Endocrinopathies are closely related to pregnancy for several reasons. One example is the gestational proclivity for prodigious hormone secretion, which is perhaps best illustrated by placental lactogen in diabetes. This is the most common endocrinopathy encountered in pregnancy and discussed in Chapter 57. Pregnancy is also interrelated with some endocrinopathies that are at least partially due to autoimmune dysregulation. Clinical manifestations result from complex interplay among genetic, environmental, and endogenous factors that activate the immune system against targeted cells within endocrine organs. In one extraordinary interaction, studies have implicated maternal organ engraftment by fetal cells transferred during pregnancy. These cells later provoke antibody production, tissue destruction, and autoimmune endocrinopathies.
Taken in aggregate, these disorders are common in young women and thus frequently encountered in pregnancy. Maternal and fetal thyroid function are intimately related, and drugs that affect the maternal thyroid affect the fetal gland. Moreover, thyroid autoantibodies are associated with increased rates of early pregnancy wastage. Uncontrolled thyrotoxicosis and untreated hypothyroidism are both associated with adverse pregnancy outcomes. Last, evidence suggests that the severity of some autoimmune thyroid disorders may be ameliorated during pregnancy, only to be exacerbated postpartum.
Thyroid Physiology and Pregnancy
Maternal thyroid changes are substantial, and normally altered gland structure and function can sometimes be confused with thyroid abnormalities. These alterations are discussed in detail in Chapter 4 (p. 71), and normal serum hormone level values are found in the Appendix (p. 1230). First, maternal serum concentrations of thyroid binding globulin are increased concomitantly with total or bound thyroid hormone levels. Second, thyrotropin, also called thyroid-stimulating hormone (TSH), plays a central role in screening and diagnosis of many thyroid disorders, but levels change throughout pregnancy. Notably, TSH receptors are cross stimulated, albeit weakly, by massive quantities of human chorionic gonadotropin (hCG) secreted by placental trophoblast. Because TSH does not cross the placenta, it has no direct fetal effects. During the first 12 weeks of gestation, when maternal hCG serum levels are maximal, thyroid hormone secretion is stimulated. The resulting greater serum free thyroxine (T4) levels act to suppress hypothalamic thyrotropin-releasing hormone (TRH) and in turn limit pituitary TSH secretion (Fig. 61-1). Accordingly, TRH is undetectable in maternal serum. Conversely, in fetal serum, beginning at midpregnancy, TRH becomes detectable, but levels are static and do not rise.
Gestational-age-specific values for serum thyroid-stimulating hormone (TSH) levels (black lines) and free thyroxine (T4) levels (blue lines). Data were derived from 17,298 women tested during pregnancy. For each color, the dark solid lines represent the 50th percentile, whereas the upper and lower light lines represent the 2.5th and 97.5th percentiles, respectively. (Data from Casey, 2005; Dashe, 2005.)
Throughout pregnancy, maternal thyroxine is transferred to the fetus (...