Low TSH with Normal Free T3 and Free T4 in Second Trimester
In a second-trimester pregnant woman with low TSH but normal free T3 and free T4, this most commonly represents physiologic gestational thyrotoxicosis driven by elevated hCG and requires no treatment—simply monitor thyroid function every 2–4 weeks to confirm spontaneous resolution. 1
Understanding the Physiology
Human chorionic gonadotropin (hCG) peaks in late first trimester and remains elevated through the second trimester, causing transient TSH suppression because hCG has weak thyroid-stimulating activity that directly stimulates the thyroid gland. 2
This physiologic suppression of TSH is normal in pregnancy—median first-trimester TSH (1.05 mIU/L) is lower than second-trimester TSH (1.23 mIU/L), and both are lower than non-pregnant values. 3
Free T4 and free T3 gradually decline as pregnancy progresses, with free T4 highest in early pregnancy and slightly depressed by the third trimester while remaining within normal range. 4
Diagnostic Algorithm
Step 1: Confirm Normal Free T3 and Free T4
Measure both free T4 and free T3 using trimester-specific reference intervals—non-pregnant reference ranges will misclassify thyroid status in pregnancy. 2, 5
If free T4 and free T3 are both normal for gestational age, this confirms isolated biochemical hyperthyroidism (suppressed TSH with normal thyroid hormones). 1
Step 2: Assess for Hyperemesis Gravidarum
Ask specifically about nausea, vomiting, weight loss, and dehydration—hyperemesis gravidarum with biochemical hyperthyroidism is a transient gestational thyrotoxicosis that resolves spontaneously with treatment of vomiting. 1
If hyperemesis is present, antithyroid drugs are NOT recommended because the condition resolves on its own as hCG levels decline and vomiting improves. 1
Step 3: Rule Out Graves' Disease
Check for overt hyperthyroid symptoms: tachycardia disproportionate to dehydration, tremor, heat intolerance, anxiety, or goiter. 1
If these symptoms are present, measure thyroid-stimulating immunoglobulin (TSI) or TSH receptor antibodies to distinguish Graves' disease from gestational thyrotoxicosis. 1, 6
Graves' disease requires treatment with propylthiouracil (PTU) in the first trimester, then switch to methimazole for the second and third trimesters. 6
Management of Isolated Low TSH with Normal Free T3/T4
No Antithyroid Medication
- Do NOT start propylthiouracil or methimazole when TSH is suppressed but free T4 and free T3 are normal and the patient is asymptomatic—this represents physiologic adaptation, not pathologic hyperthyroidism. 1
No Beta-Blocker Unless Symptomatic
- Propranolol or other beta-blockers should be used ONLY when overt hyperthyroid symptoms develop (e.g., tachycardia, tremor, heat intolerance, anxiety)—they are unnecessary in asymptomatic patients with purely biochemical abnormalities. 1
Monitor Thyroid Function
Re-measure TSH and free T4 every 2–4 weeks to confirm spontaneous resolution of the biochemical abnormalities as hCG levels decline. 1
TSH typically normalizes within several weeks as hCG levels decline and vomiting improves in hyperemesis gravidarum. 1
Check Hepatic Enzymes if Hyperemesis Present
- Elevated AST/ALT occurs in 59% of pregnant women with hyperthyroid biochemistry plus hyperemesis (versus 18% in euthyroid women with hyperemesis), and typically normalizes with hydration and symptom resolution. 1
Fetal Monitoring
Monitor fetal heart rate and growth—routine ultrasound screening for fetal goiter is NOT required unless clinical concerns arise. 1
Transient fetal or neonatal thyroid suppression may occur but rarely necessitates treatment—inform the newborn's care team about maternal thyroid status. 6
Expected Clinical Course
With adequate supportive care (hydration, anti-emetics, thiamine if hyperemesis present), hyperemesis gravidarum usually improves within 1–2 weeks. 1
Biochemical hyperthyroidism typically resolves within several weeks as hCG levels decline and vomiting improves. 1
When hyperemesis is appropriately managed, major maternal or fetal adverse outcomes are uncommon—however, severe disease is associated with increased risk of low birth weight and preterm delivery. 1
Critical Pitfalls to Avoid
Do NOT treat isolated biochemical hyperthyroidism (low TSH with normal free T3/T4) with antithyroid drugs—this represents physiologic gestational thyrotoxicosis, not Graves' disease. 1
Do NOT use non-pregnant reference ranges for TSH, free T4, or free T3—pregnancy-specific reference intervals are essential to avoid misclassification. 2, 5
Do NOT assume Graves' disease without checking TSI or TSH receptor antibodies—gestational thyrotoxicosis is far more common in the second trimester. 1, 6
Do NOT start beta-blockers for asymptomatic biochemical abnormalities—reserve propranolol for patients with overt hyperthyroid symptoms. 1