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Hyperthyroidism in Pregnancy

6/1/2016 - Helen R. Dunnington, MD

Mentor: Laurie S. Swaim, MD

Editor:  Pamela D. Berens, MD

Approved:  3/1/16

Thyroid diseases in pregnancy must be differentiated from normal physiologic adaptations including increased thyroid volume (up to 30%) and a 40-100% increase in thyroid hormone production. Cross reactivity between human chorionic gonadotropin and thyroid stimulating hormone (TSH) during the first trimester frequently results in elevated free thyroxine (FT4) and decreased TSH with subsequent normalization.

Graves’ disease occurs in approximately 1% of pregnancies, accounting for 95% of hyperthyroidism cases. Possible symptoms include nervousness, palpitations, frequent stools, diaphoresis, heat intolerance, weight loss, and insomnia. Physical exam findings may include goiter, tachycardia, hypertension, tremors, ophthalmopathy (lid lag and retraction) and pretibial edema. Laboratory findings include decreased TSH and increased free T4. Detection of thyrotropin receptor antibodies is confirmatory and may be warranted in certain circumstances.  Radionuclide studies are contraindicated in pregnancy.

Pregnancy outcomes are related to free T4 level, with a therapeutic goal to reduce FT4 to at or slightly above the upper limit of normal. Uncontrolled maternal hyperthyroidism is associated with an increased risk of preeclampsia, heart failure, and first trimester miscarriage. Postpartum exacerbation or relapse of Grave’s disease is not unusual.

Potential fetal effects include preterm birth, growth restriction, goiter, tachycardia, hydrops, and stillbirth. Ultrasound to evaluate fetal growth is warranted. Other findings including tachycardia, goiter, and hydrops prompt further investigation.  Fetal thyrotoxicosis is rare but warrants experienced management when detected.   Most neonates born to mothers with Graves’ disease are euthyroid.  Transient hypothyroidism occurs in 10 to 20% of newborns of treated mothers and < 5% of neonates will be hyperthyroid due to transplacental antibody passage. Neonatal Graves’ disease is not accurately predicted by maternal thyroid levels at delivery.   

Overt hyperthyroidism in pregnancy is treated with propylthiouracil (PTU) during the first trimester and methimazole subsequently to limit potential medication associated risks. First trimester methimazole use is associated with a rare embryopathy characterized by esophageal or choanal atresia and aplasia cutis. While PTU crosses the placenta less readily than methimazole, PTU carries a FDA safety alert secondary to maternal hepatotoxicity. Transient leukopenia occurs in approximately 10% of pregnant women taking thioamide medications and does not require discontinuation. Medication should be discontinued with symptoms of maternal infection due to risk of agranulocytosis (<1% of patients).  Medication dosing is started empirically and titrated every two to four weeks to achieve desired free T4 levels.

Thyroid storm and thyrotoxic heart failure are rare life threatening conditions. Thyroid storm occurs in 1-2% of hyperthyroid pregnancies and presents with abrupt onset of fever, tachycardia, cardiac arrhythmia, gastrointestinal and CNS dysfunction. If untreated, it may cause multiorgan decompensation. Thyrotoxic heart failure occurs in 8% of pregnancies with uncontrolled hyperthyroidism. Treatment for these sequelae requires an intensive care setting. Immediate therapeutic goals are inhibiting release of triiodothyronine (T3) and T4 with PTU and iodine, and blocking peripheral conversion of T4 to T3 with corticosteroids. Beta blockers may control tachycardia, but potential effects on heart failure should be considered. The underlying cause of hyperthyroidism requires treatment. Delivery should be avoided during thyroid storm as fetal status may improve with maternal stabilization.

Further Reading:

Thyroid disease in pregnancy. Practice Bulletin No. 148. American College of Obstetricians and Gynecologists. Obstet Gynecol 2015; 125:996–1005.

Kenyon AP, Nelson-Piercy C. Thyroid Disease.  In: James, Steer, Weiner, and Gonik, eds. High-Risk Pregnancy, 4th ed.  Chapter 45, 813-825.e2. Elsevier Inc., 2011.

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