What are the trimester‑specific target ranges for thyroid stimulating hormone (TSH) and free thyroxine (free T4) in a pregnant woman?

Trimester-Specific TSH and Free T4 Target Ranges in Pregnancy

Pregnant women require trimester-specific TSH reference ranges that are lower than non-pregnant values, with first trimester targets of 0.1–2.5 mIU/L, second trimester 0.2–3.0 mIU/L, and third trimester 0.3–3.0 mIU/L, though recent evidence suggests these may need adjustment based on gestational week and population. 1

First Trimester TSH Targets

• The American Thyroid Association originally recommended TSH 0.1–2.5 mIU/L for the entire first trimester, though this has been subject to significant controversy and revision 1, 2

• TSH levels vary significantly by gestational week within the first trimester, with median TSH at 4–6 weeks (2.15 mIU/L) being significantly higher than at 7–12 weeks (1.47 mIU/L), suggesting non-pregnant reference ranges may be appropriate for weeks 4–6 3

• Population-specific differences exist, with Chinese pregnant women showing upper TSH limits much higher than 2.5 mIU/L in the first trimester, and only 30% of women with TSH >2.5 mIU/L in first trimester maintaining TSH >3.0 mIU/L by 20 weeks 3

• The 2017 ATA revised guidelines recommend an upper TSH limit 0.5 mIU/L below the preconception value, or 4.0 mIU/L when population-specific ranges are unavailable, acknowledging the controversy around the stricter 2.5 mIU/L cutoff 2

• Mediterranean population data (Crete, Greece) established first trimester TSH reference range of 0.05–2.53 μIU/mL, demonstrating geographic variation in normal ranges 4

Second Trimester TSH Targets

• The recommended TSH range for second trimester is 0.2–3.0 mIU/L, reflecting continued but less pronounced thyroid stimulation compared to first trimester 1

• Mediterranean population data showed second trimester TSH reference range of 0.18–2.73 μIU/mL, slightly lower than guideline recommendations 4

Third Trimester TSH Targets

• The recommended TSH range for third trimester is 0.3–3.0 mIU/L, as thyroid hormone requirements remain elevated but stabilize 1

• Only 20.3% of women with first trimester TSH >2.5 mIU/L maintained TSH >3.0 mIU/L by 30 weeks gestation, suggesting natural normalization occurs in many cases 3

Physiological Basis for Lower TSH in Pregnancy

• Normal pregnancy causes subnormal TSH concentrations with normal free T4 levels due to hCG's structural similarity to TSH, which directly stimulates the thyroid gland 5

• Using non-pregnant TSH reference ranges (0.45–4.5 mIU/L) in pregnant women is inappropriate and will miss significant thyroid dysfunction 5

• Median TSH concentrations decrease significantly starting from the seventh week of gestation, with no significant change in free T4 during the first trimester 3

Free T4 Considerations

• Free T4 should be maintained in the upper normal range during pregnancy, particularly when treating hypothyroidism 1

• Median free T4 levels are not significantly altered in the first trimester, unlike TSH which shows marked changes 3

Monitoring Protocol for Pre-Existing Hypothyroidism

• For pregnant women with pre-existing hypothyroidism, check TSH every 4 weeks until stable, then every trimester 5

• Thyroxine requirements are higher in pregnancy, necessitating dose adjustments in women already on levothyroxine 1

Critical Clinical Implications

• Using the ATA's original 2.5 mIU/L cutoff in Chinese populations resulted in 27.8% prevalence of subclinical hypothyroidism, compared to 4.0% using population-derived reference intervals (upper limit 4.87 mIU/L), demonstrating the risk of overdiagnosis with overly strict criteria 3

• Maternal hypothyroidism is associated with increased risk of low birth weight, fetal distress, and impaired neuropsychological development, making accurate diagnosis and treatment essential 1

• 6.8% of women in the first trimester and 5.9% in the second trimester had TSH higher than population-specific upper reference limits, indicating the clinical relevance of trimester-specific ranges 4

Common Pitfalls to Avoid

• Avoid applying uniform TSH limits across the entire first trimester, as gestational week significantly affects TSH levels and may lead to misclassification and unnecessary treatment 6

• Do not use non-pregnant reference ranges for pregnant women after 7 weeks gestation, as this will fail to identify thyroid dysfunction 5, 3

• Recognize that population-specific and geographic variations exist, requiring local reference ranges when possible rather than universal application of guideline cutoffs 3, 2, 4