TRH Levels in Normal Pregnancy
Thyrotropin-releasing hormone (TRH) does NOT increase during normal pregnancy; the observed hormonal changes are driven by placental CRH and hCG, not by TRH elevation. 1
Distinction Between CRH and TRH in Pregnancy
The placenta synthesizes corticotropin-releasing hormone (CRH) in addition to the hypothalamus, causing CRH concentrations to increase exponentially throughout pregnancy and to reach levels that, in non-pregnant individuals, are seen only under extreme stress conditions 1. This is fundamentally different from TRH physiology.
- Unlike CRH, TRH does not increase during pregnancy 1
- The observed hormonal changes during gestation are driven by placental CRH and human chorionic gonadotropin (hCG), not by TRH elevation 1
Evidence on TRH in Pregnancy
While one older study from 1981 reported significantly higher plasma TRH levels in the second trimester compared to non-pregnant controls 2, this finding has not been consistently replicated and does not represent the current understanding of thyroid regulation in pregnancy.
- The primary thyroid stimulator in early pregnancy is hCG, which acts as a weak thyroid stimulator and causes modest elevation in free thyroid hormone levels 3
- This hCG-mediated increase in thyroid hormones leads to a modest reduction in pituitary TSH secretion, particularly at 9-12 weeks of gestation 3
- Bioassayable thyroid-stimulating activity correlates with hCG levels (P < 0.01), not with TRH 3
Thyroid Hormone Changes in Pregnancy
The key physiological changes in pregnancy involve:
- Total T4 and T3 concentrations increase significantly due to elevated thyroid-binding globulin (TBG) 2, 4
- Free T4 (by dialysis) becomes elevated after 10 weeks of pregnancy 3
- Free T3 concentration rises at 13-20 weeks of gestation 3
- TSH levels are physiologically lower than in the non-pregnant population, particularly at 9-12 weeks 4, 3
Clinical Implications
For clinical practice, recognize that:
- TSH in pregnancy is physiologically lower than in non-pregnant women, and trimester-specific reference intervals should be used 4
- The TRH test remains valid during pregnancy for assessing thyroid function 5
- Maternal TRH administration can cross the placenta and stimulate the fetal pituitary, but this is a pharmacological effect, not a physiological one 6
Common Pitfalls
- Do not confuse elevated total thyroid hormones (due to increased TBG) with true hyperthyroidism 5
- Do not assume TRH drives the thyroid changes in pregnancy—the mechanism is primarily hCG-mediated thyroid stimulation in early pregnancy 1, 3
- Avoid using non-pregnant reference ranges for TSH in pregnant women, as this will lead to overdiagnosis of hypothyroidism 4