Nineteen hypothyroid women were observed before and throughout their pregnancies. Thyroid-stimulating hormone (TSH) levels were measured every two weeks during the first trimester and monthly thereafter. The dose of levothyroxine was increased to maintain the TSH concentration at preconception values throughout pregnancy. An increase in the levothyroxine dose was necessary during 17 of 20 pregnancies; one woman with a history of thyroid cancer required a decrease in the dose at 26 weeks' gestation. The mean levothyroxine requirement increased by 47% during the first half of pregnancy. The median time at which a dose increase was required was eight weeks' gestation (although increased requirements were seen as early as the fifth week), and the dosage requirement reached a plateau by week 16. This increased dose requirement persisted until delivery.

Comment: Hypothyroidism during pregnancy has been associated with increased fetal mortality and impaired cognitive development of the infant. Previous studies have shown that maternal thyroid hormone requirements increase during pregnancy; however, the timing and amount of levothyroxine adjustment required has not been previously investigated. Based on the results of the present study, the authors suggest that women with hypothyroidism increase their levothyroxine dose by approximately 30% as soon as pregnancy is confirmed. Thereafter, TSH levels should be monitored and the levothyroxine dose adjusted accordingly.

However, in women with normal laboratory tests for thyroid function who are being treated empirically with thyroid hormone (see Gaby AR. Altern Med Rev 2004;9:157-179), the situation is more complicated. Many of these women presumably have subtle tissue resistance to thyroid hormone, either genetic or acquired. If a woman's fetus does not have tissue resistance to thyroid hormone, then increasing the dose of thyroid hormone during pregnancy would expose the fetus to a hyperthyroid environment, which can have deleterious effects on the fetus, including miscarriage. On the other hand, some women had been infertile until they began empirical therapy with thyroid hormone; in those women, failure to increase the dose during pregnancy could potentially result in a miscarriage. In my female patients with normal laboratory tests for thyroid function whose infertility problems appeared to be corrected with thyroid hormone, I have usually not changed the dose during pregnancy, and maternal and fetal outcomes have so far been acceptable. Of course, each case should be considered on an individual basis.

Alexander EK, et al. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med 2004;351:241-249.

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