1. Describe the normal physiologic changes in thyroid function during pregnancy.

Test Pregnancy Change
 Thyroid-stimulating hormone (TSH) None
 Thyroid-binding globulin (TBG) Increases
 Total thyroxine (T4) Increases
 Total tri-iodothyronine (T3) Increases
 T3 total resin uptake (T3RU) Decreases
 Free T4 None
 Free T3 None

2. Explain the increase in T4 and T3 seen during normal pregnancy.

Approximately 70% of circulating T4 and T3 is bound to TBG. Pregnancy results in an estrogen-mediated increase in TBG and hence increased T4 and T3. However, the free thyroid hormone levels remain unchanged.

3. List the indications for thyroid function testing during pregnancy.

The most common indications for ordering a thyroid panel are: women on thyroid hormone, family history of autoimmune thyroiditis, presence of goiter, past history of radiation to thyroid, and type 1 diabetes.

4. What is the incidence of hyperthyroidism in pregnancy? What are the most common causes?

Hyperthyroidism affects 1:2000 pregnancies. Causes of hyperthyroidism in pregnancy include Graves’ disease, toxic adenoma, subacute thyroiditis, iatrogenic ingestion of thyroxine, transient hyperthyroidism secondary to hyperemesis gravidarum, and gestational trophoblastic disease.

5. What is Graves’ disease? How does it affect the mother, fetus, and newborn infant?

Graves’ disease results in maternal hyperthyroidism secondary to autoantibodies capable of stimulating thyroxine synthesis. Maternal symptoms include weight loss or poor weight gain, tachycardia, and heat intolerance. Laboratory studies reveal increased T4 and T3 levels, an increased free thyroid index, and a low TSH. Untreated maternal hyperthyroidism results in an increased risk of preeclampsia and congestive heart failure.

The thyroid-stimulating antibodies can cross the placenta readily to stimulate the fetal thyroid. Fetal complications include in utero demise, prematurity, intrauterine growth retardation, a widespread fetal autoimmune reaction with lymphatic hypertrophy and thrombocytopenia, fetal goiter, and fetal exophthalmos.

Affected newborns can be expected to have a transient course over 1-5 months as the maternal autoantibodies are slowly cleared from their systems.

6. Should diagnostic iodine studies be performed to confirm the diagnosis of Graves’ disease during pregnancy?

No. Such iodine studies are performed with radioactive tagging. Radioactive iodine crosses the placenta and is concentrated in the fetal thyroid after 10 weeks’ gestation. Iatrogenic fetal hypothyroidism can result.

7. What are the treatment options for Graves’ disease during pregnancy?

Propylthiouracil (PTU) is the treatment of choice. It generally decreases both T4 and the symptoms by 4 weeks after initiating therapy. PTU is gradually decreased thereafter to maintain the mother’s T4 at upper limits of normal and to prevent overtreatment and hypothyroidism. Some advocate continuing to decrease PTU and even discontinuing it during the third trimester. Some women experience temporary remission of disease possibly secondary to the relative immunosuppression of pregnancy.

Methimazole is an alternative treatment. It is not the first-line drug due to reports of scalp defects (aplasia cutis) in newborns exposed to methimazole. Beta blockers such as propranolol may diminish the symptoms of thyrotoxicosis. Failure of medical therapy to alleviate the symptoms may necessitate a subtotal thyroidectomy.

Radioactive iodine therapy for gland ablation is contraindicated for the same reasons that diagnostic studies with radioactive iodine should not knowingly be undertaken.

8. Describe the fetal effects of therapy with PTU.

PTU crosses the placenta and iatrogenic fetal hypothyroidism can be produced, with the long-term effects not clearly established. There is some evidence for delayed bone age and central nervous system effects in exposed infants.

9. How can an infant still develop neonatal Graves’ disease when the mother’s hyperthyroidism is well controlled with PTU?

Transplacental passage of thyroid-stimulating antibodies can result in neonatal Grave’s disease. These antibodies remain in the maternal circulation regardless of the treatment of the mother. Even mothers with hypothyroidism secondary to subtotal thyroidectomy or radiation therapy for Graves’ disease are at risk for a fetus with thyrotoxicosis. Neonatal Graves’ disease occurs in about 1% of women with Graves’ disease regardless of their history of treatment. Treatment of the mother who has had a subtotal thyroidectomy and is on thyroid replacement therapy may be necessary and require PTU for the sole purpose of treating fetal hyperthyroidism caused by autoantibodies.

Key points: thyroid disease in pregnancy

  • Circulating T4 and T3 increase in pregnancy secondary to increased thyroid-binding globulin, but free levels are unchanged.
  • Even with well-controlled hyperthyroidism in the mother, thyroid-stimulating antibodies can cross the placenta and cause fetal or neonatal hyperthyroidism.
  • PTU is the first-line treatment for hyperthyroidism because methimazole is associated with a risk of aplasia cutis.
  • Untreated maternal hypothyroidism is associated with maternal and fetal complications.

10. How does pregnancy affect Graves’ disease?

Patients tend to have aggravation of symptoms during the first half, followed by amelioration during the second half of pregnancy and postpartum recurrence. This is thought to be due to the relative immunosuppression of pregnancy.

11. Can women on PTU breastfeed?

Yes. PTU is excreted in small quantities in breast milk and can theoretically suppress the infant’s thyroid function. However, because the amount excreted is small, breastfeeding is generally permitted in conjunction with monitoring of the newborn’s thyroid function.

12. What is “thyroid storm”? When does it usually present?

Thyroid storm is characterized by a hypermetabolic state, fever, and change in mental status. This life-threatening complication can occur during labor or cesarean section, or in conjunction with an antepartum or postpartum infection. Thyroid storm can also occur in patients with gestational trophoblastic disease. Most often it manifests itself in the woman with unrecognized hyperthyroidism.

13. How is thyroid storm managed?

By symptomatic and supportive treatment of the pyrexia, tachycardia, and severe dehydration. Thionamides, PTU, beta-blocking agents, steroids, iodines, or ipodate (to block thyroid hormone release) are the mainstays of therapy. It is important to treat any associated hypertension, infection, or anemia.

14. What are the common causes of maternal hypothyroidism?

Common etiologies include: Hashimoto’s thyroiditis, previous treatment of Graves’ disease by radioactive iodine or subtotal thyroidectomy, and excessive doses of PTU for the treatment of Graves’ symptomatology.

15. What are the maternal, fetal, and newborn effects of untreated hypothyroidism?

Most women with untreated hypothyroidism are subfertile, since marked hypothyroidism usually results in increased prolactin levels (secondary to increased thyrotropin-releasing hormone) and anovulation. In women with overt hypothyroidism who do become pregnant, there is a significantly higher incidence of anemia, preeclampsia, abruption, postpartum hemorrhage, and cardiac dysfunction. Likewise, fetal complications, including low birth weight and perinatal demise, are increased. Lesser degrees of untreated hypothyroidism may be associated with pregnancy loss and prolonged gestation. Women with subclinical disease (increased TSH but normal T4) and women receiving adequate replacement therapy have better outcomes.

16. How should the hypothyroid mother be treated?

Treatment consists of 1.6 μg/kg of levothyroxine (Synthroid, Levothroid, or Levoxyl), with variation on an individual basis. Assessment of TSH in the first trimester seems reasonable, because up to 45% of treated women with hypothyroidism require higher doses during pregnancy. Postpartum, preconception doses are appropriate, with assessment of TSH 6-12 weeks after delivery.

17. Should women with hyperemesis gravidarum have thyroid function tests?

Hyperemesis gravidarum in the presence of a viable gestation has been associated with abnormal values on thyroid studies. It is thought that elevated hCG seen in these patients has TSH-like effects. The majority of these women have no other clinical signs of hyperthyroidism, and treatment is not advocated. In a small number of cases, hyperthyroidism exists clinically, and treatment of thyrotoxicosis can help to alleviate hyperemesis gravidarum. Use of free T4 by equilibrium dialysis may help to clarify thyroid status.

18. What is postpartum thyroiditis?

Occurring 1-8 months postpartum, this condition may affect 5% of parturients. Initial hyperthyroidism (1-4 months) is followed by hypothyroidism (5-8 months), with thyroid antibodies often present. Spontaneous recovery occurs, but during the intervening period may be misdiagnosed as postpartum depression or psychosis. In 10-30% hypothyroidism is permanent. Postpartum thyroiditis tends to recur with subsequent pregnancies.

19. What diagnostic tests would you order for a woman with a thyroid nodule during pregnancy?

An ultrasound exam can disclose if the nodule is cystic or solid. Solid nodules are more likely to be malignant. Confirmation is by fine-needle aspiration or tissue biopsy. Avoid radioactive iodine, especially in the first trimester.

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