What is the recommended management of overt and subclinical hypothyroidism in pregnancy, including levothyroxine dosing, target thyroid‑stimulating hormone levels, iodine supplementation, and postpartum follow‑up?

Management of Hypothyroidism in Pregnancy

Pregnant women with overt or subclinical hypothyroidism require immediate levothyroxine treatment with trimester-specific TSH targets, increased dosing compared to non-pregnant states, and close monitoring every 4 weeks to prevent maternal and fetal complications. 1, 2, 3

---

Overt Hypothyroidism in Pregnancy

Initial Levothyroxine Dosing

• Start levothyroxine at 2.33 μg/kg/day for newly diagnosed overt hypothyroidism (elevated TSH with low free T4) during pregnancy to rapidly achieve euthyroidism and minimize fetal risk 3
• For women with pre-existing hypothyroidism on levothyroxine who become pregnant, increase the dose by 25-50% immediately upon pregnancy confirmation 1
• The full replacement dose approach (rather than gradual titration) is justified in pregnancy because the benefit-risk ratio strongly favors rapid normalization of thyroid function for fetal neurodevelopment 2, 3

TSH Target Ranges by Trimester

• First trimester: TSH ≤2.5 mIU/L 1, 3
• Second and third trimesters: TSH ≤3.0 mIU/L 1, 3
• Maintain free T4 in the upper half of the normal reference range throughout pregnancy 2, 4

Monitoring Protocol

• Recheck TSH and free T4 every 4 weeks during pregnancy until stable, then at minimum once per trimester 1, 2
• Adjust levothyroxine dose by 12.5-25 μg increments based on TSH results to maintain trimester-specific targets 1
• Most women achieve euthyroidism within 5-6 weeks when appropriate initial dosing is used 3

---

Subclinical Hypothyroidism in Pregnancy

Treatment Indications

All pregnant women with subclinical hypothyroidism (elevated TSH with normal free T4) require levothyroxine treatment regardless of symptoms to prevent adverse pregnancy outcomes including preeclampsia, low birth weight, miscarriage, and impaired fetal neurocognitive development 1, 4, 3

Initial Levothyroxine Dosing Based on TSH Level

• TSH 2.5-4.2 mIU/L (first trimester) or >3.0-4.2 mIU/L (second/third trimester): Start 1.20 μg/kg/day 3
• TSH >4.2-10 mIU/L: Start 1.42 μg/kg/day 3
• These weight-based doses achieve target TSH in approximately 89% of patients without requiring additional adjustments 3

Special Consideration: Isolated Maternal Hypothyroxinemia

• Pregnant women with low free T4 and normal TSH should be treated with levothyroxine despite the normal TSH, as this pattern (isolated maternal hypothyroxinemia) is associated with impaired fetal neuropsychological development and increased risk of fetal wastage 2
• This differs from non-pregnant management where normal TSH typically indicates no treatment is needed 2

---

Anti-TPO Antibody-Positive Women

Treatment Approach

• Women who are anti-TPO antibody-positive with any degree of TSH elevation during pregnancy require levothyroxine treatment 1, 4
• Anti-TPO positivity indicates autoimmune thyroid disease with a 4.3% annual progression risk to overt hypothyroidism (versus 2.6% in antibody-negative women) 1, 4
• These women have higher risk of miscarriage and premature delivery even with normal thyroid function 1

---

Iodine Supplementation

Recommendations

• Pregnant and lactating women should receive 250 μg of iodine daily (150 μg baseline requirement plus 100 μg supplement) to ensure adequate thyroid hormone production 1
• Iodine deficiency during pregnancy can cause maternal and fetal hypothyroidism even in women without pre-existing thyroid disease 1
• Avoid excessive iodine exposure (e.g., iodine-containing contrast agents when possible) as this can transiently affect thyroid function tests 1

---

Critical Safety Considerations

Pre-Treatment Assessment

• Before initiating levothyroxine in suspected central hypothyroidism, rule out concurrent adrenal insufficiency by checking morning cortisol and ACTH 1, 4
• If adrenal insufficiency is present, start hydrocortisone at least one week before levothyroxine to prevent life-threatening adrenal crisis 1, 4

Medication Interactions

• Levothyroxine must be taken on an empty stomach, 30-60 minutes before breakfast for optimal absorption 1
• Separate levothyroxine from iron supplements, calcium, and antacids by at least 4 hours as these significantly reduce absorption 1, 5
• Proton pump inhibitors, atrophic gastritis, and H. pylori infection decrease levothyroxine absorption and may require higher doses 5

---

Postpartum Management

Dose Adjustment

• Reduce levothyroxine dose to pre-pregnancy levels immediately after delivery in women with pre-existing hypothyroidism 1
• For women with hypothyroidism newly diagnosed during pregnancy, recheck TSH and free T4 at 6 weeks postpartum to determine if continued treatment is necessary 2
• Approximately 30-60% of TSH elevations during pregnancy may be transient and normalize postpartum 1, 6

Long-Term Monitoring

• Women with autoimmune thyroid disease require annual TSH monitoring as they remain at risk for progression to overt hypothyroidism 1, 4
• Recheck thyroid function before any subsequent pregnancy to optimize thyroid status prior to conception 1

---

Common Pitfalls to Avoid

• Never delay treatment while awaiting repeat TSH confirmation in pregnant women—the risk of untreated hypothyroidism to the fetus outweighs the minimal risk of levothyroxine therapy 2, 3
• Do not use standard non-pregnant TSH reference ranges (0.45-4.5 mIU/L) during pregnancy; trimester-specific targets are mandatory 1, 3
• Avoid undertreating by using overly conservative initial doses—pregnancy requires 25-50% higher levothyroxine doses than non-pregnant states, and gradual titration delays achieving euthyroidism 1, 3
• Do not discontinue levothyroxine during pregnancy even if TSH normalizes, as requirements typically increase throughout gestation 1
• Never start thyroid hormone replacement before ruling out adrenal insufficiency in women with suspected central hypothyroidism or hypophysitis 1, 4

---

Risks of Inadequate Treatment

• Maternal complications: preeclampsia, gestational hypertension, placental abruption, postpartum hemorrhage 1, 4
• Fetal/neonatal complications: miscarriage, stillbirth, premature delivery, low birth weight, impaired neurocognitive development with permanent deficits in IQ 1, 2, 4, 3
• The critical window for fetal brain development is the first and second trimesters when the fetus is entirely dependent on maternal thyroid hormone 1