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6/1/2016

Hyperthyroidism in Pregnancy

Author: Helen R. Dunnington, MD

Mentor: Laurie S. Swaim, MD
Editor: Eduardo Lara-Torre, MD

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Thyroid diseases in pregnancy must be differentiated from normal physiologic gestational 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 measurements, with subsequent normalization.

Hyperthyroidism occurs in approximately 0.2% of pregnancies, with Graves’ disease accounting for 95% of the 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 subspecialist referral when detected.   Most neonates born to mothers with Graves’ disease are euthyroid.  Transient hypothyroidism occurs in 10 to 20% of newborns of treated mothers. Less than 5% of neonates will be hyperthyroid due to transplacental passage of TSH receptor antibodies (TRAb’s). 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 an FDA safety alert secondary to maternal hepatotoxicity. Medication dosing is started empirically (PTU 50-150 mg/day; methimazole 10-40 mg/day) and titrated every two to four weeks to achieve desired free T4 levels. Transient leukopenia occurs in approximately 10% of pregnant women taking thioamide medications and does not require discontinuation. Medication related agranulocytosis (<1% of patients) can occur suddenly and monitoring serial blood counts is not useful. Patients should discontinue the medication during suspected acute infection episodes and have their blood counts checked.

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, and gastrointestinal and CNS dysfunction. If untreated, it may cause multiorgan decompensation. Thyrotoxic heart failure occurs in 8% of pregnancies with uncontrolled hyperthyroidism. Treatment 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 when possible during thyroid storm as fetal status may improve with maternal stabilization.

Further Reading:

American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. Thyroid Disease in Pregnancy: ACOG Practice Bulletin, Number 223. Obstet Gynecol. 2020;135(6):e261-e274. doi:10.1097/AOG.0000000000003893

Initial Approval March 2015; Revised September 2017. Reaffirmed March 2019; Revised September 2020

 

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