, 2346–2354 (2019).

    Article  PubMed  Google Scholar 

  64. Pop, V. J., Broeren, M. A., Wiersinga, W. M. & Stagnaro-Green, A. Thyroid disease symptoms during early pregnancy do not identify women with thyroid hypofunction that should be treated. Clin. Endocrinol. 87, 838–843 (2017).

    Article  CAS  Google Scholar 

  65. Rosario, P. W. Selective screening for thyroid dysfunction in pregnant women: how often do low-risk women cease to be treated following the new guidelines of the American Thyroid Association? Arch. Endocrinol. Metab. 62, 641–643 (2018).

    Article  PubMed  Google Scholar 

  66. Jouyandeh, Z., Hasani-Ranjbar, S., Qorbani, M. & Larijani, B. Universal screening versus selective case-based screening for thyroid disorders in pregnancy. Endocrine 48, 116–123 (2015).

    Article  CAS  PubMed  Google Scholar 

  67. Calvo, R., Obregón, M. J., Ruiz de Oña, C., Escobar del Rey, F. & Morreale de Escobar, G. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3′-triiodothyronine in the protection of the fetal brain. J. Clin. Invest. 86, 889–899 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Arafah, B. M. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N. Engl. J. Med. 344, 1743–1749 (2001).

    Article  CAS  PubMed  Google Scholar 

  69. Yassa, L., Marqusee, E., Fawcett, R. & Alexander, E. K. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J. Clin. Endocrinol. Metab. 95, 3234–3241 (2010).

    Article  CAS  PubMed  Google Scholar 

  70. Cooper, D. S. & Laurberg, P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol. 1, 238–249 (2013).

    Article  CAS  PubMed  Google Scholar 

  71. Glinoer, D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr. Rev. 18, 404–433 (1997).

    Article  CAS  PubMed  Google Scholar 

  72. Yeo, C. P. et al. Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to 14th weeks of pregnancy: correlations with total and free beta human chorionic gonadotrophin. Clin. Endocrinol. 55, 391–398 (2001).

    Article  CAS  Google Scholar 

  73. Andersen, S. L., Olsen, J., Carlé, A. & Laurberg, P. Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance with some other autoimmune diseases: a Danish population-based study. J. Clin. Endocrinol. Metab. 100, 1164–1171 (2015).

    Article  CAS  PubMed  Google Scholar 

  74. Laurberg, P. & Andersen, S. L. Endocrinology in pregnancy: pregnancy and the incidence, diagnosing and therapy of Graves’ disease. Eur. J. Endocrinol. 175, R219–R230 (2016).

    Article  CAS  PubMed  Google Scholar 

  75. Goodwin, T. M., Montoro, M., Mestman, J. H., Pekary, A. E. & Hershman, J. M. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J. Clin. Endocrinol. Metab. 75, 1333–1337 (1992).

    CAS  PubMed  Google Scholar 

  76. Goodwin, T. M., Montoro, M. & Mestman, J. H. Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am. J. Obstet. Gynecol. 167, 648–652 (1992).

    Article  CAS  PubMed  Google Scholar 

  77. Kahaly, G. J., Diana, T. & Olivo, P. D. TSH receptor antibodies: relevance & utility. Endocr. Pract. 26, 97–106 (2020).

    Article  PubMed  Google Scholar 

  78. Bouillon, R. et al. Thyroid function in patients with hyperemesis gravidarum. Am. J. Obstet. Gynecol. 143, 922–926 (1982).

    Article  CAS  PubMed  Google Scholar 

  79. Kinomoto-Kondo, S. et al. The effects of gestational transient thyrotoxicosis on the perinatal outcomes: a case-control study. Arch. Gynecol. Obstet. 295, 87–93 (2017).

    Article  PubMed  Google Scholar 

  80. Sheffield, J. S. & Cunningham, F. G. Thyrotoxicosis and heart failure that complicate pregnancy. Am. J. Obstet. Gynecol. 190, 211–217 (2004).

    Article  PubMed  Google Scholar 

  81. Millar, L. K. et al. Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism. Obstet. Gynecol. 84, 946–949 (1994).

    CAS  PubMed  Google Scholar 

  82. Casey, B. M. et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet. Gynecol. 107, 337–341 (2006).

    Article  PubMed  Google Scholar 

  83. Scappaticcio, L. et al. Abnormal liver blood tests in patients with hyperthyroidism: systematic review and meta-analysis. Thyroid 31, 884–894 (2021).

    Article  CAS  PubMed  Google Scholar 

  84. Suzuki, N. et al. Analysis of antithyroid drug-induced severe liver injury in 18,558 newly diagnosed patients with Graves’ disease in Japan. Thyroid 29, 1390–1398 (2019).

    Article  CAS  PubMed  Google Scholar 

  85. Yu, W. et al. Side effects of PTU and MMI in the treatment of hyperthyroidism: a systematic review and meta-analysis. Endocr. Pract. 26, 207–217 (2020).

    Article  PubMed  Google Scholar 

  86. Rivkees, S. A. & Szarfman, A. Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children. J. Clin. Endocrinol. Metab. 95, 3260–3267 (2010).

    Article  CAS  PubMed  Google Scholar 

  87. Cooper, D. S. & Rivkees, S. A. Putting propylthiouracil in perspective. J. Clin. Endocrinol. Metab. 94, 1881–1882 (2009).

    Article  CAS  PubMed  Google Scholar 

  88. Andersen, S. L., Olsen, J., Wu, C. S. & Laurberg, P. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J. Clin. Endocrinol. Metab. 98, 4373–4381 (2013).

    Article  CAS  PubMed  Google Scholar 

  89. Andersen, S. L., Olsen, J., Wu, C. S. & Laurberg, P. Severity of birth defects after propylthiouracil exposure in early pregnancy. Thyroid 24, 1533–1540 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Andersen, S. L., Lönn, S., Vestergaard, P. & Törring, O. Birth defects after use of antithyroid drugs in early pregnancy: a Swedish nationwide study. Eur. J. Endocrinol. 177, 369–378 (2017).

    Article  CAS  PubMed  Google Scholar 

  91. Seo, G. H., Kim, T. H. & Chung, J. H. Antithyroid drugs and congenital malformations: a nationwide Korean cohort study. Ann. Intern. Med. 168, 405–413 (2018).

    Article  PubMed  Google Scholar 

  92. Andersen, S. L., Knøsgaard, L., Olsen, J., Vestergaard, P. & Andersen, S. Maternal thyroid function, use of antithyroid drugs in early pregnancy, and birth defects. J. Clin. Endocrinol. Metab. 104, 6040–6048 (2019). This large study assessed the effects of antithyroid drug use in early pregnancy on risk of birth defects utilizing the Danish national registry.

    Article  PubMed  Google Scholar 

  93. Momotani, N., Noh, J. Y., Ishikawa, N. & Ito, K. Effects of propylthiouracil and methimazole on fetal thyroid status in mothers with Graves’ hyperthyroidism. J. Clin. Endocrinol. Metab. 82, 3633–3636 (1997).

    CAS  PubMed  Google Scholar 

  94. Laurberg, P. et al. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur. J. Endocrinol. 158, 69–75 (2008).

    Article  CAS  PubMed  Google Scholar 

  95. American Thyroid Association Taskforce on Radioiodine Safety. et al. Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I: practice recommendations of the American Thyroid Association. Thyroid 21, 335–346 (2011).

    Article  Google Scholar 

  96. Leung, A. M., Pearce, E. N. & Braverman, L. E. Iodine nutrition in pregnancy and lactation. Endocrinol. Metab. Clin. North Am. 40, 765–777 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (National Academies Press (US), 2001).

  98. WHO Secretariat, Andersson, M., de Benoist, B., Delange, F. & Zupan, J. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation. Public Health Nutr. 10, 1606–1611 (2007). This documents reviews recommendations regarding iodine intake in pregnant and lactating women and children to prevent iodine deficiency.

    Article  Google Scholar 

  99. WHO, UNICEF, ICCIDD. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd ed. http://whqlibdoc.who.int/publications/2007/9789241595827_eng.pdf (2007).

  100. Andersen, S., Karmisholt, J., Pedersen, K. M. & Laurberg, P. Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals. Br. J. Nutr. 99, 813–818 (2008).

    Article  CAS  PubMed  Google Scholar 

  101. Pearce, E. N. & Caldwell, K. L. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status. Am. J. Clin. Nutr. 104, 898S–901S (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wong, E. M., Sullivan, K. M., Perrine, C. G., Rogers, L. M. & Peña-Rosas, J. P. Comparison of median urinary iodine concentration as an indicator of iodine status among pregnant women, school-age children, and nonpregnant women. Food Nutr. Bull. 32, 206–212 (2011).

    Article  PubMed  Google Scholar 

  103. Zimmermann, M. B., Gizak, M., Abbott, K., Andersson, M. & Lazarus, J. H. Iodine deficiency in pregnant women in Europe. Lancet Diabetes Endocrinol. 3, 672–674 (2015).

    Article  PubMed  Google Scholar 

  104. Caldwell, K. L. et al. Iodine status in pregnant women in the National Children’s Study and in U.S. women (15-44 years), National Health and Nutrition Examination Survey 2005-2010. Thyroid 23, 927–937 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Perrine, C. G., Herrick, K. A., Gupta, P. M. & Caldwell, K. L. Iodine status of pregnant women and women of reproductive age in the United States. Thyroid 29, 153–154 (2019).

    Article  PubMed  Google Scholar 

  106. Caldwell, K. L., Makhmudov, A., Ely, E., Jones, R. L. & Wang, R. Y. Iodine status of the U.S. population, National Health and Nutrition Examination Survey, 2005–2006 and 2007–2008. Thyroid 21, 419–427 (2011).

    Article  PubMed  Google Scholar 

  107. Caldwell, K. L., Miller, G. A., Wang, R. Y., Jain, R. B. & Jones, R. L. Iodine status of the U.S. population, National Health and Nutrition Examination Survey 2003-2004. Thyroid 18, 1207–1214 (2008).

    Article  CAS  PubMed  Google Scholar 

  108. Yarrington, C. & Pearce, E. N. Iodine and pregnancy. J. Thyroid Res. 2011, 934104 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Abuye, C. & Berhane, Y. The goitre rate, its association with reproductive failure, and the knowledge of iodine deficiency disorders (IDD) among women in Ethiopia: cross-section community based study. BMC Public Health 7, 316 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Pearce, E. N. Effects of iodine deficiency in pregnancy. J. Trace Elem. Med. Biol. 26, 131–133 (2012).

    Article  CAS  PubMed  Google Scholar 

  111. Glinoer, D. The importance of iodine nutrition during pregnancy. Public Health Nutr. 10, 1542–1546 (2007).

    Article  PubMed  Google Scholar 

  112. Pharoah, P. O., Ellis, S. M., Ekins, R. P. & Williams, E. S. Maternal thyroid function, iodine deficiency and fetal development. Clin. Endocrinol. 5, 159–166 (1976).

    Article  CAS  Google Scholar 

  113. Pharoah, P. O., Buttfield, I. H. & Hetzel, B. S. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet 1, 308–310 (1971).

    Article  CAS  PubMed  Google Scholar 

  114. Bougma, K., Aboud, F. E., Harding, K. B. & Marquis, G. S. Iodine and mental development of children 5 years old and under: a systematic review and meta-analysis. Nutrients 5, 1384–1416 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Qian, M. et al. The effects of iodine on intelligence in children: a meta-analysis of studies conducted in China. Asia Pac. J. Clin. Nutr. 14, 32–42 (2005).

    CAS  PubMed  Google Scholar 

  116. Jiskra, J. et al. Mild iodine deficiency in women after spontaneous abortions living in an iodine-sufficient area of Czech Republic: prevalence and impact on reproductive health. Clin. Endocrinol. 80, 452–458 (2014).

    Article  CAS  Google Scholar 

  117. Charoenratana, C., Leelapat, P., Traisrisilp, K. & Tongsong, T. Maternal iodine insufficiency and adverse pregnancy outcomes. Matern. Child Nutr. 12, 680–687 (2016).

    Article  PubMed  Google Scholar 

  118. Abel, M. H. et al. Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian Mother, Father and Child Cohort Study. BMC Med. 18, 211 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Gargari, S. S. et al. Maternal and neonatal outcomes and determinants of iodine deficiency in third trimester of pregnancy in an iodine sufficient area. BMC Pregnancy Childbirth 20, 174 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Torlinska, B., Bath, S. C., Janjua, A., Boelaert, K. & Chan, S.-Y. Iodine status during pregnancy in a region of mild-to-moderate iodine deficiency is not associated with adverse obstetric outcomes; results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Nutrients 10, 291 (2018).

    Article  PubMed Central  Google Scholar 

  121. Bath, S. C., Steer, C. D., Golding, J., Emmett, P. & Rayman, M. P. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet 382, 331–337 (2013).

    Article  CAS  PubMed  Google Scholar 

  122. Hynes, K. L., Otahal, P., Hay, I. & Burgess, J. R. Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort. J. Clin. Endocrinol. Metab. 98, 1954–1962 (2013).

    Article  CAS  PubMed  Google Scholar 

  123. Mil, N. H. V. et al. Low urinary iodine excretion during early pregnancy is associated with alterations in executive functioning in children. J. Nutr. 142, 2167–2174 (2012).

    Article  PubMed  Google Scholar 

  124. Costeira, M. J. et al. Psychomotor development of children from an iodine-deficient region. J. Pediatr. 159, 447–453 (2011).

    Article  PubMed  Google Scholar 

  125. Moleti, M. et al. Effects of maternal iodine nutrition and thyroid status on cognitive development in offspring: a pilot study. Thyroid 26, 296–305 (2016).

    Article  CAS  PubMed  Google Scholar 

  126. Zhou, S. J. et al. Association between maternal iodine intake in pregnancy and childhood neurodevelopment at age 18 months. Am. J. Epidemiol. 188, 332–338 (2019).

    Article  PubMed  Google Scholar 

  127. Levie, D. et al. Association of maternal iodine status with child IQ: a meta-analysis of individual participant data. J. Clin. Endocrinol. Metab. 104, 5957–5967 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Ghassabian, A. et al. Maternal urinary iodine concentration in pregnancy and children’s cognition: results from a population-based birth cohort in an iodine-sufficient area. BMJ Open 4, e005520 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Nazeri, P., Shariat, M. & Azizi, F. Effects of iodine supplementation during pregnancy on pregnant women and their offspring: a systematic review and meta-analysis of trials over the past 3 decades. Eur. J. Endocrinol. 184, 91–106 (2021).

    Article  CAS  PubMed  Google Scholar 

  130. Dineva, M., Fishpool, H., Rayman, M. P., Mendis, J. & Bath, S. C. Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women. Am. J. Clin. Nutr. 112, 389–412 (2020). This systematic review and meta-analysis summarizes findings of 37 randomized controlled trials, intervention studies, and observational studies on the effects of iodine supplementation in mildly-to-moderately iodine deficiency pregnant women on maternal and infant thyroid function and child neurodevelopmental outcomes.

    Article  PubMed  Google Scholar 

  131. World Health Organization. Iodine supplementation in pregnant and lactating women. WHO http://www.who.int/elena/titles/iodine_pregnancy/en/ (2021).

  132. De Groot, L. et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 97, 2543–2565 (2012).

    Article  PubMed  Google Scholar 

  133. Obican, S. G., Jahnke, G. D., Soldin, O. P. & Scialli, A. R. Teratology public affairs committee position paper: iodine deficiency in pregnancy. Birth Defects Res. A Clin. Mol. Teratol. 94, 677–682 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Leung, A. M., Pearce, E. N., Braverman, L. E. & Stagnaro-Green, A. AAP recommendations on iodine nutrition during pregnancy and lactation. Pediatrics 134, e1282 (2014).

    Article  PubMed  Google Scholar 

  135. Kung, A. W. C., Chau, M. T., Lao, T. T., Tam, S. C. F. & Low, L. C. K. The effect of pregnancy on thyroid nodule formation. J. Clin. Endocrinol. Metab. 87, 1010–1014 (2002).

    Article  CAS  PubMed  Google Scholar 

  136. Gao, M. et al. Excessive iodine intake is associated with formation of thyroid nodules in pregnant Chinese women. Nutr. Res. 66, 61–67 (2019).

    Article  CAS  PubMed  Google Scholar 

  137. Sahin, S. B. et al. Alterations of thyroid volume and nodular size during and after pregnancy in a severe iodine-deficient area. Clin. Endocrinol. 81, 762–768 (2014).

    Article  Google Scholar 

  138. Haugen, B. R. et al. 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, 1–133 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Smith, L. H., Danielsen, B., Allen, M. E. & Cress, R. Cancer associated with obstetric delivery: results of linkage with the California cancer registry. Am. J. Obstet. Gynecol. 189, 1128–1135 (2003).

    Article  PubMed  Google Scholar 

  140. Yasmeen, S. et al. Thyroid cancer in pregnancy. Int. J. Gynaecol. Obstet. 91, 15–20 (2005).

    Article  CAS  PubMed  Google Scholar 

  141. Pitt, S. C. et al. Patients’ reaction to diagnosis with thyroid cancer or an indeterminate thyroid nodule. Thyroid 31, 580–588 (2021).

    Article  CAS  PubMed  Google Scholar 

  142. Moosa, M. & Mazzaferri, E. L. Outcome of differentiated thyroid cancer diagnosed in pregnant women. J. Clin. Endocrinol. Metab. 82, 2862–2866 (1997).

    Article  CAS  PubMed  Google Scholar 

  143. Oh, H.-S. et al. Serial neck ultrasonographic evaluation of changes in papillary thyroid carcinoma during pregnancy. Thyroid 27, 773–777 (2017).

    Article  PubMed  Google Scholar 

  144. Ito, Y. et al. Effects of pregnancy on papillary microcarcinomas of the thyroid re-evaluated in the entire patient series at Kuma hospital. Thyroid 26, 156–160 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Vannucchi, G. et al. Clinical and molecular features of differentiated thyroid cancer diagnosed during pregnancy. Eur. J. Endocrinol. 162, 145–151 (2010).

    Article  CAS  PubMed  Google Scholar 

  146. Messuti, I. et al. Impact of pregnancy on prognosis of differentiated thyroid cancer: clinical and molecular features. Eur. J. Endocrinol. 170, 659–666 (2014).

    Article  CAS  PubMed  Google Scholar 

  147. Tazebay, U. H. et al. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat. Med. 6, 871–878 (2000).

    Article  CAS  PubMed  Google Scholar 

  148. Cho, G. J. et al. Risk of adverse obstetric outcomes and the abnormal growth of offspring in women with a history of thyroid cancer. Thyroid 29, 879–885 (2019).

    Article  CAS  PubMed  Google Scholar 

  149. Rakhlin, L., Fish, S. & Tuttle, R. M. Response to therapy status is an excellent predictor of pregnancy-associated structural disease progression in patients previously treated for differentiated thyroid. cancer. Thyroid 27, 396–401 (2017). This study assessed structural disease recurrence and progression during pregnancy in women with a history of papillary thyroid cancer.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Pearce, E. N. Management of thyrotoxicosis: preconception, pregnancy, and the postpartum period. Endocr. Pract. 25, 62–68 (2019).

    Article  PubMed  Google Scholar 

  151. Premawardhana, L. D. K. E., Parkes, A. B., John, R., Harris, B. & Lazarus, J. H. Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening. Thyroid 14, 610–615 (2004).

    Article  CAS  PubMed  Google Scholar 

  152. Amino, N. & Arata, N. Thyroid dysfunction following pregnancy and implications for breastfeeding. Best. Pract. Res. Clin. Endocrinol. Metab. 34, 101438 (2020).

    Article  CAS  PubMed  Google Scholar 

  153. Moleti, M. et al. Postpartum thyroiditis in women with euthyroid and hypothyroid hashimoto’s thyroiditis antedating pregnancy. J. Clin. Endocrinol. Metab. 105, e2421–e2428 (2020).

    Article  Google Scholar 

  154. Lucas, A. et al. Postpartum thyroiditis: long-term follow-up. Thyroid 15, 1177–1181 (2005).

    Article  PubMed  Google Scholar 

  155. Premawardhana, L. D. et al. Postpartum thyroiditis and long-term thyroid status: prognostic influence of thyroid peroxidase antibodies and ultrasound echogenicity. J. Clin. Endocrinol. Metab. 85, 71–75 (2000).

    Article  CAS  PubMed  Google Scholar 

  156. Ide, A. et al. Differentiation of postpartum Graves’ thyrotoxicosis from postpartum destructive thyrotoxicosis using antithyrotropin receptor antibodies and thyroid blood flow. Thyroid 24, 1027–1031 (2014).

    Article  CAS  PubMed  Google Scholar 

  157. Amino, N. et al. Serum ratio of triiodothyronine to thyroxine, and thyroxine-binding globulin and calcitonin concentrations in Graves’ disease and destruction-induced thyrotoxicosis. J. Clin. Endocrinol. Metab. 53, 113–116 (1981).

    Article  CAS  PubMed  Google Scholar 

  158. Hubalewska-Dydejczyk, A., Duntas, L. & Gilis-Januszewska, A. Pregnancy, thyroid, and the potential use of selenium. Hormones 19, 47–53 (2020).

    Article  PubMed  Google Scholar 

  159. UNICEF. Guidance on the monitoring of salt iodization programmes and determination of population iodine status. UNICEF https://www.ign.org/p142003099.html?from=0142002801 (2018).

Download references

Author information

Authors and Affiliations

  1. Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, MA, USA

    Sun Y. Lee & Elizabeth N. Pearce

Authors
  1. Sun Y. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth N. Pearce
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Elizabeth N. Pearce.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Endocrinology thanks W. Teng and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, S.Y., Pearce, E.N. Assessment and treatment of thyroid disorders in pregnancy and the postpartum period. Nat Rev Endocrinol 18, 158–171 (2022). https://doi.org/10.1038/s41574-021-00604-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-021-00604-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing