Total T4 rise in pregnancy: a relook?

BACKGROUND

Total T4 (TT4) measurement is preferred to free T4 (FT4) especially in last part of pregnancy. Guidelines by American Thyroid Association, European Thyroid Association and Endocrine Society state that TT4 increases 1.5 times pre-pregnant levels after week 16 of pregnancy. However, this is based on a small study conducted 40 years ago which used radioimmunoassay for determination in changes in TT4.

MATERIALS AND METHODS

A cross-sectional study was undertaken to find reference interval for thyroid function in different trimester of pregnancy with special reference to look at the degree of elevation of TT4 as compared to non-pregnant women. Two hundred non-pregnant women (excluding oral contraceptive users) and 600 pregnant women (200 from each trimester) aged 18-40 years were consecutively recruited starting from around 6th week of pregnancy having confirmed singleton pregnancy diagnosed at 8th week by ultrasound. The exclusion criteria included: (1) a personal or family history of thyroid disease; (2) presence of goiter or nodule confirmed by ultrasound; (3) anti-TPO antibody positive state (titre > 35 IU/ml). All subjects were tested for urinary spot iodine concentration and those with UIC < 150 μg/L were excluded. Finally, thyroid function tests (TSH, FT4, TT4, TT3) of 168 non-pregnant women and 163, 153 and 148 women at 1st, 2nd and 3rd trimester respectively were analysed..

RESULTS

Total T4 (mean ± SD, μg/dl) in non pregnant women and in different trimesters was 8.95 ± 1.71, 9.71 ± 2.39, 12.11 ± 1.55, 11.83 ± 1.49 respectively. Rise in TT4 occurred between 10-18th week. The mean TT4 in second trimester increased by 25% as compared with the value at 6-9th week and by 35% as compared to non-pregnant value.

CONCLUSION

Rise in total T4 in second trimester pregnancy is only around 25% as compared to first trimester value and 35% than the non-pregnant value. Hence multiplying non-pregnant T4 value by 1.5 may actually over-diagnose maternal hypothroxinemia and lead to inappropriate diagnosis and treatment of isolated maternal hypothyroxinemia in a significant proportion of subjects.