BACKGROUND:

Thyroid hormone requirement increases 20-40% during gestation. Women with treated hypothyroidism must increase their l-T(4) in pregnancy to prevent maternal hypothyroidism, although how this should be accomplished is unclear.

METHODS:

We prospectively enrolled 60 women with treated hypothyroidism seeking pregnancy. Once pregnant, women were randomized to increase l-T(4) by either two tablets/wk (group A) or three tablets/wk (group B). Thyroid function was tested biweekly through midpregnancy and at 30 wk gestation. Levothyroxine was adjusted to maintain goal TSH concentrations. The primary objective was to assess efficacy in preventing maternal hypothyroidism and the safety of this intervention.

RESULTS:

Forty-eight women completed the protocol. Increasing the l-T(4) dose once pregnant (regardless of study arm) prevented TSH elevation over 5.0 mIU/liter throughout the first trimester and replicated physiological changes of pregnancy. The early l-T(4) increase caused TSH suppression below 0.5 mIU/liter in eight of 25 women in group A compared with 15 of 23 women in group B (P < 0.01). This risk was significantly increased in athyreotic patients [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.1-11.1], those with prepregnancy TSH less than 1.5 mIU/liter (OR = 4.6; 1.3-16.2), and those receiving prepregnancy l-T(4) doses of 100 microg/d or more (OR = 7.2; 1.7-30.6). However, if a trimester-specific TSH lower reference range of 0.1 mIU/liter was used, only two patients (8%) in group A required dose reduction. TSH testing every 4 wk identifies 92% of abnormal values.

CONCLUSIONS:

A two-tablet increase in l-T(4) initiated at confirmation of pregnancy significantly reduces the risk of maternal hypothyroidism during the first trimester and mimics normal physiology. Monitoring TSH every 4 wk through midgestation is recommended.