Physicians should be aware of the changes in thyroid physiology during pregnancy. Pregnancy is associated with reversible changes in thyroid physiology that should be noted before diagnosing thyroid abnormalities (see Fig. 31.12 for pregnancy associated changes in TBG, total T4, hCG, TSH, and free T4) (403). Women with a history of hypothyroidism often require increased thyroxine replacement during pregnancy, and patients should have thyroid function tests performed at the first prenatal visit and during each trimester thereafter. Evidence suggests that optimal fetal and infant neurodevelopmental outcomes may require careful titration of replacement thyroxine that meets the frequently increased requirements of pregnancy (413,414).
Reproductive Effects of Hyperthyroidism to TBG. Relative serum concentration changes throughout pregnancy highlighting a fall in TSH associated with an increase in hCG early in pregnancy and a fall in free T4 as TBG levels rise during pregnancy. hCG, human chorionic gonadotropin; TSH, thyroid-stimulating hormone; TBG, thyroid-binding globulin, total T4, total thyroxine; free T4, free thyroxine. (Based on data from Brent GA. Maternal thyroid function: interpretation of thyroid function tests in pregnancy. Clin Obstet Gynecol 1997;40:3–15.)
Postpartum, women should return to their prepregnancy dosage of levothyroxine and have a follow-up TSH checked 6 to 8 weeks postpartum.
High levels of TSAb (TSI) in women with Graves disease are associated with fetal-neonatal hyperthyroidism (415,416). Despite both the inhibition and elevation of gonadotropins seen in thyrotoxicosis, most women remain ovulatory and fertile (387,417). Severe thyrotoxicosis can result in weight loss, menstrual cycle irregularities, and amenorrhea. An increased risk of spontaneous abortion is noted in women with thyrotoxicosis. An increased incidence of congenital anomalies, particularly choanal atresia and possibly aplasia cutis, can occur in the offspring of women treated with methimazole (404,405,408).
Autoimmune hyperthyroid Graves disease may improve spontaneously, in which case antithyroid drug therapy may be reduced or stopped. TSHRAb production may persist for several years after radical radioactive iodine therapy or surgical treatment for hyperthyroid Graves disease. In this circumstance, there is a risk of exposing a fetus to TSHRAb. Fetal–neonatal hyperthyroidism is observed in 2% to 10% of pregnancies occurring in mothers with a current or previous diagnosis of Graves disease, secondary to the transplacental passage of maternal TSHRAb. This is a serious condition with a 16% neonatal mortality rate and a risk of intrauterine fetal death, stillbirth, and skeletal developmental abnormalities, such as craniosynostosis. Caution against overtreatment with antithyroid medication is warranted, as these medications may cross the placenta in sufficient quantities to induce fetal goiter. Guidelines for TSHRAb testing during pregnancy in women with previously treated Graves disease are found in Table 31.15. Fetal goiters and the associated fetal hypo-or hyperthyroid status were diagnosed accurately in mothers with Graves disease using a combination of fetal ultrasonography of the thyroid with Doppler, fetal heart rate monitoring, bone maturation, and maternal TSHRAb and antithyroid drug status (418).
Postpartum Thyroid Postpartum thyroid dysfunction is much more common than recognized; it is often difficult