A variety of endocrine disorders can complicate pregnancy and vice versa. Diabetes mellitus is the most prevalent and is discussed in Chapter 52. Thyroid disorders are also common, and a number of less common endocrinopathies—for example, pheochromocytoma—can have devastating effects on pregnancy outcome. The pathogenesis of many endocrinopathies is disordered autoimmunity. And as with most organ-specific autoimmune disorders, clinical manifestations of endocrinopathies result from a complex interplay among genetic, environmental, and endogenous factors that activate the immune system against target cells (Weetman, 2004). In many cases, a nonspecific event such as a viral infection initiates an organ-specific response with subsequent immune-mediated glandular destruction. Also, studies implicating cells transferred between mother and fetus during pregnancy in development of autoimmune disease decades later represent a new investigative frontier (Muraji and associates, 2008; Rust and Bianchi, 2009).
Taken in aggregate, thyroid disorders are common in young women. There is an intimate relationship between maternal and fetal thyroid function, and drugs that affect the maternal thyroid also affect the fetal gland. Thyroid autoantibodies have been associated with increased early pregnancy wastage, and uncontrolled thyrotoxicosis and untreated hypothyroidism are both associated with adverse pregnancy outcomes (Männistö and colleagues, 2009). Finally, there is evidence that the severity of autoimmune thyroid disorders is ameliorated during pregnancy, only to be exacerbated postpartum.
Thyroid Physiology and Pregnancy
The impact of pregnancy on maternal thyroid physiology is substantial. Changes in the structure and function of the gland sometimes cause confusion in the diagnosis of thyroid abnormalities. These are discussed in greater detail in Chapter 5, Endocrine System, and normal hormone level changes are found in the Appendix. Maternal serum concentration of thyroid-binding globulin is increased concomitantly with total or bound thyroid hormone levels (Fig. 5-16). Thyrotropin, or thyroid-stimulating hormone (TSH), currently plays a central role in screening and diagnosis of many thyroid disorders. Serum thyrotropin levels in early pregnancy decrease because of thyroid stimulation from the weak TSH effects of human chorionic gonadotropin (hCG) (Grossman and associates, 1997). TSH does not cross the placenta. At the same time, hCG serum levels are maximal for the first 12 weeks, free thyroxine levels increase to suppress pituitary thyrotropin secretion (Fig. 53-1). Accordingly, thyrotropin-releasing hormone (TRH) is undetectable in maternal serum. Fetal serum TRH is detectable beginning at midpregnancy, but does not increase.
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 and colleagues, 2005; Dashe and co-workers, 2005.)