Thyroid gland

Maternal thyroid hormone is critical for normal embryonic and fetal development. Among the hepatic proteins stimulated by the elevated circulating levels of estrogen in pregnancy is thyroid-binding globulin (TBG). The increased TBG results in a decrease in circulating free T₃ and T₄ that will stimulate thyroid-stimulating hormone (TSH) production by the pituitary gland, thereby increasing the production of thyroxine by the thyroid gland. The alfa subunit of human chorionic gonadotropin (hCG) also appears to stimulate the thyroid gland, thereby assuring a timely increase in thyroxine production with pregnancy onset.

Interpretation of thyroid tests in pregnancy can be confusing because of the increased TBG. Total T₃ and T₄ will be elevated as will T₃ resin uptake (T₃RU), the indirect measure of total thyroxine binding capacity. Because of these changes, thyroid testing in pregnancy should rely on measurements of serum TSH and/or free T₃ and T₄.

Gastrointestinal tract

Pregnancy is a potentially diabetogenic state. It is a state of relative hyperinsulinism with peripheral insulin resistance. The high maternal levels of estrogen, progesterone and human placental lactogen (hPL) cause hypertrophy, hyperplasia and hypersecretion of insulin by the beta islet cells of the pancreas. Still, many pregnant women show prolonged hyperglycemia after meals. In addition, most pregnant women exhibit: (i) exaggerated insulin release in response to glucose infusion; (ii) reduced peripheral uptake of glucose; and (iii) suppressed glucagon secretion. Taken together, these traits characterize insulin resistance. The mechanism(s) for insulin resistance in pregnancy are not well understood. The growth hormone-like activity of hPL may be responsible. In addition, hPL may also promote lipolysis and liberation of free fatty acids that facilitate tissue resistance to insulin. These metabolic changes ensure a continuous supply of glucose for transfer to the fetus. Women at increased lifetime risk for developing type 2 diabetes mellitus (DM) will often develop a condition known as gestational diabetes mellitus (GDM). The presence of GDM confers a sevenfold risk of future type 2 DM. The same mechanisms that ensure a continuous supply of fetal glucose produce an “accelerated starvation” profile during fasting. Fasted pregnant women are relatively hypoglycemic and have higher circulating free fatty acids, triglycerides and cholesterol. Prolonged fasting or persistent vomiting in pregnant women can rapidly lead to ketonemia.

High maternal levels of circulating estrogens increase the synthesis of hepatic proteins. These include procoagulants, bile acids and multiple hormone binding proteins. The procoagulants most markedly elevated are factors I (fibrinogen), VII, VIII, IX and X. The higher circulating concentrations of clotting cascade proteins protect the mother from excessive blood loss at the time of delivery; however, they also predispose pregnant and postpartum women to venous thrombosis and embolism. Estrogens also stimulate the cytochrome P450 oxidative pathway in the liver. This increases the production of steroid precursors and can dramatically alter drug metabolism. The latter effect necessitates careful monitoring of the maternal plasma drug levels of many commonly used therapeutics. Most notable are the anticonvulsants and antibiotics.

The calcium requirements of the developing fetal and neonatal skeleton produce a profound maternal calcium stress during pregnancy and lactation. Maternal plasma parathyroid hormone (PTH) concentrations rise despite a minimal decrease in circulating free calcium. Intestinal absorption of calcium is enhanced by an increase in circulating 1,25-dihydroxyvitamin D₃, the active metabolite of vitamin D. 1,25-(OH)₂-D₃ increases for two reasons: (i) PTH increases the hepatic synthesis of 25-(OH)-D₃, and (ii) the activity of 1α-hydroxylase increases in pregnancy. In nonpregnant women and men, conversion of 25-(OH)-D₃ to the 1,25 active form is limited by the activity of 1α-hydroxylase, the final converting enzyme in D₃ metabolism. 1α-hydroxylase is typically present only in the kidney but, in pregnancy, it is produced by both the decidua and placenta. This ensures an adequate amount of active D₃ to optimize dietary calcium absorption during pregnancy. If dietary calcium intake is adequate, minimal mobilization of maternal bone calcium occurs. If it is not, fetal and neonatal skeletal mineralization will proceed at the expense of maternal bone density.

Progesterone relaxes smooth muscle and thereby affects all parts of the gastrointestinal tract during pregnancy. Gastric emptying is delayed, as is movement of digested material along the remainder of the tract. Gallbladder emptying is slower and bile tends to sludge in the bile duct and common duct. Minor disorders of the gastrointestinal tract are very common in pregnancy. These include nausea, vomiting, constipation and heartburn.