Should a pregnant female in the first trimester continue or stop Cytomel (liothyronine) while on Synthroid (levothyroxine) for stable thyroid function?

Should Cytomel Be Continued During First Trimester Pregnancy?

Cytomel (liothyronine/T3) should be discontinued immediately upon pregnancy confirmation, with the patient maintained on levothyroxine (Synthroid) monotherapy only. 1

Rationale for Discontinuation

The combination of levothyroxine plus liothyronine during pregnancy poses theoretical but significant risks to fetal neurodevelopment that outweigh any maternal benefit. 1 Here's why:

Physiological Concerns with T3 in Pregnancy

• Liothyronine (T3) crosses the placental barrier more readily than levothyroxine (T4), potentially exposing the fetus to supraphysiologic thyroid hormone levels during critical periods of brain development. 1

• The fetal thyroid gland does not begin functioning until 12-14 weeks gestation, making the fetus entirely dependent on maternal thyroid hormone during the first trimester—the most critical period for neurodevelopment. 2

• Maternal thyroxine (T4) is essential for fetal development during the first trimester, as it supplies thyroid hormone-dependent tissues, particularly the brain. 2

Evidence Against Combination Therapy in Pregnancy

• Professional societies do not recommend combination T4+T3 therapy during pregnancy due to theoretical dangers to fetal outcomes, despite its growing popularity in non-pregnant individuals. 1

• The FDA drug label for liothyronine states that thyroid hormones do not readily cross the placental barrier, but this applies more to T4 than T3, and minimal amounts are excreted in breast milk. 3

Immediate Management Steps

Medication Adjustment Protocol

• Discontinue Cytomel immediately and increase levothyroxine dose by approximately 30% (or two additional tablets per week) as soon as pregnancy is confirmed. 4, 5

• Levothyroxine requirements increase as early as the fifth week of gestation, with a mean increase of 47% during the first half of pregnancy, plateauing by week 16. 4

• This early dose increase prevents maternal hypothyroidism during the first trimester and mimics normal pregnancy physiology. 5

Monitoring Schedule

• Check TSH and free T4 every 4 weeks during the first half of pregnancy and at least once during the second half of pregnancy. 6, 5

• Target TSH should be maintained in the lower half of the normal reference range (ideally below 2.5 mIU/L in the first trimester) using trimester-specific reference intervals. 2

• Adjust levothyroxine dose to maintain TSH at preconception values throughout pregnancy. 4

Critical Risks of Inadequate Treatment

• Untreated or inadequately treated maternal hypothyroidism increases the risk of preeclampsia, low birth weight, and impaired fetal neuropsychological development. 7, 2

• After the 14th gestational week, fetal brain development may already be irreversibly affected by lack of thyroid hormones. 2

• Maternal hypothyroxinemia (low T4 with normal TSH) has been associated with impaired fetal cognitive development and increased fetal mortality. 7, 4

Why Levothyroxine Monotherapy Is Preferred

• Levothyroxine is safe during pregnancy and should not be discontinued—it is the standard of care for thyroid hormone replacement in pregnancy. 6

• The American College of Obstetricians and Gynecologists recommends levothyroxine treatment to return TSH to normal range, with dosage adjustments necessary for proper fetal neurologic development. 8, 6

• Women with hypothyroidism should have their thyroid function optimized before conception, with a target preconception TSH below 1.2 mIU/L. 7

Common Pitfalls to Avoid

• Do not continue combination therapy "because it has worked well" for the patient—pregnancy physiology fundamentally changes thyroid hormone requirements and fetal exposure risks. 1

• Do not wait for symptoms of hypothyroidism to develop before increasing levothyroxine—the critical window for fetal brain development occurs before symptoms manifest. 4, 2

• Do not use non-pregnant reference ranges for TSH during pregnancy—trimester-specific reference intervals show physiologically lower TSH values. 2

• Do not delay dose adjustment until the first prenatal visit—increase levothyroxine as soon as pregnancy is confirmed (positive home pregnancy test). 4, 5