How should overt hypothyroidism, subclinical hypothyroidism, and overt hyperthyroidism be managed in a first‑trimester pregnant woman, including medication choices, dosing, and monitoring targets?

Management of Gestational Thyroid Disease in the First Trimester

Overt Hypothyroidism in First-Trimester Pregnancy

Initiate levothyroxine immediately at 100-150 mcg daily (or 2.0-2.4 mcg/kg/day) as soon as overt hypothyroidism is diagnosed in pregnancy, targeting TSH <2.5 mIU/L in the first trimester. 1, 2, 3

Immediate Treatment Protocol

• Start levothyroxine at full replacement doses (100-150 mcg daily) without gradual titration, as rapid normalization is critical for fetal neurodevelopment 2
• For women already on levothyroxine pre-pregnancy, increase the dose by 30-50% immediately upon pregnancy confirmation 4, 2, 3
• If inadequately treated hypothyroidism is discovered during pregnancy, double the levothyroxine dose on at least three days per week to rapidly achieve euthyroidism 2

TSH and Free T4 Targets

• Target TSH <2.5 mIU/L throughout the first trimester 1, 2, 3
• Maintain free T4 in the upper half of the normal reference range 5, 1
• Use trimester-specific TSH reference ranges for monitoring 1, 2

Monitoring Schedule

• Check TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 1
• Levothyroxine requirements increase as early as week 5 of gestation, with a median onset at week 8 and plateau by week 16 4
• The mean levothyroxine requirement increases 47% during the first half of pregnancy 4

Critical Safety Considerations

• Rule out adrenal insufficiency before initiating levothyroxine, especially in suspected central hypothyroidism, as thyroid hormone can precipitate adrenal crisis 6
• Untreated overt hypothyroidism causes preeclampsia, low birth weight, and permanent neurodevelopmental deficits in the child 5, 1, 3
• Even isolated maternal hypothyroxinemia (low T4 with normal TSH) requires treatment due to risks to fetal brain development 1

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Subclinical Hypothyroidism in First-Trimester Pregnancy

Treat subclinical hypothyroidism (elevated TSH with normal free T4) immediately with levothyroxine during pregnancy, targeting TSH <2.5 mIU/L in the first trimester. 5, 3

Treatment Rationale

• Subclinical hypothyroidism is associated with increased risks of preeclampsia, low birth weight, and impaired fetal neurodevelopment 5
• Treatment should begin immediately upon diagnosis, not delayed for repeat testing 5, 3

Dosing Strategy

• Start levothyroxine at 1.6 mcg/kg/day for new-onset hypothyroidism 6
• For women with pre-existing subclinical hypothyroidism on levothyroxine, increase dose by 25-50% immediately upon pregnancy confirmation 4, 7
• Adjust dose by 12.5-25 mcg increments based on TSH results every 4 weeks 6

Monitoring Protocol

• Check TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 1
• Target TSH <2.5 mIU/L in first trimester, with free T4 in upper-normal range 5, 1

Evidence Quality Considerations

• Although treatment of mild maternal thyroid hypofunction remains somewhat controversial due to lack of definitive RCT evidence showing improved outcomes, the minimal risk of levothyroxine treatment and mounting evidence of associations with adverse outcomes support treatment 3
• The potential harms of untreated subclinical hypothyroidism (preeclampsia, preterm labor, lower child cognitive scores) outweigh the negligible risks of levothyroxine therapy 3

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Overt Hyperthyroidism in First-Trimester Pregnancy

Treat overt hyperthyroidism in pregnancy with propylthiouracil (PTU) as first-line during the first trimester, switching to methimazole after the first trimester if needed. 3

Medication Selection by Trimester

• Use propylthiouracil (PTU) exclusively during the first trimester due to less severe teratogenicity compared to methimazole 3
• Switch to methimazole after the first trimester if continued antithyroid medication is needed 3
• Methimazole has more severe teratogenic effects and should be avoided in the first trimester 3

Distinguishing Gestational Transient Thyrotoxicosis from Graves' Disease

• Gestational transient thyrotoxicosis is associated with high hCG levels during the first trimester and nearly always accompanied by hyperemesis gravidarum 7
• This condition typically resolves spontaneously and does not require antithyroid medication 7, 3
• Graves' disease requires treatment with antithyroid medications throughout pregnancy 3
• Measure TSH receptor antibodies to distinguish Graves' disease from gestational transient thyrotoxicosis 3

Dosing and Monitoring Strategy

• Use monotherapy with antithyroid drugs (not block-and-replace regimens) 7
• Adjust dose based on free T4 in the high-normal range and TSH in the low-normal range to minimize risk of fetal hypothyroidism 7
• Monitor free T4 levels, as transplacental passage of maternal TSH receptor stimulating antibodies may cause fetal hyperthyroidism 7

Preconception Counseling for Women with Graves' Disease

• Women should delay pregnancy for at least 6 months following radioactive iodine to minimize radiation effects and ensure normal thyroid hormone levels 3
• Definitive therapy (surgery or radioactive iodine) may be considered prior to pregnancy, though medical management during pregnancy is equally effective 7

Critical Pitfalls to Avoid

• Never use methimazole in the first trimester due to severe teratogenic effects 3
• Do not treat gestational transient thyrotoxicosis with antithyroid drugs, as it resolves spontaneously 7, 3
• Avoid excessive antithyroid drug dosing that could cause fetal hypothyroidism 7