What are the normal ranges for Thyroid-Stimulating Hormone (TSH), free Triiodothyronine (FT3), and free Thyroxine (FT4) levels during pregnancy?

Normal Thyroid Function Tests During Pregnancy

Trimester-Specific TSH Reference Ranges

TSH levels are significantly lower during pregnancy compared to non-pregnant women, with the most pronounced decrease occurring in the first trimester due to hCG-mediated thyroid stimulation. 1

First Trimester TSH Reference Ranges

• The upper limit of normal TSH in the first trimester should be 0.1-2.5 mIU/L according to international guidelines when institution-specific ranges are unavailable 2
• Population-specific studies show variation: Bulgarian pregnant women demonstrated a first trimester TSH range of 0.38-2.91 mIU/L 3
• Iranian pregnant women showed a first trimester TSH range of 0.2-3.9 mIU/L 4
• Indian pregnant women demonstrated mean first trimester TSH of 1.20 microIU/mL 5

Second Trimester TSH Reference Ranges

• International guidelines recommend 0.2-3.0 mIU/L for the second trimester when institution-specific ranges are unavailable 2
• Bulgarian pregnant women showed a second trimester TSH range of 0.72-4.22 mIU/L 3
• Iranian pregnant women demonstrated a second trimester TSH range of 0.5-4.1 mIU/L 4
• Indian pregnant women showed a second trimester TSH range of 0.1-5.5 microIU/mL with mean values of 2.12 microIU/mL 5

Third Trimester TSH Reference Ranges

• Iranian pregnant women demonstrated a third trimester TSH range of 0.6-4.1 mIU/L 4
• Indian pregnant women showed a third trimester TSH range of 0.5-7.6 microIU/mL with mean values of 3.30 microIU/mL 5
• TSH progressively increases throughout pregnancy, with the highest values typically seen in the third trimester 5

Free T4 (FT4) Reference Ranges During Pregnancy

First Trimester FT4 Ranges

• Bulgarian pregnant women demonstrated first trimester FT4 of 12.18-19.48 pmol/L 3
• FT4 values are typically at their highest in the first trimester due to hCG stimulation 2

Second Trimester FT4 Ranges

• Bulgarian pregnant women showed second trimester FT4 of 9.64-17.39 pmol/L 3
• FT4 progressively declines throughout pregnancy as thyroid-binding globulin increases 2

Third Trimester FT4 Ranges

• FT4 continues to decline in the third trimester compared to earlier pregnancy 2

Total T4 (TT4) Reference Ranges During Pregnancy

First Trimester TT4 Ranges

• Iranian pregnant women demonstrated first trimester TT4 of 8.2-18.5 μg/dL with mean values of 12.9±3 μg/dL 4
• Indian pregnant women showed mean first trimester T4 of 164.50 nmol/L 5

Second Trimester TT4 Ranges

• Iranian pregnant women showed second trimester TT4 of 10.1-20.6 μg/dL with mean values of 14.4±3.1 μg/dL 4
• Indian pregnant women demonstrated second trimester T4 range of 92.2-252.8 nmol/L with mean values of 165.80 nmol/L 5

Third Trimester TT4 Ranges

• Iranian pregnant women demonstrated third trimester TT4 of 9-19.4 μg/dL with mean values of 13.6±3.3 μg/dL 4
• Indian pregnant women showed third trimester T4 range of 108.2-219.0 nmol/L with mean values of 159.90 nmol/L 5

Total T3 (TT3) Reference Ranges During Pregnancy

First Trimester T3 Ranges

• Indian pregnant women demonstrated mean first trimester T3 of 1.85 nmol/L 5

Second Trimester T3 Ranges

• Indian pregnant women showed second trimester T3 range of 1.7-4.3 nmol/L with mean values of 2.47 nmol/L 5

Third Trimester T3 Ranges

• Indian pregnant women demonstrated third trimester T3 range of 0.4-3.9 nmol/L with mean values of 1.82 nmol/L 5

Physiological Mechanisms Explaining Pregnancy-Specific Changes

hCG-Mediated TSH Suppression

• Normal pregnancy causes subnormal TSH concentrations with normal free T4 levels due to hCG's structural similarity to TSH, which stimulates the thyroid gland 6, 1
• This physiological TSH suppression is most pronounced in the first trimester when hCG levels peak 2

Increased Thyroid-Binding Globulin

• Estrogen-induced increases in thyroid-binding globulin during pregnancy lead to elevated total T4 and T3 levels while free hormone levels remain relatively stable or decline 2
• This explains why total T4 increases substantially during pregnancy while free T4 may actually decrease 4

Increased Thyroid Hormone Requirements

• Most women with pre-existing hypothyroidism require a 25-50% increase in levothyroxine dose during pregnancy 7
• Women with preconception TSH of 1.2-2.4 mIU/L have a 50% likelihood of requiring levothyroxine dose increases during pregnancy 8
• Women with preconception TSH <1.2 mIU/L have only a 17.2% likelihood of requiring dose increases during pregnancy 8

Critical Importance of Population-Specific Reference Ranges

Factors Affecting Reference Ranges

• Substantial variation exists between different populations due to ethnicity, body mass index, iodine status, and socioeconomic factors 2
• Assay-specific differences contribute significantly to variation in thyroid function test results during pregnancy 2
• Bulgarian reference ranges differ substantially from American Thyroid Association and European Thyroid Association fixed limits 3

Clinical Implications of Using Incorrect Reference Ranges

• Even small subclinical variations in thyroid function are associated with detrimental pregnancy outcomes including low birth weight and pregnancy loss 2
• Using universal cutoff concentrations rather than institution-specific ranges can lead to misdiagnosis and inappropriate treatment 2
• Institutions should calculate their own pregnancy-specific reference intervals rather than relying on fixed universal cutoffs 2

Monitoring Recommendations for Pregnant Women

Women with Pre-Existing Hypothyroidism

• Check TSH every 4 weeks until stable, then every trimester 1
• Target preconception TSH should be <1.2 mIU/L to minimize the likelihood of requiring dose adjustments during pregnancy 8
• Women with preconception TSH of 1.2-2.4 mIU/L should anticipate a 50% probability of needing levothyroxine dose increases 8

Timing of Levothyroxine Dose Adjustments

• Women with hypothyroidism should increase their levothyroxine dose immediately upon confirmation of pregnancy to prevent fetal neurodevelopmental complications 7
• Inadequate treatment of hypothyroidism during pregnancy is associated with increased risk of preeclampsia and low birth weight 7

Common Pitfalls to Avoid

Misapplication of Non-Pregnant Reference Ranges

• Non-pregnant TSH reference ranges of 0.45-4.5 mIU/L are inappropriate for pregnant women and will miss significant thyroid dysfunction 6, 1
• Using non-pregnant upper TSH limits can delay diagnosis and treatment of hypothyroidism during pregnancy 2

Reliance on Universal Fixed Cutoffs

• Fixed TSH cutoffs fail to account for population-specific factors including ethnicity, iodine status, and body mass index 2
• Institutions must establish their own trimester-specific reference intervals to ensure accurate diagnosis 2, 3

Inadequate Preconception Optimization

• Women planning pregnancy should have TSH optimized to <1.2 mIU/L rather than accepting any value within the normal range 8
• Failure to optimize preconception TSH increases the likelihood of requiring urgent dose adjustments during early pregnancy when fetal neurodevelopment is most vulnerable 8