In a pregnant woman in her third trimester, what is the desired thyroid‑stimulating hormone (TSH) target and how should levothyroxine be managed if the TSH exceeds this target, both for patients with known hypothyroidism and for those newly diagnosed?

Third Trimester TSH Target in Pregnancy

In the third trimester of pregnancy, the TSH target should be ≤3.0 mIU/L, and levothyroxine dosing should be adjusted to maintain TSH within this trimester-specific range while monitoring every 4 weeks until stable. 1, 2, 3

Trimester-Specific TSH Targets

• The upper limit of normal TSH in the third trimester is 3.0 mIU/L, which is higher than the first trimester target of ≤2.5 mIU/L but represents the physiologic increase in TSH that occurs as pregnancy progresses 1, 3, 4
• Some guidelines define subclinical hypothyroidism in the third trimester as TSH >3.0 mIU/L with normal free T4, while overt hypothyroidism is TSH >10 mIU/L with low free T4 3
• The 2017 American Thyroid Association guidelines recommend using population-specific reference ranges when available, or defaulting to an upper limit of 4.0 mIU/L if local data are unavailable, though the more conservative 3.0 mIU/L cutoff remains widely used 4

Management Algorithm for Known Hypothyroidism

Patients Already on Levothyroxine Pre-Pregnancy

• Increase the levothyroxine dose by 25-50% (or 30% as an alternative approach) immediately upon pregnancy confirmation, as more than 50% of women with pre-existing hypothyroidism require dose escalation during pregnancy 2, 3
• Monitor TSH every 4 weeks after any dose adjustment until TSH is stable within the trimester-specific range (≤3.0 mIU/L in third trimester) 1, 2
• Adjust levothyroxine in 12.5-25 mcg increments based on TSH results to maintain the target range 1, 2
• Reduce levothyroxine to pre-pregnancy levels immediately after delivery and recheck TSH 4-8 weeks postpartum 2

Newly Diagnosed Hypothyroidism in Third Trimester

For TSH ≥10 mIU/L (Overt Hypothyroidism):

• Start levothyroxine at 1.6 mcg/kg/day to rapidly normalize thyroid function 2, 5
• Alternatively, use 2.33 mcg/kg/day based on evidence showing this achieves euthyroidism within 5-6 weeks in newly diagnosed overt hypothyroidism during pregnancy 5
• Monitor TSH every 4 weeks and adjust dose until TSH ≤3.0 mIU/L 2

For TSH <10 mIU/L but >3.0 mIU/L (Subclinical Hypothyroidism):

• Start levothyroxine at 1.0 mcg/kg/day per FDA labeling 2
• For TSH 4.2-10 mIU/L specifically, evidence supports starting 1.42 mcg/kg/day, which achieves target TSH in 89% of patients without additional adjustments 5
• For TSH 3.0-4.2 mIU/L, use 1.20 mcg/kg/day 5
• Monitor TSH every 4 weeks until stable within target range 2

Critical Monitoring Parameters

• Measure both TSH and free T4 to distinguish subclinical from overt hypothyroidism and guide therapy 6, 2
• TSH should be checked every 4 weeks during dose titration in pregnancy, which is more frequent than the 6-8 week interval used in non-pregnant patients 2
• Once stable, continue monitoring TSH at minimum once per trimester 1
• Free T4 should be maintained in the upper half of the normal range to ensure adequate fetal thyroid hormone supply 1

Rationale for Treatment

• Untreated or inadequately treated maternal hypothyroidism increases risk of preeclampsia, low birth weight, preterm delivery, and neurodevelopmental deficits in the offspring 1, 2, 3
• Maternal thyroid hormone is critical for fetal brain development, particularly in the first and second trimesters, but adequate levels remain important throughout pregnancy 1
• The fetus relies on maternal thyroid hormone transfer, especially before fetal thyroid function is fully established 3

Common Pitfalls to Avoid

• Do not use non-pregnancy TSH reference ranges (0.45-4.5 mIU/L) in pregnant patients, as this will result in undertreatment 6, 3, 4
• Do not wait to increase levothyroxine dose until TSH rises above target—proactive dose increases at pregnancy confirmation prevent maternal hypothyroidism 2, 3
• Do not target mid-normal TSH values; aim for the lower half of the trimester-specific range to ensure adequate maternal and fetal thyroid hormone levels 1
• Avoid checking TSH too frequently (more often than every 4 weeks during titration) as levothyroxine requires this interval to reach steady state 2
• Do not forget to reduce levothyroxine to pre-pregnancy dose immediately postpartum, as continued high doses will cause iatrogenic hyperthyroidism 2

Special Considerations

• In areas with iodine deficiency, TSH reference ranges may differ, and local population-specific ranges should be used when available 4, 7, 8
• Some Asian populations show higher TSH reference ranges in pregnancy (third trimester upper limit 5.4-7.6 mIU/L in certain studies), though international guidelines still recommend the 3.0 mIU/L cutoff 7, 8
• Women with positive anti-TPO antibodies have higher risk of progression to overt hypothyroidism (4.3% per year vs 2.6% in antibody-negative patients) and warrant closer monitoring 6