What are the trimester‑specific TSH reference ranges in pregnancy and how should abnormal TSH levels be managed?

TSH Reference Ranges and Management in Pregnancy

Trimester-Specific TSH Reference Ranges

The 2017 American Thyroid Association guidelines recommend using population-specific reference ranges when available, or alternatively, an upper TSH limit of 4.0 mIU/L if local data are unavailable 1, 2. However, this represents a significant revision from earlier stricter cutoffs and reflects ongoing controversy in the field 2.

Evidence-Based Trimester-Specific Ranges

The most appropriate approach is to use institution-specific, trimester-specific reference ranges because thyroid function varies substantially across populations due to ethnicity, iodine status, body mass index, and assay methodology 3. Published population-specific ranges demonstrate this variability:

• First trimester: Ranges vary from 0.05-2.53 mIU/L 4 to 0.07-3.96 mIU/L 5 to 0.38-2.91 mIU/L 6
• Second trimester: Ranges vary from 0.18-2.73 mIU/L 4 to 0.27-4.53 mIU/L 5 to 0.72-4.22 mIU/L 6
• Third trimester: Range of 0.48-5.40 mIU/L has been reported 5

These population-specific ranges differ substantially from the older fixed ATA limits (first trimester 0.1-2.5 mIU/L, second trimester 0.2-3.0 mIU/L), which would misclassify a significant proportion of pregnant women 6, 2.

Free T4 Reference Ranges

Free T4 also requires trimester-specific interpretation 1:

• First trimester: 9.16-18.12 pmol/L to 12.18-19.48 pmol/L 6, 5
• Second trimester: 8.67-16.21 pmol/L to 9.64-17.39 pmol/L 6, 5
• Third trimester: 7.80-13.90 pmol/L 5

Management of Abnormal TSH in Pregnancy

When TSH is Elevated (Hypothyroidism)

For pregnant women with elevated TSH, immediate levothyroxine treatment is essential to prevent preeclampsia, low birth weight, placental abruption, fetal death, and permanent neurodevelopmental deficits in the child 1.

Pre-existing Hypothyroidism

• Increase levothyroxine by 25-30% (approximately 25 µg for a patient on 75 µg) immediately upon pregnancy confirmation, without waiting for TSH results 1
• Target TSH <2.5 mIU/L in the first trimester, then within trimester-specific ranges thereafter 1
• Check TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 7
• Levothyroxine requirements typically increase by 25-50% during pregnancy 7

Newly Diagnosed Hypothyroidism in Pregnancy

• Start levothyroxine monotherapy at 1.6 mcg/kg/day for TSH ≥10 mIU/L 7
• Never use T3 supplementation during pregnancy, as it provides inadequate fetal thyroid hormone delivery 7
• First and second trimester treatment is critical because the fetus relies entirely on maternal thyroid hormone for normal cognitive development 1

Subclinical Hypothyroidism (Elevated TSH, Normal Free T4)

Subclinical hypothyroidism during pregnancy is associated with increased risks of preeclampsia, low birth weight, and impaired neuropsychological development in offspring 1. Treatment with levothyroxine is recommended to normalize TSH 1.

Isolated Hypothyroxinemia (Normal TSH, Low Free T4)

Measure thyroid peroxidase (TPO) antibodies to exclude autoimmune thyroid disease 1. If TPO antibodies are positive, this reclassifies the condition as subclinical hypothyroidism requiring levothyroxine therapy 1. Maternal hypothyroxinemia has been associated with alterations in fetal neuropsychological development and increased risk of fetal loss 1.

When TSH is Suppressed

For pregnant women on levothyroxine with suppressed TSH:

• Reduce levothyroxine dose by 25-50 mcg if TSH <0.1 mIU/L 7
• Reduce by 12.5-25 mcg if TSH 0.1-0.45 mIU/L 7
• Prolonged TSH suppression increases risk for atrial fibrillation, osteoporosis, and cardiovascular complications 7

Monitoring Protocol

Evaluate thyroid function every trimester to adjust levothyroxine dose, with the goal of maintaining free T4 in the high-normal range using the lowest possible medication dose 1. For women with pre-existing hypothyroidism on stable doses, check TSH every trimester after stabilization 7.

Critical Pitfalls to Avoid

• Do not wait for TSH results before increasing levothyroxine in a pregnant woman with known hypothyroidism—fetal harm can occur before maternal symptoms appear 1
• Do not mistake isolated hypothyroxinemia (normal TSH, low free T4) for subclinical hypothyroidism (elevated TSH, normal free T4)—the latter requires levothyroxine treatment 1
• Do not use fixed universal TSH cutoffs—calculate institution-specific reference intervals or use population-specific data 6, 3
• Do not discontinue levothyroxine during pregnancy, as untreated maternal hypothyroidism increases risk of preeclampsia, gestational hypertension, stillbirth, and premature delivery 7
• Avoid TSH targets >2.5 mIU/L in the first trimester, as even subclinical hypothyroidism is associated with adverse pregnancy outcomes 1

Consequences of Inadequate Treatment

Untreated or inadequately treated hypothyroidism during pregnancy causes:

• Preeclampsia 1
• Low birth weight 1
• Placental abruption 1
• Fetal death 1
• Permanent neurodevelopmental deficits and cognitive impairment in offspring 1
• Increased risk of congenital cretinism (mental retardation and neuropsychological defects) in iodine-deficient areas 1

Women who are adequately treated before conception or receive early treatment in pregnancy do not experience increased perinatal morbidity 1.