Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes
- 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
Overt hyperthyroidism (low thyroid-stimulating hormone [TSH], elevated free thyroxine [T4] and/or triiodothyronine [T3]) is relatively uncommon during pregnancy, occurring in 0.1 to 0.4 percent of all pregnancies [1,2]. The diagnosis of pregnant women with hyperthyroidism parallels that of nonpregnant women and men but presents some unique problems. The clinical manifestations, diagnosis, and causes of hyperthyroidism during pregnancy are presented here. The treatment of hyperthyroidism during pregnancy and other aspects of thyroid disease during pregnancy are discussed separately. (See "Hyperthyroidism during pregnancy: Treatment" and "Overview of thyroid disease in pregnancy".)
THYROID PHYSIOLOGY DURING NORMAL PREGNANCY
The diagnosis of thyroid disease during pregnancy requires an understanding of the changes in thyroid physiology and thyroid function tests that accompany normal pregnancy. These changes are reviewed briefly below and in more detail separately. (See "Overview of thyroid disease in pregnancy", section on 'Thyroid adaptation during normal pregnancy'.)
To meet the increased metabolic needs during a normal pregnancy, there are changes in thyroid physiology that are reflected in altered thyroid function tests. These changes include the following:
●Thyroid hormone-binding globulin (TBG) excess results in high serum total T4 and total T3 concentrations but not high serum free T4 or free T3 concentrations.
●High serum human chorionic gonadotropin (hCG) concentrations during early pregnancy and even higher concentrations in women with hyperemesis gravidarum or multiple pregnancies may result in transient subclinical or rarely overt hyperthyroidism.
- Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010; 31:702.
- Lo JC, Rivkees SA, Chandra M, et al. Gestational thyrotoxicosis, antithyroid drug use and neonatal outcomes within an integrated healthcare delivery system. Thyroid 2015; 25:698.
- Davis LE, Lucas MJ, Hankins GD, et al. Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol 1989; 160:63.
- Sheffield JS, Cunningham FG. Thyrotoxicosis and heart failure that complicate pregnancy. Am J Obstet Gynecol 2004; 190:211.
- 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.
- Millar LK, Wing DA, Leung AS, et al. Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism. Obstet Gynecol 1994; 84:946.
- Kriplani A, Buckshee K, Bhargava VL, et al. Maternal and perinatal outcome in thyrotoxicosis complicating pregnancy. Eur J Obstet Gynecol Reprod Biol 1994; 54:159.
- Luewan S, Chakkabut P, Tongsong T. Outcomes of pregnancy complicated with hyperthyroidism: a cohort study. Arch Gynecol Obstet 2011; 283:243.
- Casey BM, Dashe JS, Wells CE, et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol 2006; 107:337.
- Medici M, Timmermans S, Visser W, et al. Maternal thyroid hormone parameters during early pregnancy and birth weight: the Generation R Study. J Clin Endocrinol Metab 2013; 98:59.
- Haddow JE, Craig WY, Neveux LM, et al. Implications of High Free Thyroxine (FT4) concentrations in euthyroid pregnancies: the FaSTER trial. J Clin Endocrinol Metab 2014; 99:2038.
- Medici M, Korevaar TI, Schalekamp-Timmermans S, et al. Maternal early-pregnancy thyroid function is associated with subsequent hypertensive disorders of pregnancy: the generation R study. J Clin Endocrinol Metab 2014; 99:E2591.
- 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.
- Alexander EK, Pearce EN, Brent GA, et al. 2016 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum. Thyroid 2017.
- Dashe JS, Casey BM, Wells CE, et al. Thyroid-stimulating hormone in singleton and twin pregnancy: importance of gestational age-specific reference ranges. Obstet Gynecol 2005; 106:753.
- Stricker R, Echenard M, Eberhart R, et al. Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age-specific reference intervals. Eur J Endocrinol 2007; 157:509.
- Gilbert RM, Hadlow NC, Walsh JP, et al. Assessment of thyroid function during pregnancy: first-trimester (weeks 9-13) reference intervals derived from Western Australian women. Med J Aust 2008; 189:250.
- Fitzpatrick DL, Russell MA. Diagnosis and management of thyroid disease in pregnancy. Obstet Gynecol Clin North Am 2010; 37:173.
- Lambert-Messerlian G, McClain M, Haddow JE, et al. First- and second-trimester thyroid hormone reference data in pregnant women: a FaSTER (First- and Second-Trimester Evaluation of Risk for aneuploidy) Research Consortium study. Am J Obstet Gynecol 2008; 199:62.e1.
- Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol 2013; 1:238.
- 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.
- Vos XG, Smit N, Endert E, et al. Frequency and characteristics of TBII-seronegative patients in a population with untreated Graves' hyperthyroidism: a prospective study. Clin Endocrinol (Oxf) 2008; 69:311.
- Ota H, Amino N, Morita S, et al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease. Clin Endocrinol (Oxf) 2007; 67:41.
- Glinoer D, de Nayer P, Bourdoux P, et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab 1990; 71:276.
- Goodwin TM, Montoro M, Mestman JH, et al. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin Endocrinol Metab 1992; 75:1333.
- Yamazaki K, Sato K, Shizume K, et al. Potent thyrotropic activity of human chorionic gonadotropin variants in terms of 125I incorporation and de novo synthesized thyroid hormone release in human thyroid follicles. J Clin Endocrinol Metab 1995; 80:473.
- Kimura M, Amino N, Tamaki H, et al. Gestational thyrotoxicosis and hyperemesis gravidarum: possible role of hCG with higher stimulating activity. Clin Endocrinol (Oxf) 1993; 38:345.
- Hershman JM. Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. Thyroid 1999; 9:653.
- Yoshimura M, Pekary AE, Pang XP, et al. Thyrotropic activity of basic isoelectric forms of human chorionic gonadotropin extracted from hydatidiform mole tissues. J Clin Endocrinol Metab 1994; 78:862.
- Walkington L, Webster J, Hancock BW, et al. Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblastic disease. Br J Cancer 2011; 104:1665.
- Rodien P, Brémont C, Sanson ML, et al. Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin. N Engl J Med 1998; 339:1823.
- Smits G, Govaerts C, Nubourgh I, et al. Lysine 183 and glutamic acid 157 of the TSH receptor: two interacting residues with a key role in determining specificity toward TSH and human CG. Mol Endocrinol 2002; 16:722.
- THYROID PHYSIOLOGY DURING NORMAL PREGNANCY
- CLINICAL FEATURES
- Clinical manifestations
- Pregnancy complications
- Laboratory findings
- ESTABLISHING THE CAUSE
- Our approach
- Graves' disease
- hCG-mediated hyperthyroidism
- - Gestational transient thyrotoxicosis
- - Hyperemesis gravidarum
- - Trophoblastic hyperthyroidism
- - Familial gestational hyperthyroidism
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS