Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism

N Engl J Med. 2004 Jul 15;351(3):241-9. doi: 10.1056/NEJMoa040079.


Background: Hypothyroidism during pregnancy has been associated with impaired cognitive development and increased fetal mortality. During pregnancy, maternal thyroid hormone requirements increase. Although it is known that women with hypothyroidism should increase their levothyroxine dose during pregnancy, biochemical hypothyroidism occurs in many. In this prospective study we attempted to identify precisely the timing and amount of levothyroxine adjustment required during pregnancy.

Methods: Women with hypothyroidism who were planning pregnancy were observed prospectively before and throughout their pregnancies. Thyroid function, human chorionic gonadotropin, and estradiol were measured before conception, approximately every two weeks during the first trimester, and monthly thereafter. The dose of levothyroxine was increased to maintain the thyrotropin concentration at preconception values throughout pregnancy.

Results: Twenty pregnancies occurred in 19 women and resulted in 17 full-term births. An increase in the levothyroxine dose was necessary during 17 pregnancies. The mean levothyroxine requirement increased 47 percent during the first half of pregnancy (median onset of increase, eight weeks of gestation) and plateaued by week 16. This increased dose was required until delivery.

Conclusions: Levothyroxine requirements increase as early as the fifth week of gestation. Given the importance of maternal euthyroidism for normal fetal cognitive development, we propose that women with hypothyroidism increase their levothyroxine dose by approximately 30 percent as soon as pregnancy is confirmed. Thereafter, serum thyrotropin levels should be monitored and the levothyroxine dose adjusted accordingly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Chorionic Gonadotropin / blood
  • Drug Administration Schedule
  • Estradiol / blood
  • Female
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / drug therapy*
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / drug therapy*
  • Prospective Studies
  • Thyrotropin / blood
  • Thyroxine / administration & dosage*
  • Thyroxine / blood
  • Thyroxine / therapeutic use


  • Chorionic Gonadotropin
  • Estradiol
  • Thyrotropin
  • Thyroxine