Abstract and Introduction
Thyroid diseases affect up to 5% of all pregnancies. Adverse pregnancy and neonatal outcomes are increased by maternal thyroid disease and adequate treatment is thought to reduce these risks. Hypothyroidism is commonly treated with levothyroxine, with pregnancy increasing levothyroxine requirements in most women treated for hypothyroidism. Hyperthyroidism is often treated with antithyroid drugs in pregnancy. However, they are not completely safe to use during pregnancy as methimazole increases risk of neonatal malformations and propylthiouracil increases risk of maternal hepatotoxicity. Propylthiouracil is recommended to be used during the first trimester and switch to methimazole is recommended thereafter to reduce risk of hepatotoxicity. The treatment goal for hypothyroidism and hyperthyroidism is to achieve euthyroidism quickly and maintain it throughout pregnancy. Autoimmune thyroiditis and isolated maternal hypothyroxinemia do not currently warrant treatment during pregnancy, unless hypothyroidism ensues. Treatment of thyroid nodules and differentiated thyroid cancer can generally be safely postponed until after delivery.
The normal physiological changes in thyroid function during pregnancy have been well characterized: the concentrations of thyroid binding globulins increase up to mid-pregnancy due to high estrogen levels; serum thyrotropin (TSH) levels decrease in early pregnancy due to direct thyroidal stimulation by human chorionic gonadotropin; thyroid size and thyroid hormone production increase throughout pregnancy and iodine requirements increase due to increased renal clearance and losses to the feto-placental unit. Pregnancy can be considered as a stress test of maternal thyroid function where women with limited thyroid reserve may develop hypothyroidism.
Diagnosing thyroid diseases during pregnancy can be difficult as the clinical signs and symptoms mimic those of pregnancy. Hypothyroidism is associated with weight gain, fatigue and constipation while hyperthyroidism causes nausea and increased appetite (Table 1).[3,4] Current recommendations suggest targeted TSH screening for women at high risk for thyroid disease before or during early pregnancy (Table 2), with other thyroid function tests used to confirm the diagnoses and disease severity.[2,5] However, reference ranges of TSH or free thyroxine (fT4) obtained from non-pregnant populations do not reflect normal values in pregnant women because of their physiologic changes in thyroid function.[2,5] Several studies have attempted to create trimester- and population-specific reference intervals for TSH concentrations in healthy pregnant women.[6–8] When such reference ranges are not available, women with serum TSH over 2.5 mIU/l in the first and over 3.0 mIU/l in the second and third trimesters of pregnancy are diagnosed with hypothyroidism.[2,5] The magnitude of TSH elevation and measurements of fT4 are used to distinguish between subclinical and overt hypothyroidism.[2,5] Notably, the lower reference limit of TSH concentrations is also decreased in pregnant women, so euthyroid women can be diagnosed as hyperthyroid if non-pregnant reference ranges are used. Repeat laboratory sampling within a week might be advisable in cases with isolated increases in TSH or decreases in fT4 in pregnancy (especially borderline values) to confirm diagnoses. In one study, only 56% of pregnant women had repeatedly elevated TSH with normal fT4 concentration when two samples were taken a week apart in early pregnancy.
The gold standard in measuring fT4 concentrations during pregnancy is equilibrium dialysis coupled with mass spectrometry, but such assays are not readily available in all clinical laboratories. Commonly employed immunoassays often give biased estimates of fT4 concentrations due to interference by the high concentrations of thyroid binding globulins, although fT4 concentrations measured with most immunoassays exhibit the typical pattern related to pregnancy with elevations in early pregnancy and decreases thereafter. However, although results within an assay are valid, the results between assays are generally not comparable and therefore it is recommended to establish assay- and trimester-specific reference values for fT4.[2,5,11] Some recommend overcoming this problem by measuring total thyroxine. However, total thyroxine reference range is wider than that of fT4 due to the underlying variability of thyroid binding globulin, which may lead to reduced diagnostic accuracy especially among subjects with borderline test results. Additionally, although the non-pregnant reference range of total thyroxine can be adapted to the second and third trimesters of pregnancy by multiplying the range by 1.5, there are no total thyroxine reference ranges for the first trimester of pregnancy when the thyroid binding globulin concentrations increase. Measuring fT4 might therefor be more useful in pregnant patients when trying to distinguish between overt and subclinical thyroid diseases. However, clinical decision on diagnosis and treatment of hypothyroidism or hyperthyroidism should mostly be based on serum TSH concentrations and overall clinical picture and symptoms.[2,5]
As diagnosing thyroid diseases during pregnancy may be difficult, adequate preconception diagnostics and management of thyroid diseases is crucial. Pregnant women with thyroid diseases should be diagnosed and their treatment managed preferably in multidisciplinary clinics, where obstetricians, endocrinologists, pediatricians and other healthcare professionals can jointly work together to reduce risks of adverse pregnancy and neonatal outcomes associated with thyroid diseases.
Expert Rev Endocrinol Metab. 2013;8(6):537-547. © 2013 Expert Reviews Ltd.