Be ready to increase levothyroxine in women with hypothyroidism

Because levothyroxine requirements increase as early as the fifth week of gestation–which is often before a first obstetric visit—and because maternal hypothyroidism can lead to fetal cognitive deficits and even death, women with hypothyroidism may need to increase their dose of levothyroxine by about 30% as soon as pregnancy is confirmed.

The recommendation comes from a prospective study involving 19 women and 17 full-term births. The researchers found that a mean increase of 47% in levothyroxine dose was required in 17 of 20 pregnancies (85%) to maintain thyrotropin concentrations at prepregnancy values. The increase was required within the first half of the pregnancies, often by 8 weeks' gestation, and remained necessary until delivery.

The increase in thyrotropin occurred whether or not the women had a history of thyroid cancer. Women who became pregnant by means of assisted reproductive technologies had even greater increases in thyrotropin early in gestation than those who conceived spontaneously. They also had significantly higher concentrations of serum estradiol at 7 weeks' gestation. Increased estradiol is what many experts believe is at the core of why extra levothyroxine is required. Estradiol causes an increase in serum concentrations of thyroxine-binding globulin, which, in turn, decreases the thyroid hormone-binding ratio.

The necessary increase in levothyroxine translates into about two daily doses per week. The author of an editorial in the same issue of the Journal posits that increasing the dose by 25 to 50 µg daily and requesting thyroid-function testing within the following 4 to 6 weeks makes practical sense. The author also suggests that the findings of the latest study support the need to measure serum thyroxine, thyrotropin, or both, in all women of childbearing age to detect unrecognized thyroid failure before pregnancy occurs.

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

Toft A. Increased levothyroxine requirements in pregnancy—Why, when, and how much? N Engl J Med. 2004;351:292-294.