Management of Elevated TSI in Pregnant Patients with Graves' Disease History
Pregnant patients with a history of Graves' disease and elevated thyroid-stimulating immunoglobulins (TSI) require close monitoring with measurement of TSI levels in early third trimester, and if TSI exceeds 2.5-3 times normal, fetal surveillance with ultrasound is mandatory to detect fetal thyrotoxicosis, even in women who have undergone thyroid ablation or thyroidectomy. 1, 2, 3
Risk Stratification Based on TSI Levels
The critical threshold for predicting fetal and neonatal thyrotoxicosis is TSI levels measured in the early third trimester:
- TSI > 70% (or >2.5-3 times normal): High risk for neonatal thyrotoxicosis, occurring in 100% of cases at this level 4, 3
- TSI 30-70%: Moderate risk requiring enhanced surveillance 4
- TSI < 30%: Lower risk for fetal hyperthyroidism but increased risk for fetal hypothyroidism if mother is on antithyroid drugs 4
Importantly, women with iatrogenic hypothyroidism on levothyroxine (post-ablation or post-thyroidectomy) have 3.3 times higher odds of neonatal thyrotoxicosis compared to those on antithyroid drugs, because TSI antibodies cross the placenta freely without the protective effect of antithyroid medications 3.
Fetal Surveillance Protocol
When maternal TSI is elevated (>2.5-3 times normal) in early third trimester, initiate fetal ultrasound surveillance looking for:
- Fetal tachycardia (heart rate persistently >160-170 bpm) 2, 5
- Fetal goiter/thyromegaly 2, 5
- Oligohydramnios 3
- Hydrops fetalis 3
- Intrauterine growth restriction 6
If ultrasound findings suggest fetal thyrotoxicosis, cordocentesis should be performed to measure fetal thyroid function directly, allowing precise adjustment of maternal antithyroid medication to treat the fetus 2, 3.
Medical Management Strategy
For Women with Active Graves' Disease on Antithyroid Drugs:
- Use propylthiouracil (PTU) during first trimester as the preferred agent because methimazole carries risk of congenital malformations 1, 7, 8
- Switch to methimazole after first trimester due to PTU's risk of severe maternal hepatotoxicity 1, 7, 8
- Target maternal free T4 in the high-normal range using the lowest possible dose to minimize fetal thyroid suppression while preventing maternal complications 1, 2, 5
- Monitor thyroid function tests every trimester and adjust dosing accordingly 1, 9
For Women with Prior Thyroid Ablation/Thyroidectomy on Levothyroxine:
This group requires heightened vigilance because they lack the protective effect of antithyroid drugs against transplacental TSI:
- Measure TSI levels in early third trimester (around 28-32 weeks) 2, 3
- If TSI > 2.5 times normal, initiate fetal ultrasound surveillance even though the mother is euthyroid on levothyroxine 2, 3
- If fetal thyrotoxicosis is confirmed, initiate maternal antithyroid drug therapy specifically to treat the fetus, adjusting maternal levothyroxine as needed to maintain maternal euthyroidism 2
Delivery and Neonatal Management
At delivery, obtain cord blood for:
Critical timing consideration: Neonatal thyrotoxicosis may not manifest immediately at birth if the mother was on antithyroid drugs, as these medications suppress fetal thyroid function. Clinical hyperthyroidism typically emerges 2-7 days after delivery as maternal antithyroid drugs clear from the neonatal circulation, while maternal TSI antibodies persist for weeks to months 2, 6.
Monitor neonates for signs of thyrotoxicosis including:
- Tachycardia 6
- Poor weight gain despite increased appetite 6
- Hyperexcitability and irritability 6
- Goiter 6
- Hepatosplenomegaly 6
- Stare and eyelid retraction 6
Maternal Complications to Monitor
Inadequately treated or untreated hyperthyroidism increases maternal risk for:
- Severe preeclampsia 10, 1
- Preterm delivery 10, 1
- Heart failure 10, 8
- Miscarriage 10, 5
- Thyroid storm (medical emergency) 10, 1
Key Pitfalls to Avoid
Do not assume that women with prior thyroid ablation are at low risk - they may have the highest risk for neonatal thyrotoxicosis if TSI remains elevated, because the fetus receives stimulating antibodies without the protective effect of antithyroid drugs 3.
Do not use total T4/T3 levels for monitoring - pregnancy increases thyroxine-binding globulin, making total hormone levels unreliable; always use free T4 or free thyroxine index 9, 5.
Do not continue PTU beyond first trimester unless methimazole is contraindicated, due to severe hepatotoxicity risk 1, 7, 8.
Do not delay fetal assessment when TSI is markedly elevated - waiting for obvious clinical signs may result in severe fetal thyrotoxicosis with permanent sequelae 2, 3.