Hyperthyroidism during pregnancy: Treatment
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
- Section Editors
- David S Cooper, MD
David S Cooper, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Thyroid Disease
- Professor of Medicine and International Health
- Johns Hopkins University School of Medicine
- Charles J Lockwood, MD, MHCM
Charles J Lockwood, MD, MHCM
- Section Editor — Obstetrics
- Senior Vice President, USF Health
- Dean, Morsani College of Medicine
- Professor, Obstetrics and Gynecology
- University of South Florida
The evaluation and treatment of pregnant women with hyperthyroidism parallels that of nonpregnant women and men, but presents some unique problems. There are several important issues that must be considered when hyperthyroidism occurs during pregnancy. These include understanding the indications for treatment, the therapeutic options for pregnant women, and the goals of antithyroid drug (ATD) therapy.
The treatment of hyperthyroidism during pregnancy is presented here. The clinical manifestations, diagnosis, and causes of hyperthyroidism and other aspects of thyroid disease during pregnancy are discussed separately. (See "Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes" and "Overview of thyroid disease in pregnancy".)
The Endocrine Society and the American Thyroid Association (ATA) have published clinical guidelines for the management of thyroid dysfunction during pregnancy that are similar to the approach outlined here [1-3]. Treatment recommendations are predominantly based upon observational studies and clinical experience.
Indications — Graves' disease and human chorionic gonadotropin (hCG)-mediated hyperthyroidism are the most common causes of hyperthyroidism during pregnancy; toxic adenomas and toxic multinodular goiter are seen less commonly. (See "Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes", section on 'Establishing the cause'.)
hCG-mediated hyperthyroidism (gestational transient thyrotoxicosis) is usually transient and does not require treatment. Similarly, the thyroid hyperfunction in women with hyperemesis gravidarum usually does not require treatment because it is mild and subsides as hCG production falls (typically by 14 to 18 weeks gestation). Women with severe hyperemesis, however, require treatment of dehydration with intravenous fluids. (See "Treatment and outcome of nausea and vomiting of pregnancy".)
- 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; 21:1081.
- Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 21:593.
- 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; 97:2543.
- Lydakis C, Lip GY, Beevers M, Beevers DG. Atenolol and fetal growth in pregnancies complicated by hypertension. Am J Hypertens 1999; 12:541.
- Lip GY, Beevers M, Churchill D, et al. Effect of atenolol on birth weight. Am J Cardiol 1997; 79:1436.
- Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. BMJ 1990; 301:587.
- Stoffer SS, Hamburger JI. Inadvertent 131I therapy for hyperthyroidism in the first trimester of pregnancy. J Nucl Med 1976; 17:146.
- Hyer S, Pratt B, Newbold K, Hamer C. Outcome of Pregnancy After Exposure to Radioiodine In Utero. Endocr Pract 2011; :1.
- Adali E, Yildizhan R, Kolusari A, et al. The use of plasmapheresis for rapid hormonal control in severe hyperthyroidism caused by a partial molar pregnancy. Arch Gynecol Obstet 2009; 279:569.
- Azezli A, Bayraktaroglu T, Topuz S, Kalayoglu-Besisik S. Hyperthyroidism in molar pregnancy: rapid preoperative preparation by plasmapheresis and complete improvement after evacuation. Transfus Apher Sci 2007; 36:87.
- American College of Obstetricians and Gynecologists.. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 37, August 2002. (Replaces Practice Bulletin Number 32, November 2001). Thyroid disease in pregnancy. Obstet Gynecol 2002; 100:387.
- Rubin PC. Current concepts: beta-blockers in pregnancy. N Engl J Med 1981; 305:1323.
- Sherif IH, Oyan WT, Bosairi S, Carrascal SM. Treatment of hyperthyroidism in pregnancy. Acta Obstet Gynecol Scand 1991; 70:461.
- Mortimer RH, Cannell GR, Addison RS, et al. Methimazole and propylthiouracil equally cross the perfused human term placental lobule. J Clin Endocrinol Metab 1997; 82:3099.
- Roti E, Minelli R, Salvi M. Clinical review 80: Management of hyperthyroidism and hypothyroidism in the pregnant woman. J Clin Endocrinol Metab 1996; 81:1679.
- Momotani N, Noh JY, Ishikawa N, Ito K. Effects of propylthiouracil and methimazole on fetal thyroid status in mothers with Graves' hyperthyroidism. J Clin Endocrinol Metab 1997; 82:3633.
- Momotani N, Noh J, Oyanagi H, et al. Antithyroid drug therapy for Graves' disease during pregnancy. Optimal regimen for fetal thyroid status. N Engl J Med 1986; 315:24.
- Burrow GN, Klatskin EH, Genel M. Intellectual development in children whose mothers received propylthiouracil during pregnancy. Yale J Biol Med 1978; 51:151.
- Eisenstein Z, Weiss M, Katz Y, Bank H. Intellectual capacity of subjects exposed to methimazole or propylthiouracil in utero. Eur J Pediatr 1992; 151:558.
- Van Dijke CP, Heydendael RJ, De Kleine MJ. Methimazole, carbimazole, and congenital skin defects. Ann Intern Med 1987; 106:60.
- Martínez-Frías ML, Cereijo A, Rodríguez-Pinilla E, Urioste M. Methimazole in animal feed and congenital aplasia cutis. Lancet 1992; 339:742.
- Bowman P, Osborne NJ, Sturley R, Vaidya B. Carbimazole embryopathy: implications for the choice of antithyroid drugs in pregnancy. QJM 2012; 105:189.
- Di Gianantonio E, Schaefer C, Mastroiacovo PP, et al. Adverse effects of prenatal methimazole exposure. Teratology 2001; 64:262.
- Johnsson E, Larsson G, Ljunggren M. Severe malformations in infant born to hyperthyroid woman on methimazole. Lancet 1997; 350:1520.
- Wilson LC, Kerr BA, Wilkinson R, et al. Choanal atresia and hypothelia following methimazole exposure in utero: a second report. Am J Med Genet 1998; 75:220.
- Foulds N, Walpole I, Elmslie F, Mansour S. Carbimazole embryopathy: an emerging phenotype. Am J Med Genet A 2005; 132A:130.
- Wing DA, Millar LK, Koonings PP, et al. A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy. Am J Obstet Gynecol 1994; 170:90.
- Clementi M, Di Gianantonio E, Pelo E, et al. Methimazole embryopathy: delineation of the phenotype. Am J Med Genet 1999; 83:43.
- 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 2009; 68:609.
- Bowman P, Vaidya B. Suspected Spontaneous Reports of Birth Defects in the UK Associated with the Use of Carbimazole and Propylthiouracil in Pregnancy. J Thyroid Res 2011; 2011:235130.
- 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; 97:2396.
- Andersen SL, Olsen J, Wu CS, Laurberg P. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J Clin Endocrinol Metab 2013; 98:4373.
- Chen CH, Xirasagar S, Lin CC, et al. Risk of adverse perinatal outcomes with antithyroid treatment during pregnancy: a nationwide population-based study. BJOG 2011; 118:1365.
- Andersen SL, Olsen J, Wu CS, Laurberg P. Severity of birth defects after propylthiouracil exposure in early pregnancy. Thyroid 2014; 24:1533.
- Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2007; 92:S1.
- Bahn RS, Burch HS, Cooper DS, 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 2009; 19:673.
- Cooper DS, Rivkees SA. Putting propylthiouracil in perspective. J Clin Endocrinol Metab 2009; 94:1881.
- Sheffield JS, Cunningham FG. Thyrotoxicosis and heart failure that complicate pregnancy. Am J Obstet Gynecol 2004; 190:211.
- Hamburger JI. Diagnosis and management of Graves' disease in pregnancy. Thyroid 1992; 2:219.
- Salvi M, How J. Pregnancy and autoimmune thyroid disease. Endocrinol Metab Clin North Am 1987; 16:431.
- Kung AW, Lau KS, Kohn LD. Epitope mapping of tsh receptor-blocking antibodies in Graves' disease that appear during pregnancy. J Clin Endocrinol Metab 2001; 86:3647.
- 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; 54:365.
- Kampmann JP, Johansen K, Hansen JM, Helweg J. Propylthiouracil in human milk. Revision of a dogma. Lancet 1980; 1:736.
- Azizi F, Khoshniat M, Bahrainian M, Hedayati M. Thyroid function and intellectual development of infants nursed by mothers taking methimazole. J Clin Endocrinol Metab 2000; 85:3233.
- Momotani N, Yamashita R, Makino F, et al. Thyroid function in wholly breast-feeding infants whose mothers take high doses of propylthiouracil. Clin Endocrinol (Oxf) 2000; 53:177.
- American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108:776.
- Momotani N, Hisaoka T, Noh J, et al. Effects of iodine on thyroid status of fetus versus mother in treatment of Graves' disease complicated by pregnancy. J Clin Endocrinol Metab 1992; 75:738.
- Senior B, Chernoff HL. Iodide goiter in the newborn. Pediatrics 1971; 47:510.
- Roti E, Minelli R, Gardini E, et al. Controversies in the treatment of thyrotoxicosis. Adv Endocrinol Metab 1994; 5:429.
- Kuy S, Roman SA, Desai R, Sosa JA. Outcomes following thyroid and parathyroid surgery in pregnant women. Arch Surg 2009; 144:399.
- Zimmerman D. Fetal and neonatal hyperthyroidism. Thyroid 1999; 9:727.
- 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; 90:6093.
- 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; 99:1040.
- Huel C, Guibourdenche J, Vuillard E, et al. Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter. Ultrasound Obstet Gynecol 2009; 33:412.
- Nachum Z, Rakover Y, Weiner E, Shalev E. Graves' disease in pregnancy: prospective evaluation of a selective invasive treatment protocol. Am J Obstet Gynecol 2003; 189:159.
- Kilpatrick S. Umbilical blood sampling in women with thyroid disease in pregnancy: Is it necessary? Am J Obstet Gynecol 2003; 189:1.
- 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; 55:108.
- 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; 93:3985.
- Therapeutic options
- Beta blockers
- - Possible teratogenicity
- - Choice of drug
- - Dose and monitoring
- - Nursing
- T4 administration
- FETAL HYPERTHYROIDISM
- Measurement of maternal antibodies
- - Fetal blood sampling
- Neonatal hyperthyroidism
- POSTPARTUM ISSUES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Fetal monitoring