Managing hyperthyroidism in pregnancy: current perspectives

Abstract

Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves' disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6-10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the consequences of untreated or inadequately treated disease, and finally how to treat overt hyperthyroidism in pregnancy.

Keywords: Graves’ disease; antithyroid drug; fetal programming; hyperthyroidism; pregnancy; thyroid.

Figure 1

Age-specific IR per 100,000 py for the most common types of hyperthyroidism in Denmark (Graves’ disease, multinodular toxic goiter, and solitary toxic adenoma). Note: Reproduced with permission from Carlé A, Pedersen IB, Knudsen N, et al. Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study. Eur J Endocrinol. 2011;164(5):801–809. Abbreviations: IR, incidence rate; py, person-years.

Figure 2

IR of maternal hyperthyroidism in 3-month intervals before, during, and after the first pregnancy leading to birth of a live-born child from 1999 to 2008 in a Danish population-based study of 403,958 women. Notes: The dashed horizontal line indicates the overall IR of maternal hyperthyroidism in women aged 15–45 years in the study period from 1997 to 2010. *Indicates significant difference from the overall IR. Republished with permission of the Endocrine Society, from Andersen SL, Olsen J, Carlé A, Laurberg P. Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance with some other autoimmune diseases: a Danish population-based study. J Clin Endocrinol Metab. 2015;100(3):1164–1171; permission conveyed through Copyright Clearance Center, Inc. Abbreviation: IR, incidence rate.

Figure 3

Reference limits for the diagnosis of hyperthyroidism in early pregnancy established with the Dimension Vista (Siemens) automatic immunoassay. Notes: (A) and (B) illustrate the 2.5 percentile for TSH and the 97.5 percentile for fT4 with (95% CI), respectively. Dashed horizontal lines indicate the reference limit in nonpregnant adults as reported by the manufacturer. Republished with permission of the Endocrine Society, from Laurberg P, Andersen SL, Hindersson P, Nohr EA, Olsen J. Dynamics and predictors of serum TSH and fT4 reference limits in early pregnancy: a study within the Danish National Birth Cohort. J Clin Endocrinol Metab. 2016;101(6):2484–2492; permission conveyed through Copyright Clearance Center, Inc. Abbreviations: TSH, thyroid-stimulating hormone; CI, confidence interval; fT4, free T4.

Figure 4

Adjusted OR with 95% CI for subtypes of birth defects in 1,097 children exposed to MMI/CMZ and 564 children exposed to PTU in early pregnancy versus the reference group of 811,730 children not exposed to ATD. Notes: Musculoskeletal defects were various types of abdominal wall defects, integumentary defects included aplasia cutis and face and neck defects included preauricular sinus and cysts. Associations marked with gray circles were not statistically significant. Republished with permission of the Endocrine Society, from 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(11):4373–4381; permission conveyed through Copyright Clearance Center, Inc. Abbreviations: OR, odds ratio; CI, confidence interval; MMI, methimazole; CMZ, carbimazole; PTU, propylthiouracil; ATD, antithyroid drug.