A pregnant woman in her second trimester complains of heat intolerance and palpitations. Physical examination reveals a slightly enlarged, non-tender thyroid gland, and a normal cardiac exam. The serum thyroxine (T4) level is increased; however, the serum thyroid-stimulating hormone (TSH) is normal. Which of the following best explains the laboratory findings in this patient?

The total serum thyroxine (T4) represents the sum of the T4 bound to thyroid-binding globulin (TBG) and the free T4. An increased total T4 may be due to an increase in TBG or an increase in free T4, the latter leading to signs of thyrotoxicosis. A decreased total T4 may be secondary to a reduction in TBG or in free T4, the latter leading to signs of hypothyroidism. In a euthyroid state, one-third of the binding sites on TBG are occupied by T4. An increase in estrogen (pregnancy, bih control pills) increases the synthesis of TBG. Since one-third of the binding sites on TBG will be occupied, the T4 bound to the additional TBG increases the total serum T4. The addition of extra TBG does not alter the free T4 level because of the equilibrium between the serum concentration of T4 and thyroid gland T4 production. Since the free T4 level is normal, there is no stimulus to release thyroid-stimulating hormone (TSH) from the pituitary gland. Regarding the patient's enlarged thyroid gland, heat intolerance, and palpitations, these are normal findings in pregnancy and do not indicate an overactive thyroid gland. Estrogen is increased (not decreased) in pregnancy. The serum free T4 is normal in pregnancy. This explains why the serum TSH is normal in the presence of an elevated serum T4, which reflects the increase in TBG normally occurring in pregnancy. The increase in progesterone during pregnancy has no effect on TBG levels.