Thyroid Disease in Pregnancy

Summary

Thyroid disease in pregnancy, mainly hypothyroidism or Graves’ hyperthyroidism, requires careful management as untreated disease increases risks of miscarriage, preeclampsia, growth restriction, and impaired neurodevelopment. Treatment involves adjusted levothyroxine for hypothyroidism and antithyroid drugs for hyperthyroidism, with close monitoring to optimize maternal and fetal outcomes.

Introduction

Thyroid disease is common in women of childbearing age and may significantly impact both maternal and fetal outcomes. Diagnosis during pregnancy is challenging, as typical symptoms—such as fatigue, heat intolerance, constipation, palpitations, and weight changes—often overlap with physiological changes of normal pregnancy. 

Pregnancy alters thyroid physiology through plasma volume expansion, increased thyroid-binding globulin (TBG) production due to elevated estrogen, and relative iodine deficiency, making standard non-pregnant reference ranges for thyroid function tests (TFTs) inappropriate.

Maternal and Fetal Thyroid Physiology in Pregnancy

• During early pregnancy, hCG transiently suppresses TSH and increases free T4 levels in the first trimester, followed by a gradual decline in free T4 as gestation advances. 

• Measurement of free T4 is the most reliable indicator of thyroid function in pregnancy, as total T3 and T4 levels are elevated due to increased TBG.

• Fetal thyroid development begins at 11–12 weeks with T4 synthesis, and by 12–14 weeks the gland can concentrate iodine. 

• A functional hypothalamic-pituitary-thyroid axis is established by around 12 weeks. 

• Placental transfer of iodine is free, whereas TSH does not cross. Limited transfer of maternal T4 occurs, which is critical for fetal neurodevelopment in the first trimester before the fetal thyroid becomes functional. 

• Thyroid-stimulating antibodies (TRAb) can cross the placenta, potentially causing fetal thyroid dysfunction.

Hypothyroidism in Pregnancy

• Hypothyroidism affects ~1% of pregnancies. Globally, iodine deficiency is the most common cause, while Hashimoto’s thyroiditis predominates in developed regions. 

• Untreated maternal hypothyroidism is associated with:

•  Miscarriage

• Preeclampsia

• Placental abruption

• Intrauterine growth restriction (IUGR)

• Stillbirth

• Impaired neurocognitive outcomes in offspring.

• Management involves: 

• continued levothyroxine replacement, with requirements increasing by 30–50% during pregnancy. 

• The therapeutic goal is maternal biochemical euthyroidism, with TSH maintained below trimester-specific thresholds. 

• TFTs should be monitored every trimester, or more frequently if dose adjustments are required. 

• Neonatal thyroid dysfunction may also occur, with maternal iodine exposure (e.g., iodide-containing medications) being a recognized cause of neonatal goiter.

Hyperthyroidism in Pregnancy

• Hyperthyroidism occurs in <1% of pregnancies, with Graves’ disease (GD) accounting for ~95% of cases. 

• Other causes include toxic adenoma, multinodular goiter, thyroiditis, and hCG-mediated thyrotoxicosis (e.g., in hyperemesis gravidarum or gestational trophoblastic disease). 

• Clinical features distinguishing hyperthyroidism from normal pregnancy include tremor, weight loss, ophthalmopathy, and pretibial myxedema.

• Diagnosis: 

• Interpretation requires trimester-specific TFT reference ranges: lower TSH and higher total T3/T4, with free T4 varying by gestation. 

• TRAb measurement is essential for women with GD to assess risk of fetal thyrotoxicosis. 

• Thyroid ultrasound is the imaging modality of choice; radioactive iodine scans are contraindicated.

• Management

• First-line treatment is antithyroid drugs (ATDs): propylthiouracil (PTU) during the first trimester due to lower teratogenicity, and methimazole/carbimazole thereafter due to hepatotoxicity risk with prolonged PTU use. 

• Postpartum, ATD doses usually need readjustment to prevent relapse.

• The aim is to maintain maternal free T4 in the upper normal range, using the lowest effective dose to minimize fetal hypothyroidism or goiter. 

• Beta-blockers may be used short-term for symptom control. 

• Radioactive iodine is contraindicated.

• Thyroidectomy may be considered in the second trimester for refractory disease or suspicion of malignancy.

• Uncontrolled hyperthyroidism increases the risk of:

• Miscarriage, preterm birth, preeclampsia, and fetal growth restriction. 

• Women require close TFT monitoring every 2–6 weeks. 

• TRAb-positive women should undergo serial ultrasound surveillance for fetal thyrotoxicosis. 

Thyroid Storm

• Thyroid storm is a rare but life-threatening complication of uncontrolled thyrotoxicosis, precipitated by infection, labor, cesarean delivery, or medication noncompliance. 

• It presents with hyperthermia, severe tachycardia, diaphoresis, dehydration, and cardiovascular collapse, and may mimic severe preeclampsia (distinguished by absence of proteinuria). 

• Maternal mortality exceeds 25%.

• Management:

•  immediate initiation of PTU (to block synthesis and peripheral conversion of T4 to T3).

• High-dose corticosteroids.

• Beta-blockers (e.g., propranolol).

• Iodine to inhibit hormone release.

• Aggressive fluid resuscitation, and supportive care.