In a 31‑year‑old woman with overt primary hypothyroidism and iron‑deficiency anemia who had a negative serum β‑human chorionic gonadotropin (β‑hCG) three weeks ago and now has a positive result indicating early intra‑uterine pregnancy, what is the appropriate initial evaluation and management, including thyroid hormone dose adjustment, prenatal vitamin supplementation, and follow‑up?

Management of Newly Confirmed Pregnancy in a Woman with Overt Hypothyroidism and Iron-Deficiency Anemia

Immediately increase levothyroxine by 25–30% (approximately 25 µg if currently on 75–100 µg) on the day pregnancy is confirmed, then check TSH and free T4 within one week, targeting first-trimester TSH <2.5 mIU/L to prevent irreversible fetal neurocognitive impairment. 1, 2

Thyroid Hormone Dose Adjustment

• Increase levothyroxine dose by 25–50% immediately upon positive pregnancy test, as thyroid hormone requirements rise substantially during pregnancy 1, 2
• Target TSH <2.5 mIU/L throughout the first trimester; maintain TSH in trimester-specific reference ranges thereafter 3, 2, 4
• Check TSH and free T4 every 4 weeks during the first trimester, then every 4–6 weeks throughout pregnancy until a stable dose is achieved 1, 2
• Untreated or inadequately treated overt hypothyroidism increases risk of preeclampsia, low birth weight, miscarriage, and irreversible offspring neurocognitive deficits 3, 5, 6, 4
• Levothyroxine must be taken 30–60 minutes before breakfast on an empty stomach, separated from iron supplements by at least 2–4 hours to prevent absorption interference 1, 2

Monitoring Schedule

• Week 1 post-confirmation: TSH and free T4 1, 2
• Every 4 weeks during first trimester: TSH and free T4 1, 2
• Every 6–8 weeks during second and third trimesters once stable 3, 2
• Adjust levothyroxine dose in 12.5–25 µg increments based on TSH results 2

Iron-Deficiency Anemia Management

• Prescribe 60–120 mg elemental iron daily (e.g., ferrous sulfate 325 mg = 65 mg elemental iron, taken 1–2 times daily) for confirmed iron-deficiency anemia 3
• Iron must be taken at least 2–4 hours after levothyroxine (e.g., with lunch or dinner) to avoid competitive absorption 1, 2
• Recheck hemoglobin and hematocrit in 4 weeks; expect a 1 g/dL rise in hemoglobin or 3% rise in hematocrit if treatment is effective 3
• If anemia does not respond after 4 weeks despite compliance, measure MCV, RDW, and serum ferritin to exclude thalassemia trait, sickle cell trait, or other causes 3
• Once hemoglobin normalizes for gestational age, reduce iron dose to 30 mg/day for maintenance 3
• Hypothyroidism itself is associated with lower serum ferritin and worsened iron-deficiency anemia; optimizing thyroid replacement may improve iron status 7

Anemia Thresholds by Trimester

• First trimester: Hemoglobin <11.0 g/dL or hematocrit <33% 3
• Second trimester: Hemoglobin <10.5 g/dL or hematocrit <32% 3
• Third trimester: Hemoglobin <11.0 g/dL or hematocrit <33% 3
• Refer to physician if hemoglobin <9.0 g/dL or hematocrit <27% for further evaluation 3

Prenatal Vitamin Supplementation

• Prescribe prenatal vitamins containing 400–800 µg folic acid daily, starting immediately 1
• Ensure prenatal vitamin includes 27 mg elemental iron (Institute of Medicine recommendation for pregnancy) 3
• If prenatal vitamin iron content is insufficient to treat anemia, add supplemental iron as outlined above 3
• Separate prenatal vitamins containing calcium from levothyroxine by at least 4 hours to prevent thyroid hormone malabsorption 1, 2

Medication Timing to Optimize Absorption

• Levothyroxine: 30–60 minutes before breakfast, on empty stomach 1, 2
• Iron supplement: At least 2–4 hours after levothyroxine (e.g., lunchtime or with dinner) 1, 2
• Prenatal vitamin (if contains calcium): Evening, separated from both levothyroxine and iron 1
• Constipation (common with iron) impairs levothyroxine absorption; treat with polyethylene glycol 3350 (17 g daily), increase dietary fiber to 25–30 g/day, and maintain hydration 1

Follow-Up Schedule

• Week 1: TSH, free T4, confirm levothyroxine dose increase 1, 2
• Week 4: Repeat TSH, free T4; recheck hemoglobin/hematocrit to assess iron response 3, 2
• Weeks 8,12 (first trimester): TSH, free T4 1, 2
• Every 6–8 weeks (second and third trimesters): TSH once stable 3, 2
• 4 weeks after any levothyroxine dose change: TSH and free T4 2
• Continue iron supplementation throughout pregnancy and 2–3 months postpartum if anemia persists 3

Critical Pitfalls to Avoid

• Do not delay levothyroxine dose increase; even subclinical hypothyroidism in the first trimester causes irreversible fetal cognitive impairment 1, 4
• Do not take iron and levothyroxine together; simultaneous administration reduces levothyroxine absorption by up to 40% 1, 2
• Do not target mid-normal TSH; first-trimester TSH must be <2.5 mIU/L to ensure adequate fetal thyroid hormone supply 3, 1, 2
• Do not assume prenatal vitamins alone treat iron-deficiency anemia; therapeutic iron doses (60–120 mg elemental iron) are required for confirmed anemia 3
• Do not overlook adrenal insufficiency before escalating levothyroxine in patients with unexplained hypotension or hyponatremia; assess morning cortisol if indicated 1
• Reduce levothyroxine to pre-pregnancy dose immediately after delivery to prevent postpartum thyrotoxicosis; recheck TSH 4–8 weeks postpartum 2

Postpartum Considerations

• Reduce levothyroxine to pre-pregnancy dose on the day of delivery 2
• Check TSH 4–8 weeks postpartum to confirm appropriate dosing 2
• Continue iron supplementation for 2–3 months postpartum if anemia persisted through the third trimester 3
• Monitor for postpartum thyroiditis, especially in women with autoimmune thyroid disease 5