Definitions for the strength of recommendations (A-D,I) are presented at the end of the "Major Recommendations" field. The strength of each recommendation was graded according to the United States Preventive Services Task Force (USPSTF).
Thyroid Function Tests in Pregnancy
R1. Trimester-specific reference ranges for thyrotropin (TSH), as defined in populations with optimal iodine intake, should be applied. Level B-USPSTF
R2. If trimester-specific reference ranges for TSH are not available in the laboratory, the following reference ranges are recommended: first trimester, 0.1–2.5 mIU/L; second trimester, 0.2–3.0 mIU/L; third trimester, 0.3–3.0 mIU/L. Level I-USPSTF
R3. The optimal method to assess serum free thyroxine (FT4) during pregnancy is measurement of thyroxine (T4) in the dialysate or ultrafiltrate of serum samples employing on-line extraction/liquid chromatography/tandem mass spectrometry (LC/MS/MS). Level A-USPSTF
R4. If FT4 measurement by LC/MS/MS is not available, clinicians should use whichever measure or estimate of FT4 is available in their laboratory, being aware of the limitations of each method. Serum TSH is a more accurate indication of thyroid status in pregnancy than any of these alternative methods. Level A-USPSTF
R5. In view of the wide variation in the results of FT4 assays, method-specific and trimester-specific reference ranges of serum FT4 are required. Level B-USPSTF
Hypothyroidism in Pregnancy
R6. Overt hypothyroidism (OH) should be treated in pregnancy. This includes women with a TSH concentration above the trimester-specific reference interval with a decreased FT4, and all women with a TSH concentration above 10.0 mIU/L irrespective of the level of FT4. Level A-USPSTF
R7. Isolated hypothyroxinemia should not be treated in pregnancy. Level C-USPSTF
R8. Subclinical hypothyroidism (SCH) has been associated with adverse maternal and fetal outcomes. However, due to the lack of randomized controlled trials there is insufficient evidence to recommend for or against universal levothyroxine (LT4) treatment in thyroglobulin antibody-negative (TAb-) pregnant women with SCH. Level I-USPSTF
R9. Women who are positive for thyroid peroxidase antibody (TPOAb) and have SCH should be treated with LT4. Level B-USPSTF (Dissent from one committee member: There is no consistent prospective evidence demonstrating that women who are positive for thyroid peroxidase antibody (TPOAb+), but who have SCH only, achieve maternal or perinatal benefit from LT4 treatment. Correspondingly, there is no indication to treat women who are TPOAb+ and have SCH with LT4.)
R10. The recommended treatment of maternal hypothyroidism is with administration of oral LT4. It is strongly recommended not to use other thyroid preparations such as T3 or desiccated thyroid. Level A-USPSTF
R11. The goal of LT4 treatment is to normalize maternal serum TSH values within the trimester-specific pregnancy reference range (first trimester, 0.1–2.5 mIU/L, second trimester, 0.2–3.0 mIU/L, third trimester, 0.3–3.0 mIU/L). Level A-USPSTF
R12. Women with SCH in pregnancy who are not initially treated should be monitored for progression to OH with a serum TSH and FT4 approximately every 4 weeks until 16—20 weeks gestation and at least once between 26 and 32 weeks gestation. This approach has not been prospectively studied. Level I-USPSTF
R13. Treated hypothyroid patients (receiving LT4), who are newly pregnant should independently increase their dose of LT4 by approximately 25%–30% upon a missed menstrual cycle or positive home pregnancy test and notify their caregiver promptly. One means of accomplishing this adjustment is to increase LT4 from once daily dosing to a total of nine doses per week (29% increase). Level B-USPSTF
R14. There exists great inter-individual variability regarding the increased amount of T4 (or LT4) necessary to maintain a normal TSH throughout pregnancy, with some women requiring only 10%–20% increased dosing, while others may require as much as an 80% increase. The etiology of maternal hypothyroidism, as well as the preconception level of TSH, may provide insight into the magnitude of necessary LT4 increase. Clinicians should seek this information upon assessment of the patient after pregnancy is confirmed. Level A-USPSTF
R15. Treated hypothyroid patients (receiving LT4) who are planning pregnancy should have their dose adjusted by their provider in order to optimize serum TSH values to <2.5 mIU/L preconception. Lower preconception TSH values (within the nonpregnant reference range) reduce the risk of TSH elevation during the first trimester. Level B-USPSTF
R16. In pregnant patients with treated hypothyroidism, maternal serum TSH should be monitored approximately every 4 weeks during the first half of pregnancy because further LT4 dose adjustments are often required. Level B-USPSTF
R17. In pregnant patients with treated hypothyroidism, maternal TSH should be checked at least once between 26 and 32 weeks gestation. Level I-USPSTF
R18. Following delivery, LT4 should be reduced to the patient's preconception dose. Additional TSH testing should be performed at approximately 6 weeks postpartum. Level B-USPSTF
R19. In the care of women with adequately treated Hashimoto's thyroiditis, no other maternal or fetal thyroid testing is recommended beyond measurement of maternal thyroid function (such as serial fetal ultrasounds, antenatal testing, and/or umbilical blood sampling) unless for other pregnancy circumstances. Level A-USPSTF
R20. Euthyroid women (not receiving LT4) who are TAb+ require monitoring for hypothyroidism during pregnancy. Serum TSH should be evaluated every 4 weeks during the first half of pregnancy and at least once between 26 and 32 weeks gestation. Level B-USPSTF
R21. A single randomized control trial (RCT) has demonstrated a reduction in postpartum thyroiditis from selenium therapy. No subsequent trials have confirmed or refuted these findings. At present, selenium supplementation is not recommended for TPOAb+ women during pregnancy. Level C-USPSTF
Thyrotoxicosis in Pregnancy
R22. In the presence of a suppressed serum TSH in the first trimester (TSH <0.1 mIU/L), a history and physical examination are indicated. FT4 measurements should be obtained in all patients. Measurement of serum total T3 (TT3) and thyrotropin receptor antibodies (TRAb) may be helpful in establishing a diagnosis of hyperthyroidism. Level B-USPSTF
R23. There is not enough evidence to recommend for or against the use of thyroid ultrasound in differentiating the cause of hyperthyroidism in pregnancy. Level I-USPSTF
R24. Radioactive iodine (RAI) scanning or radioiodine uptake determination should not be performed in pregnancy. Level D-USPSTF
R25. The appropriate management of women with gestational hyperthyroidism and hyperemesis gravidarum includes supportive therapy, management of dehydration, and hospitalization if needed. Level A-USPSTF
R26. Antithyroid drugs (ATDs) are not recommended for the management of gestational hyperthyroidism. Level D-USPSTF
R27. Thyrotoxic women should be rendered euthyroid before attempting pregnancy. Level A-USPSTF
R28. Propylthiouracil (PTU) is preferred for the treatment of hyperthyroidism in the first trimester. Patients on methimazole (MMI) should be switched to PTU if pregnancy is confirmed in the first trimester. Following the first trimester, consideration should be given to switching to MMI. Level I-USPSTF
R29. A combination regimen of LT4 and an ATD should not be used in pregnancy, except in the rare situation of fetal hyperthyroidism. Level D-USPSTF
R30. In women being treated with ATDs in pregnancy, FT4 and TSH should be monitored approximately every 2–6 weeks. The primary goal is a serum FT4 at or moderately above the normal reference range. Level B-USPSTF
R31. Thyroidectomy in pregnancy is rarely indicated. If required, the optimal time for thyroidectomy is in the second trimester. Level A-USPSTF
R32. If the patient has a past or present history of Graves' disease, a maternal serum determination of receptor antibodies (TRAb) should be obtained at 20–24 weeks gestation. Level B-USPSTF
R33. Fetal surveillance with serial ultrasounds should be performed in women who have uncontrolled hyperthyroidism and/or women with high TRAb levels (greater than three times the upper limit of normal). A consultation with an experienced obstetrician or maternal–fetal medicine specialist is optimal. Such monitoring may include ultrasound for heart rate, growth, amniotic fluid volume and fetal goiter. Level I-USPSTF
R34. Cordocentesis should be used in extremely rare circumstances and performed in an appropriate setting. It may occasionally be of use when fetal goiter is detected in women taking ATDs to help determine whether the fetus is hyperthyroid or hypothyroid. Level I-USPSTF
R35. MMI in doses up to 20–30mg/d is safe for lactating mothers and their infants. PTU at doses up to 300 mg/d is a second-line agent due to concerns about severe hepatotoxicity. ATDs should be administered following a feeding and in divided doses. Level A-USPSTF
Clinical Guidelines for Iodine Nutrition
R36. All pregnant and lactating women should ingest a minimum of 250 µg iodine daily. Level A-USPSTF
R37. To achieve a total of 250 µg of iodine ingestion daily in North America all women who are planning to be pregnant or are pregnant or breastfeeding should supplement their diet with a daily oral supplement that contains 150 µg of iodine. This is optimally delivered in the form of potassium iodide because kelp and other forms of seaweed do not provide a consistent delivery of daily iodide. Level B-USPSTF
R38. In areas of the world outside of North America, strategies for ensuring adequate iodine intake during preconception, pregnancy, and lactation should vary according to regional dietary patterns and availability of iodized salt. Level A-USPSTF
R39. Pharmacologic doses of iodine exposure during pregnancy should be avoided, except in preparation for thyroid surgery for Graves' disease. Clinicians should carefully weigh the risks and benefits when ordering medications or diagnostic tests that will result in high iodine exposure. Level C-USPSTF
R40. Sustained iodine intake from diet and dietary supplements exceeding 500–1100 µg daily should be avoided due to concerns about the potential for fetal hypothyroidism. Level C-USPSTF
Spontaneous Pregnancy Loss, Preterm Delivery, and Thyroid Antibodies
R41. There is insufficient evidence to recommend for or against screening all women for antithyroid antibodies in the first trimester of pregnancy. Level I-USPSTF
R42. There is insufficient evidence to recommend for or against screening for thyroid antibodies, or treating in the first trimester of pregnancy with LT4 or intravenous immunoglobulin (IVIG), in euthyroid women with sporadic or recurrent abortion, or in women undergoing in vitro fertilization (IVF). Level I-USPSTF
R43. There is insufficient evidence to recommend for or against LT4 therapy in TAb+ euthyroid women during pregnancy. Level I-USPSTF
R44. There is insufficient evidence to recommend for or against LT4 therapy in euthyroid TAb+ women undergoing assisted reproduction technologies. Level I-USPSTF
R45. There is insufficient evidence to recommend for or against screening for anti-thyroid antibodies in the first trimester of pregnancy, or treating TAb+ euthyroid women with LT4, to prevent preterm delivery. Level I-USPSTF
Thyroid Nodules and Thyroid Cancer
R46. The optimal diagnostic strategy for thyroid nodules detected during pregnancy is based on risk stratification. All women should have the following: a complete history and clinical examination, serum TSH testing, and ultrasound of the neck. Level A-USPSTF
R47. The utility of measuring calcitonin in pregnant women with thyroid nodules is unknown. Level I-USPSTF
R48. Thyroid or lymph node fine-needle aspiration (FNA) confers no additional risks to a pregnancy. Level A-USPSTF
R49. Thyroid nodules discovered during pregnancy that have suspicious ultrasound features, as delineated by the 2009 American Thyroid Association (ATA) guidelines, should be considered for FNA. In instances in which nodules are likely benign, FNA may be deferred until after delivery based on patients’ preference. Level I-USPSTF
R50. The use of radioiodine imaging and/or uptake determination or therapeutic dosing is contraindicated during pregnancy. Inadvertent use of radioiodine prior to 12 weeks of gestation does not appear to damage the fetal thyroid. Level A-USPSTF
R51. Because the prognosis of women with well-differentiated thyroid cancer identified but not treated during pregnancy is similar to that of nonpregnant patients, surgery may be generally deferred until postpartum. Level B-USPSTF
R52. The impact of pregnancy on women with medullary carcinoma is unknown. Surgery is recommended during pregnancy in the presence of a large primary tumor or extensive lymph node metastases. Level I-USPSTF
R53. Surgery for thyroid carcinoma during the second trimester of pregnancy has not been demonstrated to be associated with increased maternal or fetal risk. Level B-USPSTF
R54. Pregnant women with thyroid nodules that are read as benign on FNA cytology do not require surgery during pregnancy except in cases of rapid nodule growth and/or if severe compressive symptoms develop. Postpartum, nodules should be managed according to the 2009 ATA guidelines. Level B-USPSTF
R55. When a decision has been made to defer surgery for well-differentiated thyroid carcinoma until after delivery, neck ultrasounds should be performed during each trimester to assess for rapid tumor growth, which may indicate the need for surgery. Level I-USPSTF
R56. Surgery in women with well-differentiated thyroid carcinoma may be deferred until postpartum without adversely affecting the patient's prognosis. However, if substantial growth of the well-differentiated thyroid carcinoma occurs or the emergence of lymph node metastases prior to midgestation occurs, then surgery is recommended. Level B-USPSTF
R57. Thyroid hormone therapy may be considered in pregnant women who have deferred surgery for well-differentiated thyroid carcinoma until postpartum. The goal of LT4 therapy is a serum TSH level of 0.1–1.5 mIU/L. Level I-USPSTF
R58. Pregnant patients with an FNA sample that is suspicious for thyroid cancer do not require surgery while pregnant except in cases of rapid nodular growth and/or the appearance of lymph node metastases. Thyroid hormone therapy is not recommended. Level I-USPSTF
R59. The preconception TSH goal in women with differentiated thyroid cancer (DTC), which is determined by risk stratification, should be maintained during pregnancy. TSH should be monitored approximately every 4 weeks until 16–20 weeks of gestation and once between 26 and 32 weeks of gestation. Level B-USPSTF
R60. There is no evidence that previous exposure to radioiodine affects the outcomes of subsequent pregnancies and offspring. Pregnancy should be deferred for 6 months following RAI treatment. LT4 dosing should be stabilized following RAI treatment before pregnancy is attempted. Level B-USPSTF
R61. Ultrasound and thyroglobulin (Tg) monitoring during pregnancy in patients with a history of previously treated DTC is not required for low-risk patients with no Tg or structural evidence of disease prior to pregnancy. Level B-USPSTF
R62. Ultrasound monitoring should be performed each trimester during pregnancy in patients with previously treated DTC and who have high levels of Tg or evidence of persistent structural disease prior to pregnancy. Level B-USPSTF
Postpartum Thyroiditis
R63. Women with postpartum depression should have TSH, FT4, and TPOAb tests performed. Level B-USPSTF
R64. During the thyrotoxic phase of postpartum thyroiditis (PPT), symptomatic women may be treated with beta blockers. Propranolol at the lowest possible dose to alleviate symptoms is the treatment of choice. Therapy is typically required for a few months. Level B-USPSTF
R65. ATDs are not recommended for the treatment of the thyrotoxic phase of PPT. Level D-USPSTF
R66. Following the resolution of the thyrotoxic phase of PPT, TSH should be tested every 2 months (or if symptoms are present) until 1 year postpartum to screen for the hypothyroid phase. Level B-USPSTF
R67. Women who are symptomatic with hypothyroidism in PPT should either have their TSH level retested in 4–8 weeks or be started on LT4 (if symptoms are severe, if conception is being attempted, or if the patient desires therapy). Women who are asymptomatic with hypothyroidism in PPT should have their TSH level retested in 4–8 weeks. Level B-USPSTF
R68. Women who are hypothyroid with PPT and attempting pregnancy should be treated with LT4. Level A-USPSTF
R69. If LT4 is initiated for PPT, future discontinuation of therapy should be attempted. Tapering of treatment can be begun 6–12 months after the initiation of treatment. Tapering of LT4 should be avoided when a woman is actively attempting pregnancy, is breastfeeding, or is pregnant. Level C-USPSTF
R70. Women with a prior history of PPT should have an annual TSH test performed to evaluate for permanent hypothyroidism.
R71. Treatment of TAb+ euthyroid pregnant woman with either LT4 or iodine to prevent PPT is ineffective and is not recommended. Level D-USPSTF
Thyroid Function Screening in Pregnancy
R72. There is insufficient evidence to recommend for or against universal TSH screening at the first trimester visit. Level I-USPSTF
R73. Because no studies to date have demonstrated a benefit to treatment of isolated maternal hypothyroxinemia, universal FT4 screening of pregnant women is not recommended. Level D-USPSTF
R74. There is insufficient evidence to recommend for or against TSH testing preconception in women at high risk for hypothyroidism. Level I-USPSTF
R75. All pregnant women should be verbally screened at the initial prenatal visit for any history of thyroid dysfunction and/or use of thyroid hormone (LT4) or anti-thyroid medications (MMI, carbimazole, or PTU). Level B-USPSTF
R76. Serum TSH values should be obtained early in pregnancy in the following women at high risk for overt hypothyroidism:
- History of thyroid dysfunction or prior thyroid surgery
- Age >30 years
- Symptoms of thyroid dysfunction or the presence of goiter
- TPOAb positivity
- Type 1 diabetes or other autoimmune disorders
- History of miscarriage or preterm delivery
- History of head or neck radiation
- Family history of thyroid dysfunction
- Morbid obesity (BMI ≥40 kg/m2)
- Use of amiodarone or lithium, or recent administration of iodinated radiologic contrast
- Infertility
- Residing in an area of known moderate to severe iodine sufficiency
Level B-USPSTF
(Dissent from one committee member: There is no good evidence that improved maternal or perinatal outcomes will be obtained if the criteria for thyroid function screening were different for a pregnant than a nonpregnant population. Correspondingly, criteria for screening pregnant women should not differ from the nonpregnant population.)
Definitions:
Strength of Recommendation
The strength of each recommendation was graded according to the United States Preventive Services Task Force (USPSTF) guidelines outlined below.
Level A. The USPSTF strongly recommends that clinicians provide (the service) to eligible patients. The USPSTF found good evidence that (the service) improves important health outcomes and concludes that benefits substantially outweigh harms.
Level B. The USPSTF recommends that clinicians provide (this service) to eligible patients. The USPSTF found at least fair evidence that (the service) improves important health outcomes and concludes that benefits outweigh harms.
Level C. The USPSTF makes no recommendation for or against routine provision of (the service). The USPSTF found at least fair evidence that (the service) can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.
Level D. The USPSTF recommends against routinely providing (the service) to asymptomatic patients. The USPSTF found at least fair evidence that (the service) is ineffective or that harms outweigh benefits.
Level I. The USPSTF concludes that evidence is insufficient to recommend for or against routinely providing (the service). Evidence that (the service) is effective is lacking, or poor quality, or conflicting, and the balance of benefits and harms cannot be determined.