Skip to main content
SpringerLink
Log in

Thyroid diseases during pregnancy: A number of important issues

  • Review
  • Published:
Hormones Aims and scope Submit manuscript

Abstract

The most common thyroid diseases during pregnancy are hyper- and hypothyroidism and their variants including isolated hypothyroxinemia (hypo-T4), autoimmune thyroid disease (AITD) and different types of goiter. AITD represents the main cause of hypothyroidism during pregnancy ranging in prevalence between 5 and 20% with an average of 7.8%. The incidence of isolated hypo-T4 is about 150 times higher compared to congenital hypothyroidism. Prevalence of Graves’ disease (GD) ranges between 0.1% and 1% and the Transient Gestational Hyperthyroidism Syndrome between 1 and 3%. Thyroid stimulating hormone (TSH) is a sensitive marker of thyroid dysfunction during pregnancy. Normal values have been modified recently with a downward shift. Thus, the upper normal range is now considered to be 2.5 mUI/mL in the first trimester and 3.0 mUI/mL for the remainder of pregnancy. Most studies have shown that children born to women with hypothyroidism during gestation had significantly lower scores in neuropsychological tests related to intelligence, attention, language, reading ability, school performance and visual motor performance. However, some studies have not confirmed these findings. On the other hand, multiple retrospective studies have shown that the risks of maternal and fetal/neonatal complications are directly related to the duration and inadequate control of maternal thyrotoxicosis. The latter is associated with a risk of spontaneous abortion, congestive heart failure, thyrotoxic storm, preeclampsia, preterm delivery, low birth weight and stillbirth. Despite the lack of consensus among professional organizations, recent studies, which are based on sophisticated analyses, support universal screening in all pregnant women in the first trimester for thyroid diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Vanderpump M, 2014 Thyroid and iodine nutritional status: a UK perspective. Clin Med 14: Suppl 6: s7–s11.

    Article  Google Scholar 

  2. Zimmermann MB, 2009 Iodine deficiency. Endocr Rev 30: 376–408.

    Article  CAS  PubMed  Google Scholar 

  3. Glinoer D, 1997 Regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 18: 404–433.

    Article  CAS  PubMed  Google Scholar 

  4. Krassas GE, Poppe K, Glinoer D, 2010 Thyroid function and human reproductive health. Endocr Rev 31: 702–755.

    Article  CAS  PubMed  Google Scholar 

  5. Abalovich M, Amino N, Barbour LA, et al, 2007 Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 92: S1–S47.

    Article  CAS  PubMed  Google Scholar 

  6. Krassas GE, Perros P, Kaprara A, 2008 Thyroid autoimmunity, infertility and miscarriage. Expert Rev Endocrinol Metab 3: 127–136.

    Article  Google Scholar 

  7. Kaprara A, Krassas GE, 2008 Thyroid autoimmunity and miscarriage. Hormones (Athens) 7: 294–302.

    Article  Google Scholar 

  8. Glinoer D 2005 Thyroid disease during pregnancy. In: Braverman L, Utiger R, eds. Werner’s and Ingbar’s the thyroid: a fundamental and clinical text. 9th ed, Lippincott Williams & Wilkins, Philadelphia; pp; 1086–1108.

    Google Scholar 

  9. Glinoer D, 2007 The importance of iodine nutrition during pregnancy. Public Health Nutr 10: 1542–1546.

    Article  PubMed  Google Scholar 

  10. Tortosa F, 2011 Subclinical thyroid dysfunction in pregnancy. Endocrinologia y Nutrición 58: 255–257.

    Article  PubMed  Google Scholar 

  11. Glinoer D, Spencer CA, 2010 Serum TSH determinations in pregnancy: how, when and why? Nat Rev Endocrinol 6: 526–529.

    Article  CAS  PubMed  Google Scholar 

  12. Anckaert E, Poppe K, Van Uytfanghe K, Schiettecatte J, Foulon W, Thienpont LM, 2010 FT4 immunoassays may display a pattern during pregnancy similar to the equilibrium dialysis ID—LC/tandem MS candidate reference measurement procedure in spite of susceptibility towards binding protein alterations. Clinica Chimica Acta 411: 1348–1353.

    Article  CAS  Google Scholar 

  13. Kahric-Janicic N, Soldin SJ, Soldin OP, West T, Gu J, Jonklaas J, 2007 Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy. Thyroid 17: 303–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mandel SJ, Spencer CA, Hollowell JG, 2005 Are detection and treatment of thyroid insufficiency in pregnancy feasible? Thyroid 15: 44–53.

    Article  PubMed  Google Scholar 

  15. Midgley JE, Hoermann R, 2013 Measurement of total rather than free thyroxine in pregnancy: the diagnostic implications. Thyroid 23: 259–261.

    Article  CAS  PubMed  Google Scholar 

  16. Lee RH, Spencer CA, Mestman JH, et al, 2009 Free T4 immunoassays are flawed during pregnancy. Am J Obstet Gynecol 200: 260–266.

    PubMed  Google Scholar 

  17. Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A, 2010 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.

    Article  PubMed  Google Scholar 

  18. Glinoer D, de Nayer P, Bourdoux P, et al, 1990 Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab 71: 276–287.

    Article  CAS  PubMed  Google Scholar 

  19. Morreale de Escobar G, Obregón MJ, Escobar del Rey F, 2000 Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab 85: 3975–3987.

    CAS  PubMed  Google Scholar 

  20. Patil-Sisodia K, Mestman JH, 2010 Graves hyperthyroidism and pregnancy: a clinical update. Endocr Pract 16: 118–129.

    Article  PubMed  Google Scholar 

  21. Goodwin TM, Montoro M, Mestman JH, Pekary AE, Hershman JM, 1992 The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin Endocrinol Metab 75: 1333–1337.

    PubMed  CAS  Google Scholar 

  22. LeBeau SO, Mandel SJ, 2006 Thyroid disorders during pregnancy. Endocrinol Metab Clin North Am 35: 117–136, vii.

    Article  PubMed  Google Scholar 

  23. Mestman JH, 1997 Hyperthyroidism in pregnancy. Clin Obstet Gynecol 40: 45–64.

    Article  CAS  PubMed  Google Scholar 

  24. Mestman JH, 2004 Hyperthyroidism in pregnancy. Best Pract Res Clin Endocrinol Metab 18: 267–288.

    Article  CAS  PubMed  Google Scholar 

  25. Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG, 1989 Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol 160: 63–70.

    Article  CAS  PubMed  Google Scholar 

  26. Millar LK, Wing DA, Leung AS, Koonings PP, Montoro MN, Mestman JH, 1994 Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism. Obstet Gynecol 84: 946–949.

    CAS  PubMed  Google Scholar 

  27. Phoojaroenchanachai M, Sriussadaporn S, Peerapatdit T, et al, 2001 Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight. Clin Endocrinol (Oxf) 54: 365–370.

    Article  CAS  Google Scholar 

  28. Sheffield JS, Cunningham FG, 2004 Thyrotoxicosis and heart failure that complicate pregnancy. Am J Obstet Gynecol 190: 211–217.

    Article  PubMed  Google Scholar 

  29. Smith C, Thomsett M, Choong C, Rodda C, McIntyre HD, Cotterill AM, 2001 Congenital thyrotoxicosis in premature infants. Clin Endocrinol (Oxf) 54: 371–376.

    Article  CAS  Google Scholar 

  30. Haddow JE, Knight GJ, Palomaki GE, McClain MR, Pulkkinen AJ, 2004 The reference range and within-person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy. J Med Screen 11: 170–174.

    Article  CAS  PubMed  Google Scholar 

  31. Chan GW, Mandel SJ, 2007 Therapy insight: management of Graves’ disease during pregnancy. Nat Clin Pract Endocrinol Metab 3: 470–478.

    Article  CAS  PubMed  Google Scholar 

  32. Momotani N, Ito K, 1991 Treatment of pregnant patients with Basedow’s disease. Exp Clin Endocrinol 97: 268–274.

    Article  CAS  PubMed  Google Scholar 

  33. Mandel SJ, Cooper DS, 2001 The use of antithyroid drugs in pregnancy and lactation. J Clin Endocrinol Metab 86: 2354–2359.

    Article  CAS  PubMed  Google Scholar 

  34. Clementi M, Di Gianantonio E, Pelo E, Mammi I, Basile RT, Tenconi R, 1999 Methimazole embryopathy: delineation of the phenotype. Am J Med Genet 83: 43–46.

    Article  CAS  PubMed  Google Scholar 

  35. Bournaud C, Orgiazzi J, 2003 Antithyroid agents and embryopathies. Ann Endocrinol (Paris) 64: 366–369.

    CAS  Google Scholar 

  36. Wolf D, Foulds N, Daya H, 2006 Antenatal Carbimazole and choanal atresia: a new embryopathy. Arch Otolaryngol Head Neck Surg 132: 1009–1011.

    Article  PubMed  Google Scholar 

  37. Van Dijke CP, Heydendael RJ, De Kleine MJ, 1987 Methimazole, Carbimazole, and congenital skin defects. Ann Int Med 106: 60–61.

    Article  PubMed  Google Scholar 

  38. Di Gianantonio E, Schaefer C, Mastroiacovo PP, et al, 2001 Adverse effects of prenatal methimazole exposure. Teratology 64: 262–266.

    Article  PubMed  Google Scholar 

  39. Barbero P, Valdez R, Rodriguez H, et al, 2008 Choanal atresia associated with maternal hyperthyroidism treated with methimazole: a case-control study. Am J Med Genet A 146A: 2390–2395.

    Article  PubMed  Google Scholar 

  40. Rivkees SA, Mattison DR, 2009 Ending propylthiouracil-induced liver failure in children. N Engl J Med 360: 1574–1575.

    Article  CAS  PubMed  Google Scholar 

  41. Rivkees SA, Mattison DR, 2009 Propylthiouracil (PTU) hepatoxicity in children and recommendations for discontinuation of use. Int J Pediatr Endocrinol 2009: 132041.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Karras S, Tzotzas T, Krassas GE, 2009 Antithyroid drugs used in the treatment of hyperthyroidism during breast feeding. An update and new perspectives. Hormones 8: 254–257.

    Article  PubMed  Google Scholar 

  43. Rivkees SA, Szarfman A, 2010 Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children. J Clin Endocrinol Metab 95: 3260–3267.

    Article  CAS  PubMed  Google Scholar 

  44. Rivkees SA, Mattison DR, Cooper DS, 2009 AACE Patient Safety-Editorials Propylthiouracil (PTU) Hepatotoxicity and Graves’ Disease Therapy. http://www.aacepatientsafetyexchange.com/editorial/index.php?id=25.

  45. Bahn RS, Burch HS, Cooper DS, 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: 673–674.

    Article  CAS  PubMed  Google Scholar 

  46. FDA Statement (Medwatch Online) 2009 Information for healthcare professionals—propylthiouracil-induced liver failure. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetylnformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm162701.htm (accessed June 17, 2010)

  47. Bulmus N, Ustuner I, Seda Guvendag Guven E, Kir Sahin F, Senturk S, Baydur Sahin S, 2013 Thyroid diseases in pregnancy: The importance of anamnesis. Pak J Med Sci 29: 1187–1192.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Medici M, Korevaar TI, Schalekamp-Timmermans S, et al, 2014 Maternal early-pregnancy thyroid function is associated with subsequent hypertensive disorders of pregnancy: the generation R study. J Clin Endocrinol Metab 99: E2591–E2598.

    Article  CAS  PubMed  Google Scholar 

  49. Su PY, Huang K, Hao JH, et al, 2011 Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. J Clin Endocrinol Metab 96: 3234–3241.

    Article  CAS  PubMed  Google Scholar 

  50. Ashoor G, Maiz N, Rotas M, Kametas NA, Nicolaides KH, 2010 Maternal thyroid function at 11 to 13 weeks of gestation and subsequent development of preeclampsia. Prenat Diagn 30: 1032–1038.

    Article  PubMed  Google Scholar 

  51. Agarwal MM, Dhatt GS, Punnose J, Bishawi B, Zayed R, 2006 Thyroid function abnormalities and antithyroid antibody prevalence in pregnant women at high risk for gestational diabetes mellitus. Gynecol Endocrinol 22: 261–266.

    Article  CAS  PubMed  Google Scholar 

  52. Karakosta P, Alegakis D, Georgiou V, et al, 2012 Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab 97: 4464–4472.

    Article  CAS  PubMed  Google Scholar 

  53. Haddow JE, Palomaki GE, Allan WC, et al, 1999 Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. New England Journal of Medicine 341: 549–555.

    Article  CAS  PubMed  Google Scholar 

  54. Li Y, Shan Z, Teng W, et al, 2010 Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25–30 months. Clin Endocrinol 72: 825–829.

    Article  CAS  Google Scholar 

  55. Pop VJ, Kuijpens JL, van Baar AL, et al, 1999 Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol 50: 149–155.

    Article  CAS  Google Scholar 

  56. Henrichs J, Bongers-Schokking JJ, Schenk JJ, et al, 2010 Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metab 95: 4227–4234.

    Article  CAS  PubMed  Google Scholar 

  57. Kooistra L, Crawford S, van Baar AL, Brouwers EP, Pop VJ 2006 Neonatal effects of maternal hypothyroxinemia during early pregnancy. Pediatrics 117: 161–167.

    Article  PubMed  Google Scholar 

  58. Finken MJ, van Eijsden M, Loomans EM, Vrijkotte TG, Rotteveel J, 2013 Maternal hypothyroxinemia in early pregnancy predicts reduced performance in reaction time tests in 5- to 6-year-old offspring. J Clin Endocrinol Metab 98: 1417–1426.

    Article  CAS  PubMed  Google Scholar 

  59. Julvez J, Alvarez-Pedrerol M, Rebagliato M, et al, 2012 Thyroxine levels during pregnancy in healthy women and early child neurodevelopment. Epidemiology 24: 150–157.

    Article  Google Scholar 

  60. Craig WY, Allan WC, Kloza EM, et al, 2012 Midgestational maternal free thyroxine concentration and offspring neurocognitive development at age two years. J Clin Endocrinol Metab 97: E22–E28.

    Article  CAS  PubMed  Google Scholar 

  61. Morreale de Escobar G, Obregón MJ, Escobar del Rey F, 2000 Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab 85: 3975–3987.

    CAS  PubMed  Google Scholar 

  62. Berbel P, Mestre JL, Santamaria A, et al, 2009 Delayed neurobehavioral development in children born to pregnant women with mild hypothyroxinemia during the first month of gestation: the importance of early iodine supplementation. Thyroid 19: 511–519.

    Article  CAS  PubMed  Google Scholar 

  63. Mannisto T, Mendola P, Reddy U, Laughon SK, 2013 Neonatal outcomes and birth weight in pregnancies complicated by maternal thyroid disease. American J Epidemiol 178: 731–740.

    Article  Google Scholar 

  64. Lazarus JH, Bestwick JP, Channon S, et al, 2012 Antenatal thyroid screening and childhood cognitive function. N Engl J Med 366: 493–501.

    Article  CAS  PubMed  Google Scholar 

  65. Stagnaro-Green A, Abalovich M, Alexander E, et al, 2011 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21: 1081–125.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Baskin HJ, Cobin RH, Duick DS, et al, 2002 American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 8: 457–469.

    Article  PubMed  Google Scholar 

  67. ACOG news release 2007 Routine thyroid screening not recommended for pregnant women. www.acog.org/from_home/publications/press_releases/nr10-01-07-1.cfm

  68. Vaidya B, Anthony S, Bilous M, et al, 2007 Detection of thyroid dysfunction in early pregnancy: universal screening or targeted high-risk case finding? J Clin Endocrinol Metab 92: 203–207.

    Article  CAS  PubMed  Google Scholar 

  69. Dosiou C, Sanders GD, Araki SS, Crapo LM, 2008 Screening pregnant women for autoimmune thyroid disease: a cost-effectiveness analysis. Eur J Endocrinol 158: 841–851.

    Article  CAS  PubMed  Google Scholar 

  70. Dosiou C, Barnes J, Schwartz A, Negro R, Crapo L, Stagnaro-Green A, 2012 Cost-effectiveness of universal and risk-based screening for autoimmune thyroid disease in pregnant women. J Clin Endocrinol Metab 97: 1536–1546.

    Article  CAS  PubMed  Google Scholar 

  71. Haddow JE, McClain MR, Palomaki GE, Kloza EM, Williams J, 2006 Screening for thyroid disorders during pregnancy: results of a survey in Maine. Am J Obstet Gynecol 194: 471–474.

    Article  PubMed  Google Scholar 

  72. Stricker R, Echenard M, Eberhart R, et al, 2007 Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age-specific reference intervals. Eur J Endocrinol 157: 509–514.

    Article  CAS  PubMed  Google Scholar 

  73. Panesar NS, Li CY, Rogers MS, 2001 Reference intervals for thyroid hormones in pregnant Chinese women. Ann Clin Biochem 38: 329–332.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cultural and Educational Center “G. & H. Krassas”, St. Paul Hospital, Thessaloniki, Greece

    Gerasimos Krassas MD, PhD, FRCP (Lond)

  2. Department of Endocrinology, St. Paul Hospital, Thessaloniki, Greece

    Spyridon N. Karras & Nikolaos Pontikides

Authors
  1. Gerasimos Krassas MD, PhD, FRCP (Lond)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Spyridon N. Karras
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikolaos Pontikides
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerasimos Krassas MD, PhD, FRCP (Lond).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krassas, G., Karras, S.N. & Pontikides, N. Thyroid diseases during pregnancy: A number of important issues. Hormones 14, 59–69 (2015). https://doi.org/10.1007/BF03401381

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03401381

Key words

Search

Navigation