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:

Antithyroid drug-induced fetal goitrous hypothyroidism

Nature Reviews Endocrinology volume 7, pages 396–406 (2011)Cite this article

Subjects

Abstract

Maternal overtreatment with antithyroid drugs can induce fetal goitrous hypothyroidism. This condition can have a critical effect on pregnancy outcome, as well as on fetal growth and neurological development. The purpose of this Review is to clarify if and how fetal goitrous hypothyroidism can be prevented, and how to react when prevention has failed. Understanding the importance of pregnancy-related changes in maternal thyroid status when treating a pregnant woman is crucial to preventing fetal goitrous hypothyroidism. Maternal levels of free T4 are the most consistent indication of maternal and fetal thyroid status. In patients with fetal goitrous hypothyroidism, intra-amniotic levothyroxine injections improve fetal outcome. The best way to avoid maternal overtreatment with antithyroid drugs is to monitor closely the maternal thyroid status, especially estimates of free T4 levels.

Key Points

  • Treating pregnant women with antithyroid drugs (ATDs) puts the fetus at risk of overtreatment and thus subsequent development of fetal hypothyroidism and goiter formation

  • Fetal goitrous hypothyroidism can cause severe pregnancy-related complications and potentially harm fetal growth and neurological development

  • Treatment of fetal goitrous hypothyroidism with intra-amniotic levothyroxine achieves better results than simply discontinuing maternal ATD treatment

  • Awareness of the pregnancy-related changes to maternal thyroid status is essential when treating maternal hyperthyroidism

  • Close monitoring of the maternal thyroid status, especially estimates of free T4 levels, is the best way to avoid overtreatment

  • Centralized care of pregnant women with Graves disease in specialized multidisciplinary units is urgently needed to maintain optimal fetal development

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

Figure 1: Pathways of fetal goiter development in connection to maternal antithyroid drug treatment for Graves disease.

Similar content being viewed by others

References

  1. Zoeller, R. T. & Rovet, J. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J. Neuroendocrinol. 16, 809–818 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. 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 

  3. Berbel, P. et al. 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 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Pop, V. J. et al. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: A 3-year follow-up study. Clin. Endocrinol. 59, 282–288 (2003).

    Article  Google Scholar 

  5. Friedland, D. R. & Rothschild, M. A. Rapid resolution of fetal goiter associated with maternal Grave's disease: a case report. Int. J. Pediatr. Otorhinolaryngol. 54, 59–62 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Glinoer, D. What happens to the normal thyroid during pregnancy? Thyroid 9, 631–635 (1999).

    Article  CAS  PubMed  Google Scholar 

  7. Tanaka, S. et al. Gestational transient hyperthyroxinaemia (GTH): Screening for thyroid function in 23,163 pregnant women using dried blood spots. Clin. Endocrinol. 49, 325–329 (1998).

    Article  CAS  Google Scholar 

  8. Dashe, J. S. et al. Thyroid-stimulating hormone in singleton and twin pregnancy: Importance of gestational age-specific reference ranges. Obstet. Gynecol. 106, 753–757 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Boas, M. et al. Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women. Eur. J. Endocrinol. 161, 903–910 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Haddow, J. E., Knight, G. J., Palomaki, G. E., McClain, M. R. & Pulkkinen, A. J. 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 (2004).

    Article  CAS  PubMed  Google Scholar 

  12. 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 

  13. Chan, S. Y., Vasilopoulou, E. & Kilby, M. D. The role of the placenta in thyroid hormone delivery to the fetus. Nat. Clin. Pract. Endocrinol. Metab. 5, 45–54 (2009).

    Article  CAS  PubMed  Google Scholar 

  14. Raymond, J. & LaFranchi, S. H. Fetal and neonatal thyroid function: review and summary of significant new findings. Curr. Opin. Endocrinol. Diabetes Obes. 17, 1–7 (2010).

    Article  PubMed  Google Scholar 

  15. Bernal, J. Thyroid hormone receptors in brain development and function. Nat. Clin. Pract. Endocrinol. Metab. 3, 249–259 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. 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  CAS  PubMed  Google Scholar 

  17. Kilby, M. D., Barber, K., Hobbs, E. & Franklyn, J. A. Thyroid hormone action in the placenta. Placenta 26, 105–113 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Koopdonk-Kool, J. M. et al. Type II and type III deiodinase activity in human placenta as a function of gestational age. J. Clin. Endocrinol. Metab. 81, 2154–2158 (1996).

    CAS  PubMed  Google Scholar 

  19. McKenzie, J. M. & Zakarija, M. Fetal and neonatal hyperthyroidism and hypothyroidism due to maternal TSH receptor antibodies. Thyroid 2, 155–159 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Weetman, A. P. The immunology of pregnancy. Thyroid 9, 643–646 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Polak, M. et al. Fetal cord blood sampling in the diagnosis and the treatment of fetal hyperthyroidism in the offsprings of a euthyroid mother, producing thyroid stimulating immunoglobulins. Ann. Endocrinol. (Paris) 58, 338–342 (1997).

    CAS  Google Scholar 

  22. Eguchi, Y., Fukiishi, Y. & Hasegawa, Y. Ontogeny of the pituitary-thyroid system in fetal rats: observations on the fetal thyroid after maternal treatment with goitrogen. Anat. Rec. 198, 637–642 (1980).

    Article  CAS  PubMed  Google Scholar 

  23. Eaton, J. C. Treatment of thyrotoxicosis with thiouracil. Lancet 245, 171–174 (1945).

    Article  Google Scholar 

  24. Weiner, S., Scharf, J. I., Bolognese, R. J. & Librizzi, R. J. Antenatal diagnosis and treatment of a fetal goiter. J. Reprod. Med. 24, 39–42 (1980).

    CAS  PubMed  Google Scholar 

  25. Davidson, K. M., Richards, D. S., Schatz, D. A. & Fisher, D. A. Successful in utero treatment of fetal goiter and hypothyroidism. N. Engl. J. Med. 324, 543–546 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Hadi, H. A. & Strickland, D. In utero treatment of fetal goitrous hypothyroidism caused by maternal Graves' disease. Am. J. Perinatol. 12, 455–458 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. Van Loon, A. J., Derksen, J. T., Bos, A. F. & Rouwé, C. W. In utero diagnosis and treatment of fetal goitrous hypothyroidism, caused by maternal use of propylthiouracil. Prenat. Diagn. 15, 599–604 (1995).

    Article  CAS  PubMed  Google Scholar 

  28. Nicolini, U., Venegoni, E., Acaia, B., Cortelazzi, D. & Beck-Peccoz, P. Prenatal treatment of fetal hypothyroidism: is there more than one option? Prenat. Diagn. 16, 443–448 (1996).

    Article  CAS  PubMed  Google Scholar 

  29. Bruner, J. P. & Dellinger, E. H. Antenatal diagnosis and treatment of fetal hypothyroidism. A report of two cases. Fetal Diagn. Ther. 12, 200–204 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Col, J. Y. Fetal goiter with hypothyroidism. A case report [French]. J. Gynecol. Obstet. Biol. Reprod. (Paris) 27, 193–196 (1998).

    CAS  Google Scholar 

  31. Maragliano, G. et al. Efficacy of oral iodide therapy on neonatal hyperthyroidism caused by maternal Graves' disease. Fetal Diagn. Ther. 15, 122–126 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Yanai, N. & Shveiky, D. Fetal hydrops, associated with maternal propylthiouracil exposure, reversed by intrauterine therapy. Ultrasound Obstet. Gynecol. 23, 198–201 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Nath, C. A. et al. Three-dimensional sonography in the evaluation and management of fetal goiter. Ultrasound Obstet. Gynecol. 25, 312–314 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Duclos, B., Ville, Y., Lenclen, R. & Paupe, A. Correct procedure in the presence of a fetal goiter associated with hypothyroidism. Observations from three cases [French]. Gynecol. Obstet. Fertil. 34, 34–37 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Lassen, P. D., Sundberg, K., Juul, A. & Skibsted, L. Fetal goiter and bilateral ovarian cysts. A case report. Fetal Diagn. Ther. 23, 124–127 (2007).

    Google Scholar 

  36. Miyata, I. et al. Successful intrauterine therapy for fetal goitrous hypothyroidism during late gestation. Endocr. J. 54, 813–817 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Koyuncu, F. M., Tamay, A. G. & Bugday, S. Intrauterine diagnosis and management of fetal goiter: A case report. J. Clin. Ultrasound 38, 503–505 (2010).

    Article  PubMed  Google Scholar 

  38. Bliddal, S. et al. Graves' disease in two pregnancies complicated by fetal goitrous hypothyroidism—successful in utero treatment with levothyroxine. Thyroid 21, 75–81 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. Belfar, H. L., Foley, T. P. Jr, Hill, L. M. & Kislak, S. Sonographic findings in maternal hyperthyroidism. Fetal hyperthyroidism/fetal goiter. J. Ultrasound Med. 10, 281–284 (1991).

    Article  CAS  PubMed  Google Scholar 

  40. Soliman, S., McGrath, F., Brennan, B. & Glazebrook, K. Color Doppler imaging of the thyroid gland in a fetus with congenital goiter: a case report. Am. J. Perinatol. 11, 21–23 (1994).

    Article  CAS  PubMed  Google Scholar 

  41. Ochoa-Maya, M. R., Frates, M. C., Lee-Parritz, A. & Seely, E. W. Resolution of fetal goiter after discontinuation of propylthiouracil in a pregnant woman with Graves' hyperthyroidism. Thyroid 9, 1111–1114 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Bellini, P. et al. Treatment of maternal hyperthyroidism and fetal goiter [Italian]. Minerva Ginecol. 52, 25–27 (2000).

    CAS  PubMed  Google Scholar 

  43. Lembet, A., Eroglu, D., Kinik, S. T., Gurakan, B. & Kuscu, E. Non-invasive management of fetal goiter during maternal treatment of hyperthyroidism in Grave's disease. Fetal Diagn. Ther. 20, 254–257 (2005).

    Article  PubMed  Google Scholar 

  44. Volumenie, J. L. et al. Management of fetal thyroid goitres: a report of 11 cases in a single perinatal unit. Prenat. Diagn. 20, 799–806 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Nachum, Z., Rakover, Y., Weiner, E. & Shalev, E. Graves' disease in pregnancy: prospective evaluation of a selective invasive treatment protocol. Am. J. Obstet. Gynecol. 189, 159–165 (2003).

    Article  PubMed  Google Scholar 

  46. Luton, D. et al. Management of Graves' disease during pregnancy: the key role of fetal thyroid gland monitoring. J. Clin. Endocrinol. Metab. 90, 6093–6098 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Bromley, B., Frigoletto, F. D. Jr, Cramer, D., Osathanondh, R. & Benacerraf, B. R. The fetal thyroid: normal and abnormal sonographic measurements. J. Ultrasound Med. 11, 25–28 (1992).

    Article  CAS  PubMed  Google Scholar 

  48. Dufour, P. et al. Graves' disease and pregnancy (29 cases and review of the literature) [French]. Revue Francaise de Gynecologie et d'Obstetrique. 92, 17–25 (1997).

    Google Scholar 

  49. Cohen, O. et al. Serial in utero ultrasonographic measurements of the fetal thyroid: a new complementary tool in the management of maternal hyperthyroidism in pregnancy. Prenat. Diagn. 23, 740–742 (2003).

    Article  PubMed  Google Scholar 

  50. Rosenfeld, H., Ornoy, A., Shechtman, S. & Diav-Citrin, O. Pregnancy outcome, thyroid dysfunction and fetal goitre after in utero exposure to propylthiouracil: a controlled cohort study. Br. J. Clin. Pharmacol. 68, 609–617 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Abalovich, M. et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 92 (Suppl.), S1–S47 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Grüner, C. et al. Intrauterine treatment of fetal goitrous hypothyroidism controlled by determination of thyroid-stimulating hormone in fetal serum. A case report and review of the literature. Fetal Diagn. Ther. 16, 47–51 (2001).

    Article  PubMed  Google Scholar 

  53. Marsál, K. et al. Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr. 85, 843–848 (1996).

    Article  PubMed  Google Scholar 

  54. Olsen, I. E., Groveman, S. A., Lawson, M. L., Clark, R. H. & Zemel, B. S. New intrauterine growth curves based on United States data. Pediatrics 125, e214–e224 (2010).

    Article  PubMed  Google Scholar 

  55. Stagnaro-Green, A. Maternal thyroid disease and preterm delivery. J. Clin. Endocrinol. Metab. 94, 21–25 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. Pop, V. J. et al. Low concentrations of maternal thyroxin during early gestation: A risk factor of breech presentation? BJOG 111, 925–930 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Kuppens, S. M. et al. Maternal thyroid function during gestation is related to breech presentation at term. Clin. Endocrinol. (Oxf.) 72, 820–824 (2010).

    Article  CAS  Google Scholar 

  58. 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  CAS  PubMed  Google Scholar 

  59. LaFranchi, S. H., Haddow, J. E. & Hollowell, J. G. Is thyroid inadequacy during gestation a risk factor for adverse pregnancy and developmental outcomes? Thyroid 15, 60–71 (2005).

    Article  PubMed  Google Scholar 

  60. Dallas, J. S. Autoimmune thyroid disease and pregnancy: relevance for the child. Autoimmunity 36, 339–350 (2003).

    Article  PubMed  Google Scholar 

  61. Glinoer, D. Management of hypo- and hyperthyroidism during pregnancy. Growth Horm. IGF Res. 13 (Suppl. 1), S45–S54 (2003).

    Article  CAS  PubMed  Google Scholar 

  62. Glinoer, D. Thyroid hyperfunction during pregnancy. Thyroid 8, 859–864 (1998).

    Article  CAS  PubMed  Google Scholar 

  63. Mitsuda, N. et al. Risk factors for developmental disorders in infants born to women with Graves disease. Obstet. Gynecol. 80, 359–364 (1992).

    CAS  PubMed  Google Scholar 

  64. 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 

  65. Mestman, J. H., Manning, P. R. & Hodgman, J. Hyperthyroidism and pregnancy. Arch. Intern. Med. 134, 434–439 (1974).

    Article  CAS  PubMed  Google Scholar 

  66. Marchant, B., Brownlie, B. E., Hart, D. M., Horton, P. W. & Alexander, W. D. The placental transfer of propylthiouracil, methimazole and carbimazole. J. Clin. Endocrinol. Metab. 45, 1187–1193 (1977).

    Article  CAS  PubMed  Google Scholar 

  67. Mortimer, R. H. et al. Methimazole and propylthiouracil equally cross the perfused human term placental lobule. J. Clin. Endocrinol. Metab. 82, 3099–3102 (1997).

    CAS  PubMed  Google Scholar 

  68. 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 

  69. Wing, D. A., Millar, L. K., Koonings, P. P., Montoro, M. N. & Mestman, J. H. A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy. Am. J. Obstet. Gynecol. 170, 90–95 (1994).

    Article  CAS  PubMed  Google Scholar 

  70. Clementi, M. et al. Methimazole embryopathy: delineation of the phenotype. Am. J. Med. Genet. 83, 43–46 (1999).

    Article  CAS  PubMed  Google Scholar 

  71. Milham, S. Jr. Scalp defects in infants of mothers treated for hyperthyroidism with methimazole or carbimazole during pregnancy. Teratology 32, 321 (1985).

    Article  PubMed  Google Scholar 

  72. Di Gianantonio, E. et al. Adverse effects of prenatal methimazole exposure. Teratology 64, 262–266 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Martínez-Frías, M. L., Cereijo, A., Rodríguez-Pinilla, E. & Urioste, M. Methimazole in animal feed and congenital aplasia cutis. Lancet 339, 742–743 (1992).

    Article  PubMed  Google Scholar 

  74. Barbero, P. et al. Choanal atresia associated with maternal hyperthyroidism treated with methimazole: a case–control study. Am. J. Med. Genet. A 146A, 2390–2395 (2008).

    Article  PubMed  Google Scholar 

  75. Cheron, R. G., Kaplan, M. M., Larsen, P. R., Selenkow, H. A. & Crigler, J. F. Jr. Neonatal thyroid function after propylthiouracil therapy for maternal Graves' disease. N. Engl. J. Med. 304, 525–528 (1981).

    Article  CAS  PubMed  Google Scholar 

  76. Clementi, M. et al. Treatment of hyperthyroidism in pregnancy and birth defects. J. Clin. Endocrinol. Metab. 95, E337–E341 (2010).

    Article  PubMed  Google Scholar 

  77. US Department of Health and Human Safety FDA safety information for propylthiouracil [online], (2010).

  78. Williams, K. V., Nayak, S., Becker, D., Reyes, J. & Burmeister, L. A. Fifty years of experience with propylthiouracil-associated hepatotoxicity: what have we learned? J. Clin. Endocrinol. Metab. 82, 1727–1733 (1997).

    CAS  PubMed  Google Scholar 

  79. Bahn, R. S. et al. 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 (2009).

    Article  CAS  PubMed  Google Scholar 

  80. Russo, M. W., Galanko, J. A., Shrestha, R., Fried, M. W. & Watkins, P. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl. 10, 1018–1023 (2004).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  82. Hayashida, C. Y., Duarte, A. J., Sato, A. E. & Yamashiro-Kanashiro, E. H. Neonatal hepatitis and lymphocyte sensitization by placental transfer of propylthiouracil. J. Endocrinol. Invest. 13, 937–941 (1990).

    Article  CAS  PubMed  Google Scholar 

  83. Baker, B. et al. Unusual complications of antithyroid drug therapy: four case reports and review of literature. Thyroidology 1, 17–26 (1989).

    CAS  PubMed  Google Scholar 

  84. Kang, H. et al. A case of methimazole-induced acute hepatic failure in a patient with chronic hepatitis B carrier. Korean J. Intern. Med. 5, 69–73 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. US Department of Health and Human Safety Information for healthcare professionals—propylthiouracil-induced liver failure [online], (2010).

  86. Momotani, N. & Ito, K. Treatment of pregnant patients with Basedow's disease. Exp. Clin. Endocrinol. 97, 268–274 (1991).

    Article  CAS  PubMed  Google Scholar 

  87. Weetman, A. P. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat. Rev. Endocrinol. 6, 311–318 (2010).

    Article  CAS  PubMed  Google Scholar 

  88. Smyth, P. P. et al. Sequential studies on thyroid antibodies during pregnancy. Thyroid 15, 474–477 (2005).

    Article  CAS  PubMed  Google Scholar 

  89. Momotani, N., Noh, J., Oyanagi, H., Ishikawa, N. & Ito, K. Antithyroid drug therapy for Graves' disease during pregnancy. Optimal regimen for fetal thyroid status. N. Engl. J. Med. 315, 24–28 (1986).

    Article  CAS  PubMed  Google Scholar 

  90. Baloch, Z. et al. in NACB: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease (eds Demers, L. M. & Spencer, C. A) 1–125 (National Academy of Clinical Biochemistry, Washington, DC, 2002).

    Google Scholar 

  91. Feldt-Rasmussen, U. in The Thyroid and Reproduction. Merck European Thyroid Symposium Riga 2008 (eds Lazarus, J., Pirags, V. & Butz, S.) 77–83 (Georg Thieme Verlag, Stuttgart, 2008).

    Google Scholar 

  92. Wang, R., Nelson, J. C., Weiss, R. M. & Wilcox, R. B. Accuracy of free thyroxine measurements across natural ranges of thyroxine binding to serum proteins. Thyroid 10, 31–39 (2000).

    Article  CAS  PubMed  Google Scholar 

  93. Kahric-Janicic, N. et al. Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy. Thyroid 17, 303–311 (2007).

    Article  CAS  PubMed  Google Scholar 

  94. Vaidya, B. et al. Detection of thyroid dysfunction in early pregnancy: Universal screening or targeted high-risk case finding? J. Clin. Endocrinol. Metab. 92, 203–207 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Burrow, G. N. Neonatal goiter after maternal propylthiouracil therapy. J. Clin. Endocrinol. Metab. 25, 403–408 (1965).

    Article  CAS  PubMed  Google Scholar 

  96. Mujtaba, Q. & Burrow, G. N. Treatment of hyperthyroidism in pregnancy with propylthiouracil and methimazole. Obstet. Gynecol. 46, 282–286 (1975).

    CAS  PubMed  Google Scholar 

  97. Stice, R. C., Grant, C. S., Gharib, H. & van Heerden, J. A. The management of Graves' disease during pregnancy. Surg. Gynecol. Obstet. 158, 157–160 (1984).

    CAS  PubMed  Google Scholar 

  98. Rosenfeld, H., Ornoy, A., Shechtman, S. & Diav-Citrin, O. Pregnancy outcome, thyroid dysfunction and fetal goitre after in utero exposure to propylthiouracil: a controlled cohort study. Br. J. Clin. Pharmacol. 68, 609–617 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Cortelazzi, D. et al. Maternal compound W serial measurements for the management of fetal hypothyroidsm. Eur. J. Endocrinol. 141, 570–578 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. Vanmiddlesworth, L. et al. Thyroid function and 3,3′-diiodothyronine sulfate cross-reactive substance (compound w) in maternal hyperthyroidism with antithyroid treatment. Endocr. Pract. 16, 1–18 (2010).

    Google Scholar 

  101. Huel, C. et al. Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter. Ultrasound Obstet. Gynecol. 33, 412–420 (2009).

    Article  CAS  PubMed  Google Scholar 

  102. Seeds, J. W. Diagnostic mid trimester amniocentesis: how safe? Am. J. Obstet. Gynecol. 191, 607–615 (2004).

    Article  PubMed  Google Scholar 

  103. Polk, D. H. Diagnosis and management of altered fetal thyroid status. Clin. Perinatol. 21, 647–662 (1994).

    Article  CAS  PubMed  Google Scholar 

  104. Mujezinovic, F. & Alfirevic, Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstet. Gynecol. 110, 687–694 (2007).

    Article  PubMed  Google Scholar 

  105. Daffos, F. Fetal blood sampling. Annu. Rev. Med. 40, 319–329 (1989).

    Article  CAS  PubMed  Google Scholar 

  106. Ranzini, A. C. et al. Ultrasonography of the fetal thyroid: nomograms based on biparietal diameter and gestational age. J. Ultrasound Med. 20, 613–617 (2001).

    Article  CAS  PubMed  Google Scholar 

  107. Thorpe-Beeston, J. G., Nicolaides, K. H., Felton, C. V., Butler, J. & McGregor, A. M. Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus. N. Engl. J. Med. 324, 532–536 (1991).

    Article  CAS  PubMed  Google Scholar 

  108. Lightner, E. S., Fismer, F. A., Giles, H. & Woolfenden, J. Intra-amniotic injection of thyroxine (T4Y to a human fetus. Evidence for conversion of T4 to reverse T3. Am. J. Obstet. Gynecol. 127, 487–490 (1977).

    Article  CAS  PubMed  Google Scholar 

  109. Klein, A. H., Hobel, C. J., Sack, J. & Fisher, D. A. Effect of intraamniotic fluid thyroxine injection on fetal serum and amniotic fluid iodothyronine concentrations. J. Clin. Endocrinol. Metab. 47, 1034–1037 (1978).

    Article  CAS  PubMed  Google Scholar 

  110. Ribault, V. et al. Experience with intraamniotic thyroxine treatment in nonimmune fetal goitrous hypothyroidism in 12 cases. J. Clin. Endocrinol. Metab. 94, 3731–3739 (2009).

    Article  CAS  PubMed  Google Scholar 

  111. Hashimoto, H., Hashimoto, K. & Suehara, N. Successful in utero treatment of fetal goitrous hypothyroidism: case report and review of the literature. Fetal Diagn. Ther. 21, 360–365 (2006).

    Article  CAS  PubMed  Google Scholar 

  112. Henrichs, J. et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J. Clin. Endocrinol. Metab. 95, 4227–4234 (2010).

    Article  CAS  PubMed  Google Scholar 

  113. Pop, V. J. et al. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin. Endocrinol. (Oxf.) 59, 282–288 (2003).

    Article  Google Scholar 

  114. Lavado-Autric, R. et al. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J. Clin. Invest. 111, 1073–1082 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Burrow, G. N., Bartsocas, C., Klatskin, E. H. & Grunt, J. A. Children exposed in utero to propylthiouracil. Subsequent intellectual and physical development. Am. J. Dis. Child. 116, 161–165 (1968).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

U. Feldt-Rasmussen has received a grant from Arvid Nilsson's Foundation. S. Bliddal is supported by a grant from the Danish Council for Independent Research: Medical Sciences and has received grants from the H. Plesner Foundation and the William and Hugo Evers Foundation. C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. Department of Medical Endocrinology, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Sofie Bliddal, Åse Krogh Rasmussen & Ulla Feldt-Rasmussen

  2. Department of Fetal Medicine and Ultrasound, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Karin Sundberg & Vibeke Brocks

Authors
  1. Sofie Bliddal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Åse Krogh Rasmussen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karin Sundberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vibeke Brocks
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ulla Feldt-Rasmussen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S. Bliddal researched the data and wrote the article. S. Bliddal, Å. Krogh Rasmussen and U. Feldt-Rasmussen contributed to discussion of the content. All authors reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Ulla Feldt-Rasmussen.

Ethics declarations

Competing interests

U. Feldt-Rasmussen has received honoraries for teaching at Merck Serono symposia. The other authors declare no competing interests.

Supplementary information

Supplementary information

Methods (DOC 235 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bliddal, S., Rasmussen, Å., Sundberg, K. et al. Antithyroid drug-induced fetal goitrous hypothyroidism. Nat Rev Endocrinol 7, 396–406 (2011). https://doi.org/10.1038/nrendo.2011.34

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2011.34

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