Thyroid Disease in Pregnancy

Background

• Thyroid conditions in pregnancy may include hypothyroidism (both overt and subclinical), isolated hypothyroxinemia, hyperthyroidism (both overt and subclinical), thyroid autoimmunity (in euthyroid patients), thyroid nodules, and thyroid cancer.
• Complications of thyroid conditions in pregnancy:
  • Overt primary hypothyroidism is associated with adverse maternal effects, including gestational hypertension, placental abruption, and postpartum hemorrhage, as well as adverse fetal/offspring effects including spontaneous abortion, stillbirth, premature birth, low birth weight, and lower offspring IQ.
  • Subclinical primary hypothyroidism may be associated with increased risk of pregnancy loss, neonatal death, placental abruption, and preterm birth.
  • Overt hyperthyroidism is associated with increased risk of preeclampsia with severe features, maternal and fetal heart failure, placental abruption, premature birth, and fetal and/or neonatal hyperthyroidism.
  • Thyroid autoimmunity may be associated with increased risk of miscarriage, recurrent miscarriage, and preterm delivery in adults with normal thyroid function.
• Recommendations for thyroid function screening in pregnant women vary.

Table 1. Recommendations for Thyroid Function Screening During Pregnancy

Evaluation

• Pregnancy is associated with physiologic changes that lead to elevated total thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) and transiently lower thyroid-stimulating hormone (TSH) (particularly in early pregnancy). As a result, evaluating for thyroid function is challenging.
  • To assess thyroid function in pregnancy, measure the TSH level, which is the most sensitive indicator of gestational thyroid status (Strong recommendation).

Table 2. Normal TSH Reference Ranges During Pregnancy From Professional Organizations

• If TSH is abnormally high or low, measure free T4 (FT4) or total T4 levels or calculate the FT4 index. Total T4 should be assessed using trimester-specific reference ranges.
• For the evaluation of a suspected thyroid nodule:
  • Perform a thyroid and neck ultrasound.
  • If a thyroid nodule is detected, the decision to perform fine needle aspiration (FNA) depends on the serum TSH level.
    • If TSH levels are suppressed and persisting beyond 16 weeks, FNA may be deferred until after pregnancy; at which time, a radionuclide scan can also be performed if the TSH remains suppressed and the patient is not breastfeeding (Strong recommendation).
    • If TSH levels are not suppressed, FNA may be recommended based on the same nodule size and patterns on the ultrasound as outside of pregnancy. Clinical assessment of cancer risk or patient preference may influence the decision to perform FNA or delay the procedure until after pregnancy (Strong recommendation).

Management

• Overt primary hypothyroidism:
  • Treat overt hypothyroidism during pregnancy (Strong recommendation).
  • Administer oral levothyroxine (Strong recommendation).
  • Counsel female adults who are treated for existing hypothyroidism to independently increase levothyroxine dose by about 20%-30% (this can be achieved by taking 2 additional tablets weekly) if a home pregnancy test is positive and to urgently notify their caregiver for prompt testing and further evaluation (Strong recommendation).
  • Consider targeting the TSH goal in the lower half of the trimester-specific reference range (or < 2.5 milliunits/L if it is not available).
  • Monitor the TSH level every 4 weeks until midgestation and at least once near 30 weeks gestation (Strong recommendation).
  • After delivery:
    • readjust levothyroxine dose to preconception dose and monitor thyroid function at about 6 weeks post partum (Strong recommendation)
    • consider discontinuing levothyroxine in certain adults who initiated levothyroxine during pregnancy, especially those with dose ≤ 50 mcg/day (Weak recommendation)
• Guidance for the management of subclinical primary hypothyroidism differs among professional organizations.

Table 3. Recommendations on Use of Thyroid Replacement Therapy in Cases of Subclinical Hypothyroidism During Pregnancy

• Central hypothyroidism:
  • In pregnant patients with central hypothyroidism, advise a 25%-50% increase in levothyroxine dose (Strong recommendation).
  • Four to six weeks after uptitration of the levothyroxine dose, measure FT4 to check the adequacy of the replacement (Strong recommendation).
  • Consider aiming for a treatment goal of FT4 in the upper quartile of normal range to reduce the risk of thyroid underreplacement in the fetus.
• Isolated hypothyroxinemia should not be routinely treated in pregnancy (Weak recommendation).
• Graves disease:
  • Thionamide antithyroid drugs (such as, methimazole or propylthiouracil) are the mainstay of treatment for overt hyperthyroidism.
  • In high-risk patients (hyperthyroid status or requiring methimazole > 5-10 mg/day or propylthiouracil > 100-200 mg/day to maintain euthyroid status):
    • Give methimazole and propylthiouracil at lowest effective dose with target serum FT4/total T4 at the upper limit or moderately above the reference range (Strong recommendation).
    • Give or continue propylthiouracil from preconception through 16 weeks gestation due to a higher risk for teratogenicity with methimazole (Strong recommendation).
    • Consider switching women who are taking methimazole to propylthiouracil as early as possible (Weak recommendation).
      • Use a dose ratio of approximately 1:20 when switching from methimazole to propylthiouracil (for example, methimazole 5 mg/day is equivalent to 100 mg/day in 2 divided doses) (Strong recommendation).
      • After 16 weeks, no recommendation can be made regarding switching from propylthiouracil to methimazole due to insufficient evidence.
  • In low-risk patients (euthyroid status taking methimazole ≤ 5-10 mg/day or propylthiouracil ≤ 100-200 mg/day):
    • Consider stopping all antithyroid medication after an assessment of disease history and other risk factors in patients who are newly pregnant (Weak recommendation).
    • After stopping medications, follow-up every 1-2 weeks with a clinical examination and maternal thyroid function testing (TSH and FT4 or total T4); this can be extended to every 2-4 weeks during the second and third trimesters if the euthyroid status is maintained (Weak recommendation).
    • Consider clinical and biochemical data at each assessment of maternal thyroid status when deciding whether or not to continue withholding antithyroid medication (Weak recommendation).
  • Block-replacement therapy that combines levothyroxine and antithyroid drugs should not be used in pregnancy except in rare cases of isolated fetal hyperthyroidism (Strong recommendation).
  • Indications for thyroidectomy in pregnancy include cases of (Strong recommendation):
    • allergies or contraindications to both propylthiouracil and methimazole
    • noncompliance with drug therapy
    • euthyroid status not achieved despite high doses of antithyroid drugs
• Gestational transient thyrotoxicosis:
  • Offer supportive care including hydration in hospitalized setting if needed (Strong recommendation).
  • Do not give antithyroid drugs (Strong recommendation).
  • Consider beta-blockers for management of symptoms (low dose, given over a limited period of time).
• Thyroid nodule:
  • If the nodule is cytologically benign, manage it with surveillance strategies used for the general population (Strong recommendation).
  • If the nodule is cytologically indeterminate and:
    • without cytologically malignant lymph nodes or other signs of metastatic disease, surgery is not routinely required during pregnancy (Strong recommendation)
    • associated with clinical suspicion of aggressive behavior, consider surgery during pregnancy (Weak recommendation)
• Thyroid cancer:
  • If differentiated thyroid cancer is diagnosed early in pregnancy, consider monitoring the thyroid with a thyroid ultrasound (Weak recommendation).
    • If there is significant growth before 24-26 weeks gestation or if cytologically malignant cervical lymph nodes are present, consider surgery during pregnancy.
    • If the disease is stable or was diagnosed in the second half of pregnancy, surgery may be deferred until after delivery.
  • If medullary carcinoma or anaplastic cancer is diagnosed, strongly consider surgery after an assessment of all clinical factors (Strong recommendation).