Total T4 rise in pregnancy: a relook?

Area of Science:

• Endocrinology
• Reproductive Medicine
• Clinical Chemistry

Background:

• Current guidelines recommend Total T4 (TT4) over Free T4 (FT4) during pregnancy, citing a 1.5-fold increase in TT4 levels after 16 weeks.
• This recommendation is based on outdated research from 40 years ago using radioimmunoassay methods.
• A need exists for updated reference intervals for thyroid function tests during pregnancy.

Purpose of the Study:

• To establish reference intervals for thyroid function tests across pregnancy trimesters.
• To accurately assess the degree of TT4 elevation in pregnant women compared to non-pregnant individuals.
• To re-evaluate the commonly used 1.5-fold multiplier for TT4 levels in pregnancy.

Main Methods:

• A cross-sectional study involving 600 pregnant women (200 per trimester) and 200 non-pregnant women aged 18-40.
• Exclusion criteria included thyroid disease history, goiter/nodules, positive anti-TPO antibodies, and low urinary iodine concentration (<150 μg/L).
• Thyroid function tests (TSH, FT4, TT4, TT3) were analyzed in 168 non-pregnant women and 163, 153, and 148 pregnant women in the 1st, 2nd, and 3rd trimesters, respectively.

Main Results:

• Mean TT4 levels (μg/dL) were 8.95±1.71 in non-pregnant women, and increased to 9.71±2.39, 12.11±1.55, and 11.83±1.49 in the 1st, 2nd, and 3rd trimesters, respectively.
• The significant rise in TT4 occurred between weeks 10-18 of gestation.
• Mean TT4 in the second trimester showed a 25% increase from the first trimester and a 35% increase compared to non-pregnant values.

Conclusions:

• Total T4 levels increase by approximately 25% from the first trimester and 35% from non-pregnant levels during the second trimester.
• Multiplying non-pregnant TT4 values by 1.5 may lead to overdiagnosis of maternal hypothyroxinemia.
• Current diagnostic criteria may result in inappropriate treatment for isolated maternal hypothyroxinemia.