The American College of Physicians’ Guideline Grading System

Figure 1. Testing For Thyroid Dysfunction In Pregnancy

Screening for Thyroid Dysfunction Before or During Pregnancy

• All pregnant women should be verbally screened at the initial prenatal visit for any history of thyroid dysfunction, and prior or current use of either thyroid hormone (LT4) or anti-thyroid medications (methimazole [MMI], carbimazole [CM], or propylthiouracil [PTU]). (S-H)
• Universal screening to detect low free thyroxine concentrations in pregnant women is NOT recommended. (W-M)
• All patients seeking pregnancy, or newly pregnant, should undergo clinical evaluation. If any of the following risk factors are identified, testing for serum TSH is recommended. (S-M)
  1. A history of hypothyroidism/hyperthyroidism or current symptoms/signs of thyroid dysfunction
  2. Known thyroid antibody positivity or presence of a goiter
  3. History of head or neck radiation or prior thyroid surgery
  4. Age >30 years
  5. Type 1 diabetes or other autoimmune disorders
  6. History of pregnancy loss, preterm delivery, or infertility
  7. Multiple prior pregnancies (≥2)
  8. Family history of autoimmune thyroid disease or thyroid dysfunction
  9. Morbid obesity (BMI ≥40 kg/m²)
  10. Use of amiodarone or lithium, or recent administration of iodinated radiologic contrast
  11. Residing in an area of known moderate to severe iodine insufficiency
• There is insufficient evidence to recommend for or against universal screening for abnormal TSH concentrations in early pregnancy. (I)
• There is insufficient evidence to recommend for or against universal screening for abnormal TSH concentrations preconception, with the exception of women planning assisted reproduction or those known to have positive TPOAb. (I)

Thyroid Function Testing and Pregnancy

• When possible, population-based trimester-specific reference ranges for serum thyroid-stimulating hormone (TSH) should be defined through assessment of local population data representative of a healthcare provider’s practice. Reference range determinations should only include pregnant women with no known thyroid disease, optimal iodine intake, and negative autoantibodies to thyroid peroxidase (TPOAb) status. (S-M)
• The accuracy of serum Free T4 measurement by the indirect analog immunoassays is influenced by pregnancy and also varies significantly by manufacturer. If measured in pregnant women, assay method-specific and trimester-specific pregnancy reference ranges should be applied. (S-M)
• In lieu of measuring free T4, total T4 measurement (with a pregnancy-adjusted reference range), is a highly reliable means of estimating hormone concentration during the last part of pregnancy. Accurate estimation of the free T4 concentrations can also be done by calculating a free thyroxine index. (S-M)
  • A total T4 upper range determination can be calculated by shifting the nonpregnant limit 50% higher. However, this can only be used after week 16 of pregnancy. If a T4 measurement is required before that time (i.e. weeks 7–16 of pregnancy), a calculation can be made for the upper reference range based on increasing the non-pregnant upper reference limit by 5% per week, beginning with week 7. For example, at 11 weeks of gestation (4 weeks beyond week 7), the upper reference range for T4 is increased by 20% (four weeks × 5%/week)

Iodine Status and Nutrition

• Median urinary iodine concentrations can be used to assess the iodine status of populations, but single spot or 24-hour urine iodine concentrations are NOT valid markers for the iodine nutritional status of individual patients. (S-H)
• All pregnant women should ingest approximately 250 μg iodine daily. To achieve a total of 250 μg iodine ingestion daily, strategies may need to be varied based on country of origin. (S-H)
• In most regions, including the United States, women who are planning pregnancy or currently pregnant should supplement their diet with a daily oral supplement that contains 150 μg of iodine in the form of potassium iodide. This is optimally started 3 months in advance of planned pregnancy. (S-M)
• In low-resource countries and regions where neither salt iodization nor daily iodine supplements are feasible, a single annual dose of ~400 mg iodized oil for pregnant women and women of childbearing age can be used as a temporary measure to protect vulnerable populations. This should NOT be employed as a long-term strategy or in regions where other options are available. (W-M).
• There is no need to initiate iodine supplementation in pregnant women who are being treated for hyperthyroidism or who are taking levothyroxine (LT4). (W-L)
• Excessive doses of iodine exposure during pregnancy should be avoided except in preparation for the surgical treatment of Graves' disease. Clinicians should carefully weigh the risks and benefits when ordering medications or diagnostic tests that will result in high iodine exposure. (S-M)
• Sustained iodine intake from diet and dietary supplements exceeding 500 μg daily should be avoided during pregnancy due to concerns about the potential for fetal thyroid dysfunction. (S-M)

Thyroid Auto-Antibodies & Pregnancy Complications

• Euthyroid, but thyroid peroxidase (TPO) or thyroglobulin (Tg) antibody positive, pregnant women should have measurement of serum TSH concentration performed at time of pregnancy confirmation, and every 4 weeks through mid-pregnancy. (S-H)
• Selenium supplementation is NOT recommended for the treatment of TPOAb-positive women during pregnancy. (W-M)
• Intravenous immunoglobulin treatment of euthyroid women with a history of recurrent pregnancy loss is NOT recommended. (W-L)
• There is insufficient evidence to conclusively determine whether LT4 therapy decreases pregnancy loss risk in TPOAb-positive, euthyroid women who are newly pregnant. However, administration of LT4 to TPOAb-positive, euthyroid pregnant women with a prior history of loss may be considered given its potential benefits in comparison to its minimal risk. In such cases, 25–50 mcg of LT4 is a typical starting dose. (W-L)
• There is insufficient evidence to recommend for or against treating euthyroid, thyroid autoantibody positive pregnant women with LT4 to prevent preterm delivery. (I)

The Impact of Thyroid Illness upon Infertility and Assisted Reproduction

• Evaluation of serum TSH concentration is recommended for all women seeking care for infertility. (W-M)
• LT4 treatment is recommended for infertile women with overt hypothyroidism who desire pregnancy. (S-M)
• There is insufficient evidence to determine if LT4 therapy improves fertility in subclinically hypothyroid, thyroid auto-antibody negative women who are attempting natural conception (not undergoing antiretroviral therapy [ART]). However, administration of LT4 may be considered in this setting given its ability to prevent progression to more significant hypothyroidism once pregnancy is achieved. Furthermore, low dose LT4 therapy (25–50 mcg daily) carries minimal risk. (W-L)
• There is insufficient evidence to determine if LT4 therapy improves fertility in nonpregnant, euthyroid, thyroid autoantibody positive women who are attempting natural conception (not undergoing ART). Therefore, no recommendation can be made for LT4 therapy in this setting. (I)
• Subclinically hypothyroid women undergoing in vitro fertilization or intracytoplasmic sperm injection should be treated with LT4. The goal of treatment is to achieve a TSH concentration <2.5 mU/L. (S-M)
• There is insufficient evidence to determine whether LT4 therapy improves the success of pregnancy following ART in TPOAb-positive, euthyroid women. However, administration of LT4 to TPOAb-positive, euthyroid women undergoing ART may be considered given its potential benefits in comparison to its minimal risk. In such cases, 25–50 mcg of LT4 is a typical starting dose. (W-L)
• Glucocorticoid therapy is NOT recommended for euthyroid, thyroid auto-antibody positive women undergoing ART. (W-M)
• When possible, thyroid function testing should be performed either before or 1–2 weeks after controlled ovarian hyperstimulation, since results obtained during the course of controlled ovarian stimulation may be difficult to interpret. (W-M)
• In women who achieve pregnancy following controlled ovarian hyperstimulation, TSH elevations should be treated according to the recommendations outlined under Hypothyroidism and Pregnancy. In non-pregnant women with mild TSH elevations following controlled ovarian stimulation, serum TSH measurements should be repeated in 2–4 weeks, since levels may normalize. (W-M)