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Graves’ Disease and Pregnancy

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Graves' Disease

Abstract

Graves’ disease, an autoimmune disorder caused by an IgG immunoglobulin stimulating the TSH receptor (TSI – thyroid-stimulating immunoglobulin), is the most common form of thyrotoxicosis in pregnancy. During pregnancy, the immune system undergoes a selective immunosuppression resulting in a decline in TSI titer with a concomitant decrease in thyrotoxicosis severity. An immunologic rebound occurs postpartum accompanied by increased TSI titers and an aggravation of thyrotoxicosis. The prevalence of Graves’ disease in pregnancy is 0.5 %. There is an increased prevalence on new-onset Graves’ disease in the postpartum period. Diagnosis of Graves’ disease during pregnancy consists of an elevated thyroxine and/or triioodothyronine and a suppressed TSH in a woman who tests positive for TSI. High maternal titers of TSI at delivery can result in neonatal thyrotoxicosis. Gestational thyrotoxicosis is secondary to the thyrotrophic effect of human chorionic gonadotropin, is self-limiting, and does not require treatment. Management of Graves’ thyrotoxicosis is predominately via antithyroid drugs. Propylthiouracil is recommended in the first trimester and methimazole is preferred during the second and third trimesters. Surgery is indicated in the second trimester in rare circumstances and radioactive iodine is contraindicated during pregnancy. Women with Graves’ disease preconception should be rendered euthyroid prior to conception.

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References

  1. Parry CH. Collections from the unpublished medical writings of the late caleb hillier parry, vol. 2. London: Underwoods; 1825. p. 111.

    Google Scholar 

  2. Seitz L. Trans Deuts Ges f Gyn. 1913;i:213.

    Google Scholar 

  3. Hyman HT, Kessel L. Studies of exophthalmic goiter and the involuntary nervous system XIV. Relationship to sex life of the female. J Am Med Assoc. 1927;88(26):2032–4.

    Article  Google Scholar 

  4. Gardiner-Hill H. Pregnancy complicating simple goitre and Graves’s disease. Lancet. 1929;213(5499):120–4.

    Article  Google Scholar 

  5. Astwood EB. The use of antithyroid drugs during pregnancy. J Clin Endocrinol Metab. 1951;10:1045–56.

    Article  Google Scholar 

  6. Morshed SA, Latif R, Davies TF. Delineating the autoimmune mechanisms in Graves’ disease. Immunol Res. 2012;54(1–3):191–203. doi:10.1007/s12026-012-8312-8.

    Article  CAS  PubMed  Google Scholar 

  7. Galofe JC, Duntas LH, Premawardhana LD, Davies TF. Advances in Graves’ disease. J Thyroid Res. 2012. doi:10.1155/2012/809231.

  8. Ando T, Imaizumi M, Graves PN, Unger P, Davies TF. Intrathyroidal fetal microchimerism in Graves’ disease. J Clin Endocrinol Metab. 2002;87(7):3315–20.

    CAS  PubMed  Google Scholar 

  9. Stagnaro-Green A. Overt hyperthyroidism and hypothyroidism during pregnancy. Clin Obstet Gynecol. 2011;54(3):478–87.

    Article  PubMed  Google Scholar 

  10. Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG. Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol. 1989;160(1):63–70. 0002-9378(89)90088-4 [pii].

    Article  CAS  PubMed  Google Scholar 

  11. Sheffield JS, Cunningham FG. Thyrotoxicosis and heart failure that complicate pregnancy. Am J Obstet Gynecol. 2004;190(1):211–7. S000293780300944X [pii].

    Article  PubMed  Google Scholar 

  12. Korelitz JJ, McNally DL, Masters MN, Li SX, Xu Y, Rivkees SA. Prevalence of thyrotoxicosis, antithyroid medication use, and complications among pregnant women in the United States. Thyroid. 2013;23(6):758–65. doi:10.1089/thy.2012.0488.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Amino N, Tanizawa O, Mori H, et al. Aggravation of thyrotoxicosis in early pregnancy and after delivery in Graves’ disease. J Clin Endocrinol Metab. 1982;55(1):108–12. doi:10.1210/jcem-55-1-108.

    Article  CAS  PubMed  Google Scholar 

  14. Jansson R, Dahlberg PA, Winsa B, Meirik O, Safwenberg J, Karlsson A. The postpartum period constitutes an important risk for the development of clinical Graves’ disease in young women. Acta Endocrinol (Copenh). 1987;116(3):321–5.

    CAS  Google Scholar 

  15. Tada H, Hidaka Y, Tsuruta E, et al. Prevalence of postpartum onset of disease within patients with Graves’ disease of child-bearing age. Endocr J. 1994;41(3):325–7.

    Article  CAS  PubMed  Google Scholar 

  16. Rochester DB, Davies T. Increased risk of Graves’ disease after pregnancy. Thyroid. 2005;15(11):1287–90.

    Article  Google Scholar 

  17. Rotondi M, Pirali B, Lodigiani S, et al. The post partum period and the onset of Graves’ disease: an overestimated risk factor. Eur J Endocrinol. 2008;159(2):161–5. doi:10.1530/EJE-08-0236.

    Article  CAS  PubMed  Google Scholar 

  18. Easterling TR, Schmucker BC, Carlson KL, Millard SP, Benedetti TJ. Maternal hemodynamics in pregnancies complicated by hyperthyroidism. Obstet Gynecol. 1991;78(3 Pt 1):348–52.

    CAS  PubMed  Google Scholar 

  19. Goodwin TM, Hershman JM. Hyperthyroidism due to inappropriate production of human chorionic gonadotropin. Clin Obstet Gynecol. 1997;40(1):32–44.

    Article  CAS  PubMed  Google Scholar 

  20. Glinoer D. Thyroid hyperfunction during pregnancy. Thyroid. 1998;8(9):859–64.

    Article  CAS  PubMed  Google Scholar 

  21. Yeo CP, Khoo DH, Eng PH, Tan HK, Yo SL, Jacob E. 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 (Oxf). 2001;55(3):391–8. 1353 [pii].

    Article  CAS  Google Scholar 

  22. Grun JP, Meuris S, De Nayer P, Glinoer D. The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies. Clin Endocrinol (Oxf). 1997;46(6):719–25.

    Article  CAS  Google Scholar 

  23. Lockwood CM, Grenache DG, Gronowski AM. Serum human chorionic gonadotropin concentrations greater than 400,000 IU/L are invariably associated with suppressed serum thyrotropin concentrations. Thyroid. 2009;19(8):863–8. doi:10.1089/thy.2009.0079.

    Article  CAS  PubMed  Google Scholar 

  24. Sun S, Qiu X, Zhou J. Clinical analysis of 65 cases of hyperemesis gravidarum with gestational transient thyrotoxicosis. J Obstet Gynaecol Res. 2014;40(6):1567–72. doi:10.1111/jog.12372.

    Article  CAS  PubMed  Google Scholar 

  25. Brown RS. Autoimmune thyroid disease in pregnant women and their offspring. Endocr Pract. 1996;2(1):53–61. NDA22V3727RCJ3VX.

    Article  CAS  PubMed  Google Scholar 

  26. Clavel S, Madec AM, Bornet H, Deviller P, Stefanutti A, Orgiazzi J. Anti TSH-receptor antibodies in pregnant patients with autoimmune thyroid disorder. Br J Obstet Gynaecol. 1990;97(11):1003–8.

    Article  CAS  PubMed  Google Scholar 

  27. Zimmerman D. Fetal and neonatal hyperthyroidism. Thyroid. 1999;9(7):727–33.

    Article  CAS  PubMed  Google Scholar 

  28. Chopra IJ. Commentary: fetal and neonatal hyperthyroidism. Thyroid. 1992;2(2):161–3.

    Article  CAS  PubMed  Google Scholar 

  29. Polak M. Hyperthyroidism in early infancy: pathogenesis, clinical features and diagnosis with a focus on neonatal hyperthyroidism. Thyroid. 1998;8(12):1171–7.

    Article  CAS  PubMed  Google Scholar 

  30. Matsuura N, Konishi J, Fujieda K, et al. TSH-receptor antibodies in mothers with Graves’ disease and outcome in their offspring. Lancet. 1988;1(8575-6):14–7. S0140-6736(88)91001-X [pii].

    Article  CAS  PubMed  Google Scholar 

  31. Peleg D, Cada S, Peleg A, Ben-Ami M. The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis. Obstet Gynecol. 2002;99(6):1040–3. S0029784402019610.

    Article  PubMed  Google Scholar 

  32. Zakarija M, McKenzie JM. Pregnancy-associated changes in the thyroid-stimulating antibody of Graves’ disease and the relationship to neonatal hyperthyroidism. J Clin Endocrinol Metab. 1983;57(5):1036–40. doi:10.1210/jcem-57-5-1036.

    Article  CAS  PubMed  Google Scholar 

  33. Skuza KA, Sills IN, Stene M, Rapaport R. Prediction of neonatal hyperthyroidism in infants born to mothers with graves disease. J Pediatr. 1996;128(2):264–8. S0022-3476(96)70405-5 [pii].

    Article  CAS  PubMed  Google Scholar 

  34. Levy-Shraga Y, Tamir-Hostovsky L, Boyko V, Lerner-Geva L, Pinhas-Hamiel O. Follow-up of newborns of mothers with Graves’ disease. Thyroid. 2014;24(6):1032–9. doi:10.1089/thy.2013.0489.

    Article  CAS  PubMed  Google Scholar 

  35. Phoojaroenchanachai M, Sriussadaporn S, Peerapatdit T, et al. Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight. Clin Endocrinol (Oxf). 2001;54(3):365–70. cen1224 [pii].

    Article  CAS  Google Scholar 

  36. Mitsuda N, Tamaki H, Amino N, Hosono T, Miyai K, Tanizawa O. Risk factors for developmental disorders in infants born to women with Graves disease. Obstet Gynecol. 1992;80(3 Pt 1):359–64.

    CAS  PubMed  Google Scholar 

  37. Luewan S, Chakkabut P, Tongsong T. Outcomes of pregnancy complicated with hyperthyroidism: a cohort study. Arch Gynecol Obstet. 2011;283(2):243–7. doi:10.1007/s00404-010-1362-z.

    Article  PubMed  Google Scholar 

  38. Andersen SL, Olsen J, Wu CS, Laurberg P. Low birth weight in children born to mothers with hyperthyroidism and high birth weight in hypothyroidism, whereas preterm birth is common in both conditions: a Danish national hospital register study. Eur Thyroid J. 2013;2(2):135–44. doi:10.1159/000350513.

    PubMed Central  CAS  PubMed  Google Scholar 

  39. Sahu MT, Das V, Mittal S, Agarwal A, Sahu M. Overt and subclinical thyroid dysfunction among Indian pregnant women and its effect on maternal and fetal outcome. Arch Gynecol Obstet. 2010;281(2):215–20. doi:10.1007/s00404-009-1105-1.

    Article  PubMed  Google Scholar 

  40. Mannisto T, Mendola P, Grewal J, Xie Y, Chen Z, Laughon SK. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J Clin Endocrinol Metab. 2013;98(7):2725–33. doi:10.1210/jc.2012-4233.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Ishikawa N. The relationship between neonatal developmental dysplasia of the hip and maternal hyperthyroidism. J Pediatr Orthop. 2008;28(4):432–4. doi:10.1097/BPO.0b013e318168d167.

    Article  PubMed  Google Scholar 

  42. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081–125. doi:10.1089/thy.2011.0087.

    Article  PubMed Central  PubMed  Google Scholar 

  43. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543–65. doi:10.1210/jc.2011-2803.

    Article  PubMed  Google Scholar 

  44. Luton D, Le Gac I, Vuillard E, et al. Management of graves’ disease during pregnancy: The key role of fetal thyroid gland monitoring. J Clin Endocrinol Metab. 2005;90(11):6093–8. jc.2004-2555.

    Article  CAS  PubMed  Google Scholar 

  45. McNab T, Ginsberg J. Use of anti-thyroid drugs in euthyroid pregnant women with previous Graves’ disease. Clin Invest Med. 2005;28(3):127–31.

    PubMed  Google Scholar 

  46. Laurberg P, Bournaud C, Karmisholt J, Orgiazzi J. Management of Graves’ hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy. Eur J Endocrinol. 2009;160(1):1–8. doi:10.1530/EJE-08-0663.

    Article  CAS  PubMed  Google Scholar 

  47. Cooper DS, Rivkees SA. Putting propylthiouracil in perspective. J Clin Endocrinol Metab. 2009;94(6):1881–2. doi:10.1210/jc.2009-0850.

    Article  CAS  PubMed  Google Scholar 

  48. Yoshihara A, Noh J, Yamaguchi T, et al. Treatment of Graves’ disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. J Clin Endocrinol Metab. 2012;97(7):2396–403. doi:10.1210/jc.2011-2860.

    Article  CAS  PubMed  Google Scholar 

  49. Ochoa-Maya MR, Frates MC, Lee-Parritz A, Seely EW. Resolution of fetal goiter after discontinuation of propylthiouracil in a pregnant woman with Graves’ hyperthyroidism. Thyroid. 1999;9(11):1111–4.

    Article  CAS  PubMed  Google Scholar 

  50. Rotondi M, Cappelli C, Pirali B, et al. The effect of pregnancy on subsequent relapse from Graves’ disease after a successful course of antithyroid drug therapy. J Clin Endocrinol Metab. 2008;93(10):3985–8. doi:10.1210/jc.2008-0966.

    Article  CAS  PubMed  Google Scholar 

  51. Yoshihara A, Noh JY, Watanabe N, et al. Lower incidence of postpartum thyrotoxicosis in women with graves disease treated by radioiodine therapy than by subtotal thyroidectomy or with antithyroid drugs. Clin Nucl Med. 2014;39(4):326–9. doi:10.1097/RLU.0000000000000386.

    Article  PubMed  Google Scholar 

  52. Nagasaki T, et al. Thyroid blood flow as a useful predictor of relapse of Graves’ disease after normal delivery in patients with Graves’ disease. Biomed Pharmacother. 2010;64(2):113–7.

    Article  PubMed  Google Scholar 

  53. Lazarus JH. Pre-conception counselling in Graves’ disease. Eur Thyroid J. 2012;1(1):24–9. doi:10.1159/000336102.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Laurberg P, Wallin G, Tallstedt L, Abraham-Nordling M, Lundell G, Torring O. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol. 2008;158(1):69–75. doi:10.1530/EJE-07-0450.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Alex Stagnaro-Green M.D., M.H.P.E. .

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Stagnaro-Green, A. (2015). Graves’ Disease and Pregnancy. In: Bahn, R. (eds) Graves' Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2534-6_12

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  • DOI: https://doi.org/10.1007/978-1-4939-2534-6_12

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