Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline (original) (raw)

Abstract

Objective:

The objective is to provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum.

Participants:

The Chair was selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society. The Chair requested participation by the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, and the American Association of Clinical Endocrinologists, and each organization appointed a member to the task force. Two members of The Endocrine Society were also asked to participate. The group worked on the guidelines for 2 yr and held two meetings. There was no corporate funding, and no members received remuneration.

Evidence:

Applicable published and peer-reviewed literature of the last two decades was reviewed, with a concentration on original investigations. The grading of evidence was done using the United States Preventive Services Task Force system and, where possible, the GRADE system.

Consensus Process:

Consensus was achieved through conference calls, two group meetings, and exchange of many drafts by E-mail. The manuscript was reviewed concurrently by the Society’s CGS, Clinical Affairs Committee, members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions were received and incorporated into the final document. Each of the societies endorsed the guidelines.

Conclusions:

Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus. Care requires coordination among several healthcare professionals. Avoiding maternal (and fetal) hypothyroidism is of major importance because of potential damage to fetal neural development, an increased incidence of miscarriage, and preterm delivery. Maternal hyperthyroidism and its treatment may be accompanied by coincident problems in fetal thyroid function. Autoimmune thyroid disease is associated with both increased rates of miscarriage, for which the appropriate medical response is uncertain at this time, and postpartum thyroiditis. Fine-needle aspiration cytology should be performed for dominant thyroid nodules discovered in pregnancy. Radioactive isotopes must be avoided during pregnancy and lactation. Universal screening of pregnant women for thyroid disease is not yet supported by adequate studies, but case finding targeted to specific groups of patients who are at increased risk is strongly supported.

EXECUTIVE SUMMARY

OVER THE PAST 15 yr there has been a rapid expansion of knowledge regarding thyroid disease and pregnancy. These advances relate to the optimal management of pregnant women on levothyroxine therapy, the impact of iodine deficiency on the mother and developing fetus, the adverse effect of maternal hypothyroidism on mental development in their infants, the syndrome of postpartum thyroiditis (PPT), and its relation to permanent hypothyroidism. Furthermore, a doubling of the miscarriage rate has been reported in studies in antibody-positive euthyroid women, and an increase in preterm delivery has been found in women with subclinical hypothyroidism and/or thyroid autoimmunity.

Given the rapidity of advances in this field, it is not surprising that controversy surrounds optimal detection and management of thyroid disease in the pregnant woman. Thyroid disease during pregnancy has certain characteristics that make writing guidelines more complicated than for some other fields. This field is concerned with the management of pregnant women who may have a variety of known or undisclosed thyroid conditions, such as hypothyroidism and hyperthyroidism, the presence of thyroid autoantibodies, the presence of nodules, or unsatisfactory iodine nutrition. Pregnancy may affect the course of these thyroid disorders, and conversely, thyroid diseases may affect the course of pregnancy. Moreover, thyroid disorders (and their management) may affect both the pregnant woman and the developing fetus. Finally, pregnant women may be under the care of multiple health care professionals, including obstetricians, nurse midwives, family practitioners, endocrinologists, and/or internists, making the development of guidelines all the more critical.

METHODS

An international task force was created, under the auspices of The Endocrine Society, to review the best evidence in the field and develop evidence-based guidelines. Members of the task force included representatives from The Endocrine Society, American Thyroid Association, Association of American Clinical Endocrinologists, European Thyroid Association, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. The task force worked during 2 yr to develop the guidelines, had multiple phone conversations, and two 2-d retreats. Upon completion of the guidelines, they were reviewed and approved by all of the participants.

Our committee undertook to review all material on these topics published in English during the past two decades, or earlier at the working group’s discretion. We concentrated on original reports and largely excluded reviews from our references. At present, with the exception of studies on iodide supplementation, only two prospective, randomized intervention trials have been published in this area. We are aware of two large-scale prospective intervention trials that are presently ongoing. Nevertheless, in the last 15 yr, many high-quality studies have modified older dogmas and profoundly changed the ways in which these patients are managed. These studies are most often prospective or retrospective clinical evaluations of a particular patient population and matched groups of control women. Such studies, when carefully performed, adequately matched, and appropriately interpreted, provide the bulk of the evidence presented herein.

The committee evaluated recommendations and evidence using the methodology of the United States Preventive Service Task Force (USPSTF), in which treatments or medical advice are referred to as a “service.” The USPSTF grades its recommendations (level A, B, C, D, or I) on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms), as follows.

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.

B. The USPSTF recommends that clinicians provide (the service) to eligible patients. The USPSTF found at least fair evidence that (the service) improves important health outcomes and concludes that benefits outweigh harms.

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.

D. The USPSTF recommends against routinely providing (the service) to asymptomatic patients. The USPSTF found good evidence that (the service) is ineffective or that harms outweigh benefits.

I. The USPSTF concludes that the 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.

The USPSTF grades the quality of the overall evidence for a service on a three-point scale (good, fair, or poor), defined as follows:

Good: Evidence includes consistent results from well designed, well conducted studies in representative populations that directly assess effects on health outcomes.

Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes.

Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

In addition to the USPSTF grading of recommendations, we have also included the appropriate recommendation level as indicated by the GRADE system. The value of an evidence-based recommendation, using the GRADE system, is scored from strong to moderate (1–2) and accompanied by symbols indicating the value of the evidence: high (1, ⊕⊕⊕⊕ or ⊕⊕⊕○), moderate (2, ⊕⊕○○), low (⊕○○○), and very low (○○○○). (There are no equivalents in the GRADE system for the recommendation levels C, D, and I used in the USPSTF system.)

The supporting data for the full committee report follow this executive summary. The supporting data consist of eight subsections dealing in detail with specific maternal/fetal thyroid problems. Each subsection provides the related background and evidence for recommendations. In the subsection reports, we have indicated specific bibliographic citations on which each recommendation is based, and for each report cited as evidence for a given recommendation, a short summary is provided. We believe that this approach provides an important direct link between the supporting evidence and the recommendation.

BACKGROUND AND EVIDENCE

The complete discussion of background data and evidence is offered in the supporting data that follow this executive summary. Some important issues are noted here.

Pregnant and lactating women require additional iodine intake, whether in iodine-poor or iodine-sufficient countries. The recommended average iodine intake is approximately 250 μg/d (1). Severe iodine deficiency, if inadequately treated, is a major cause of neurological damage worldwide (2).

Both overt and subclinical hypothyroidism have adverse effects on the course of pregnancy and development of the fetus (3–5). Hypothyroidism should be corrected before initiation of pregnancy, replacement dosage should be augmented early in pregnancy (6), and euthyroidism should be maintained throughout. Overt maternal hypothyroidism has been associated with damage to fetal intellectual development (7), presumably because of inadequate transplacental supply of hormone during early pregnancy (8). Whether subclinical hypothyroidism carries this risk remains unproven, but replacement therapy for this condition is nonetheless advised.

Propylthiouracil is recommended as the first-line drug for treatment of hyperthyroidism during pregnancy, because of the probable association of methimazole with fetal developmental abnormalities (9, 10). Maternal Graves’ disease, past or present, carries a risk for the pregnancy and for the fetus. Antithyroid drug (ATD) therapy to the mother can induce fetal hypothyroidism, and transplacental passage of TSH-receptor antibodies (TRAb) can cause fetal hyperthyroidism (11–13). Targeting ATD treatment to maintain maternal serum free T4 levels at the upper limit of the nonpregnant T4 range usually protects the fetus from hypothyroidism (14). Close following of maternal T4 and TSH levels, assay of TRAb, and fetal ultrasonography including the thyroid are recommended for guiding therapy (15), and fetal blood sampling is rarely needed (15, 16). Fetal hyperthyroidism does not occur during pregnancies in which TRAb levels are normal and ATD is not administered. Surgery may be required in some instances. Propylthiouracil, propranolol, and iodides may be used for preoperative preparation.

Hyperemesis is associated with elevation of thyroid hormone levels above average pregnancy values and suppression of TSH (17–19). Occasionally, patients are clinically thyrotoxic. The elevation of thyroid hormone levels and gestational hyperthyroidism are typically self-remitting and in most cases do not require antithyroid treatment (17, 20). Subclinical hyperthyroidism, commonly found in this setting, does not require therapy, and therapy is advised against because it might induce fetal hypothyroidism (21).

Thyroid nodules recognized during pregnancy, or growing, are typically biopsied under ultrasound guidance (22, 23), and if appropriate, surgery is performed in the mid-trimester (24). Delay in treatment of low-grade tumors until after delivery is not considered a danger (25). Pregnancy is not thought to adversely affect the course of thyroid malignancy (26–28). TSH suppression for known thyroid malignancy may be maintained during pregnancy with detectable TSH and with T4 at the upper end of the range for normal pregnancy. Radioactive iodine (RAI) must not be administered during pregnancy or lactation.

Autoimmune thyroid disease is common in pregnancy. The presence of antibodies to thyroid peroxidase or thyroglobulin is associated with a significant increment in miscarriages (29, 30). One prospective study has reported that treatment with T4 during pregnancy may reverse this risk (31). Additional studies on this important issue are needed.

PPT, a form of autoimmune thyroid disease closely related to Hashimoto’s thyroiditis, is found in about 7% of women in the postpartum period (32). It causes hyperthyroidism and/or hypothyroidism that is usually transient (but often seriously symptomatic) (33, 34) and increases the risk of later permanent hypothyroidism (35, 36). Although depression may be a symptom of hypothyroidism in any setting, PPT per se has not been clearly linked to postpartum depression (37, 38).

A major unsettled question is the advisability of universal screening of pregnant women for thyroid disease, through TSH testing, and possibly antibody testing. The prevalence of overt thyroid disease in this population is 1%, and there is also a 2–3% prevalence of subclinical hypothyroidism and 10–15% antibody positivity (30, 39). As of this date, only one study has demonstrated that treatment of antibody positive euthyroid women with T4 decreases the rate of miscarriage and preterm delivery (31). Thus, for now, the committee recommends targeted case finding during early pregnancy but anticipates that ongoing studies may alter this recommendation (40). Vaidya et al. (41) recently reported a study of screening by means of TSH, T4, free T4, and thyroid peroxidase antibodies in 1560 consecutive pregnant women. An important result was that screening only women considered high risk on the basis of a personal or family history of thyroid disease or a history of other autoimmune disease would have missed 30% of women with overt or subclinical hypothyroidism.

RECOMMENDATIONS

1. HYPOTHYROIDISM AND PREGNANCY: MATERNAL AND FETAL ASPECTS

1.1.1. Both maternal and fetal hypothyroidism are known to have serious adverse effects on the fetus. Therefore maternal hypothyroidism should be avoided. USPSTF recommendation level is A; evidence is fair (GRADE 1|⊕⊕⊕○). Targeted case finding is recommended at the first prenatal visit or at diagnosis of pregnancy (see Section 8, Screening for thyroid dysfunction during pregnancy). USPSTF recommendation level is B; evidence is fair (GRADE 2|⊕⊕○○).

1.1.2. If hypothyroidism has been diagnosed before pregnancy, we recommend adjustment of the preconception T4 dose to reach a TSH level not higher than 2.5 μU/ml before pregnancy. USPSTF recommendation level is I; evidence is poor (⊕○○○).

1.1.3. The T4 dose usually needs to be incremented by 4–6 wk gestation and may require a 30–50% increase in dosage. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕).

1.1.4. If overt hypothyroidism is diagnosed during pregnancy, thyroid function tests should be normalized as rapidly as possible. The T4 dosage should be titrated to rapidly reach and thereafter maintain serum TSH concentrations of less than 2.5 μU/ml in the first trimester (or 3 μU/ml in the second and third trimesters) or to trimester-specific normal TSH ranges. Thyroid function tests should be remeasured within 30–40 d. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕).

1.1.5. Women with thyroid autoimmunity who are euthyroid in the early stages of pregnancy are at risk of developing hypothyroidism and should be monitored for elevation of TSH above the normal range. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕○).

1.1.6. Subclinical hypothyroidism (serum TSH concentration above the upper limit of the reference range with a normal free T4) has been shown to be associated with an adverse outcome for both the mother and offspring. T4 treatment has been shown to improve obstetrical outcome but has not been proved to modify long-term neurological development in the offspring. However, given that the potential benefits outweigh the potential risks, the panel recommends T4 replacement in women with subclinical hypothyroidism. For obstetrical outcome, USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕○○). For neurological outcome, USPSTF recommendation level is I; evidence is poor (○○○○).

1.1.7. After delivery, most hypothyroid women need a decrease in the T4 dosage they received during pregnancy. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕).

2. MANAGEMENT OF MATERNAL HYPERTHYROIDISM: MATERNAL (A) AND FETAL (B) ASPECTS

2.1.a.1. If a subnormal serum TSH concentration is detected during gestation, hyperthyroidism must be distinguished from both normal physiology during pregnancy and hyperemesis gravidarum because of the adverse effects of overt hyperthyroidism on the mother and fetus. Differentiation of Graves’ disease from gestational thyrotoxicosis is supported by evidence of autoimmunity, a goiter, and presence of TRAb. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕).

2.1.a.2. For overt hyperthyroidism due to Graves’ disease or hyperfunctioning thyroid nodules, ATD therapy should be either initiated (for those with new diagnoses) or adjusted (for those with a prior history) to maintain the maternal thyroid hormone levels for free T4 in the upper nonpregnant reference range. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕).

2.1.a.3. Because available evidence suggests methimazole may be associated with congenital anomalies, propylthiouracil should be used as a first-line drug, if available, especially during first-trimester organogenesis. Methimazole may be prescribed if propylthiouracil is not available or if a patient cannot tolerate or has an adverse response to propylthiouracil. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕○○).

2.1.a.4. Subtotal thyroidectomy may be indicated during pregnancy as therapy for maternal Graves’ disease if 1) a patient has a severe adverse reaction to ATD therapy, 2) persistently high doses of ATD are required, or 3) a patient is not adherent to ATD therapy and has uncontrolled hyperthyroidism. The optimal timing of surgery is in the second trimester. USPSTF recommendation level is I; evidence is poor (⊕○○○).

2.1.a.5. There is no evidence that treatment of subclinical hyperthyroidism improves pregnancy outcome, and treatment could potentially adversely affect fetal outcome. USPSTF recommendation level is I; evidence is poor (⊕○○○).

2.1.b.1 TRAb (either TSH receptor-stimulating or -binding antibodies) freely cross the placenta and can stimulate the fetal thyroid. These antibodies should be measured before pregnancy or by the end of the second trimester in mothers with current Graves’ disease, with a history of Graves’ disease and treatment with 131I or thyroidectomy, or with a previous neonate with Graves’ disease. Women who have a negative TRAb and do not require ATD have a very low risk of fetal or neonatal thyroid dysfunction. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕⊕○).

2.1.b.2. 131I should not be given to a woman who is or may be pregnant. If inadvertently treated, the patient should be promptly informed of the radiation danger to the fetus, including thyroid destruction if treated after the 12th week of gestation. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕). There are no data for or against recommending termination of pregnancy after 131I exposure. USPSTF recommendation level is I; evidence is poor (⊕○○○).

2.1.b.3. In women with elevated TRAb or in women treated with ATD, fetal ultrasound should be performed to look for evidence of fetal thyroid dysfunction that could include growth restriction, hydrops, presence of goiter, or cardiac failure. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕⊕○).

2.1.b.4. Umbilical blood sampling should be considered only if the diagnosis of fetal thyroid disease is not reasonably certain from the clinical data and if the information gained would change the treatment. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕⊕○).

2.1.b.5. All newborns of mothers with Graves’ disease should be evaluated for thyroid dysfunction and treated if necessary. USPSTF recommendation level is B; evidence is fair (GRADE 2|⊕○○○).

3. GESTATIONAL HYPEREMESIS AND HYPERTHYROIDISM

3.1. Thyroid function tests should be measured in all patients with hyperemesis gravidarum (5% weight loss, dehydration, and ketonuria) USPSTF recommendation level is B; evidence is poor (GRADE 2|⊕○○○).

3.2. Few women with hyperemesis gravidarum will require ATD treatment. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕). Overt hyperthyroidism believed due to coincident Graves’ disease should be treated with ATD. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕⊕○). Gestational hyperthyroidism with clearly elevated thyroid hormone levels (free T4 above the reference range or total T4 > 150% of top normal pregnancy value and TSH < 0.1 μU/ml) and evidence of hyperthyroidism may require treatment as long as clinically necessary. USPSTF recommendation level is I; evidence is poor (⊕○○○).

4. AUTOIMMUNE THYROID DISEASE AND MISCARRIAGE

4.1. Although a positive association exists between the presence of thyroid antibodies and pregnancy loss, universal screening for antithyroid antibodies and possible treatment cannot be recommended at this time. As of this date, only one adequately designed intervention trial has demonstrated a decrease in the miscarriage rate in thyroid antibody-positive euthyroid women. USPSTF recommendation level is C; evidence is fair (GRADE 2|⊕○○○).

5. THYROID NODULES AND CANCER

5.1. Fine-needle aspiration (FNA) cytology should be performed for thyroid nodules larger than 1 cm discovered in pregnancy. Ultrasound-guided FNA may have an advantage for minimizing inadequate sampling. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕⊕○).

5.2. When nodules are discovered in the first or early second trimester to be malignant on cytopathological analysis or exhibit rapid growth, pregnancy should not be interrupted, but surgery should be offered in the second trimester before fetal viability. Women found to have cytology indicative of papillary cancer or follicular neoplasm without evidence of advanced disease who prefer to wait until the postpartum period for definitive surgery may be reassured that most well differentiated thyroid cancers are slow growing and that surgical treatment soon after delivery is unlikely to adversely affect prognosis. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕○○).

5.3. It is appropriate to administer thyroid hormone to achieve a suppressed but detectable TSH in pregnant women with a previously treated thyroid cancer or an FNA positive for or suspicious for cancer and those who elect to delay surgical treatment until postpartum. High-risk patients may benefit from a greater degree of TSH suppression compared with low-risk patients. The free T4 or total T4 levels should ideally not be increased above the normal range for pregnancy. USPSTF recommendation level is I; evidence is poor (⊕○○○).

5.4. RAI administration with 131I should not be given to women who are breastfeeding. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕⊕⊕). Furthermore, pregnancy should be avoided for 6 months to 1 yr in women with thyroid cancer who receive therapeutic RAI doses to ensure stability of thyroid function and confirm remission of thyroid cancer. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕○○).

6. IODINE NUTRITION DURING PREGNANCY

6.1. Women of childbearing age should have an average iodine intake of 150 μg/d. During pregnancy and breastfeeding, women should increase their daily iodine intake to 250 μg on average. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕○).

6.2. Iodine intake during pregnancy and breastfeeding should not exceed twice the daily recommended nutritional intake for iodine, i.e. 500 μg iodine per day. USPSTF recommendation level is I; evidence is poor (⊕○○○).

6.3. To assess the adequacy of the iodine intake during pregnancy in a population, urinary iodine concentration should be measured in a cohort of the population. Urinary iodine concentration should ideally range between 150 and 250 μg/liter. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕).

6.4. To reach the daily recommended nutrient intake for iodine, multiple means must be considered, tailored to the iodine intake level in a given population. Different situations must therefore be distinguished: 1) countries with iodine sufficiency and/or with a well established universal salt iodization (USI) program, 2) countries without a USI program or an established USI program where the coverage is known to be only partial, and finally 3) remote areas with no accessible USI program and difficult socioeconomic conditions. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕⊕).

7. POSTPARTUM THYROIDITIS

7.1. There are insufficient data to recommend screening of all women for PPT. USPSTF recommendation level is I; evidence is poor (⊕○○○).

7.2. Women known to be thyroid peroxidase antibody positive should have a TSH performed at 3 and 6 months postpartum USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕○).

7.3. The prevalence of PPT in women with type 1 diabetes is 3-fold greater than in the general population. Postpartum screening (TSH determination) is recommended for women with type 1 diabetes mellitus at 3 and 6 months postpartum. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕○○).

7.4. Women with a history of PPT have a markedly increased risk of developing permanent primary hypothyroidism in the 5- to 10-yr period after the episode of PPT. An annual TSH level should be performed in these women. USPSTF recommendation level is A; evidence is good (GRADE 1|⊕⊕⊕○).

7.5. Asymptomatic women with PPT who have a TSH above the reference range but less than 10 μU/ml and who are not planning a subsequent pregnancy do not necessarily require intervention but should, if untreated, be remonitored in 4–8 wk. Symptomatic women and women with a TSH above normal and who are attempting pregnancy should be treated with levothyroxine. USPSTF recommendation level is B; evidence is fair (⊕⊕○○).

7.6. There is insufficient evidence to conclude whether an association exists between postpartum depression and either PPT or thyroid antibody positivity (in women who did not develop PPT). USPSTF recommendation level is I; evidence is poor (○○○○).

However, because hypothyroidism is a potentially reversible cause of depression, women with postpartum depression should be screened for hypothyroidism and appropriately treated. USPSTF recommendation level is B; evidence is fair (GRADE 2|⊕⊕○○).

8. SCREENING FOR THYROID DYSFUNCTION DURING PREGNANCY

Although the benefits of universal screening for thyroid dysfunction (primarily hypothyroidism) may not be justified by the current evidence (presented above), we recommend case finding among the following groups of women at high risk for thyroid disease by measurement of TSH:

1. Women with a history of hyperthyroid or hypothyroid disease, PPT, or thyroid lobectomy.

2. Women with a family history of thyroid disease.

3. Women with a goiter.

4. Women with thyroid antibodies (when known).

5. Women with symptoms or clinical signs suggestive of thyroid underfunction or overfunction, including anemia, elevated cholesterol, and hyponatremia.

6. Women with type I diabetes.

7. Women with other autoimmune disorders.

8. Women with infertility who should have screening with TSH as part of their infertility work-up.

9. Women with previous therapeutic head or neck irradiation.

10. Women with a history of miscarriage or preterm delivery. USPSTF recommendation level is B; evidence is fair (GRADE 1|⊕⊕○○).

Acknowledgments

Co-sponsors: American Association of Clinical Endocrinology (A.A.C.E.), Asia & Oceana Thyroid Association (A.O.T.A.), American Thyroid Association (A.T.A.), European Thyroid Association (E.T.A.), Latin American Thyroid Association (L.A.T.A)

The members of the Task Force thank Dr. Robert Vigersky, the members of the Clinical Guidelines Subcommittee, the Clinical Affairs Committee, and The Endocrine Society’s Council for their careful review of earlier versions of this manuscript and their helpful suggestions. We thank Patricia A. Stephens, Ph.D., medical writer on this guideline, who meticulously checked the references and formatted the guideline into its current form. We thank the many members of The Endocrine Society who reviewed the draft version of this manuscript when it was posted on the Society web site and who sent a great number of additional comments, most of which were incorporated into the final version of the manuscript. In addition, we thank the leadership of the American Association of Clinical Endocrinology, Asia & Oceana Thyroid Association, American Thyroid Association, European Thyroid Association, and the Latin American Thyroid Association, for having the foresight to endorse this important document and for providing us with some of their most qualified experts in the field. Finally, we thank the staff at The Endocrine Society office for their helpful support during the development of this Guideline.

Financial Disclosure of Writing Task Force

Leslie J. DeGroot, MD (chair)—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: Occasional consultant with Abbott Laboratories; Grant or Other Research Support: None Declared; Other: Grant support to http://Thyroidmanager.org Web site by Abbott Laboratories. Marcos S. Abalovich, MD—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: None Declared; Grant or Other Research Support: None Declared. Nobuyuki Amino, MD, PhD—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: None Declared; Grant or Other Research Support: None Declared. Linda A. Barbour, MSPH, MD—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: None Declared; Grant or Other Research Support: None Declared. Rhoda H. Cobin, MD—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: None Declared; Grant or Other Research Support: None Declared. Daniel Glinoer, MD, PhD—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: None Declared; Grant or Other Research Support: Ministère de la Communauté Française (Administration Générale de l’Enseignement et de la Recherche Scientifique) within the framework of A.R.C. (Actions de Recherche Concertée; convention N° 04/09-314). Susan J. Mandel, MD, MPH—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: King Pharmaceuticals; Grant or Other Research Support: None Declared. Alex Stagnaro-Green, MD—Significant Financial Interests: None Declared; Governance: None Declared; Consultation or Advisement: None Declared; Grant or Other Research Support: None Declared.

DISCLAIMER: Clinical Practice Guidelines are developed to be of assistance to endocrinologists by providing guidance and recommendations for particular areas of practice. The Guidelines should not be considered inclusive of all proper approaches or methods, or exclusive of others. The Guidelines cannot guarantee any specific outcome, nor do they establish a standard of care. The Guidelines are not intended to dictate the treatment of a particular patient. Treatment decisions must be made based on the independent judgment of healthcare providers and each patient’s individual circumstances.

The Endocrine Society makes no warranty, express or implied, regarding the Guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. The Society shall not be liable for direct, indirect, special, incidental, or consequential damages related to the use of the information contained herein.

Abbreviations:

ATD,
FNA,
PPT,
RAI,
TRAb,
USI,
universal salt iodization;
USPSTF,
United States Preventive Service Task Force.

World Health Organization, Technical consultation of experts in Geneva in January

2005

The prevention and control of iodine deficiency in pregnant and lactating women and in children under two years: recommendations of a WHO Technical Consultation

Public Health Nutr

in press

Bleichrodt

Born

1994

A meta-analysis of research on iodine and its relationship to cognitive development

In: Stanbury JB, ed. The damaged brain of iodine deficiency: cognitive, behavioral, neuromotor, educative aspects. New York: Cognizant Communication;

195

–

200

Davis

Leveno

Cunningham

1988

Hypothyroidism complicating pregnancy.

Obstet Gynecol

108

–

112

Leung

Millar

Koonings

Montoro

Mestman

1993

Perinatal outcome in hypothyroid pregnancies.

Obstet Gynecol

349

–

353

Wasserstrum

Anania

1995

Perinatal consequences of maternal hypothyroidism in early pregnancy and inadequate replacement.

Clin Endocrinol (Oxf)

353

–

358

Alexander

Marqusee

Lawrence

Jarolim

Fischer

Larsen

2004

Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism.

N Engl J Med

351

241

–

249

Haddow

Palomaki

Allan

Williams

Knight

Gagnon

O’Heir

Mitchell

Hermos

Waisbren

Faix

Klein

1999

Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.

N Engl J Med

341

549

–

555

Kester

Martinez de Mena

Obregon

Marinkovic

Howatson

Visser

Hume

Morreale de Escobar

2004

Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas.

J Clin Endocrinol Metab

3117

–

3128

Clementi

Di Gianantonio

Pelo

Mammi

Basile

Tenconi

1999

Methimazole embryopathy: delineation of the phenotype.

Am J Med Genet

–

Johnsson

Larsson

Ljunggren

1997

Severe malformations in infant born to hyperthyroid woman on methimazole

Lancet

350

1520

Peleg

Cada

Peleg

Ben-Ami

2002

The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis.

Obstet Gynecol

1040

–

1043

Weetman

2000

Graves’ disease.

N Engl J Med

343

1236

–

1248

McKenzie

Zakarija

1992

Fetal and neonatal hyperthyroidism and hypothyroidism due to maternal TSH receptor antibodies.

Thyroid

155

–

159

Momotani

Noh

Ishikawa

Ito

1997

Effects of propylthiouracil and methimazole on fetal thyroid status in mothers with Graves’ hyperthyroidism.

J Clin Endocrinol Metab

3633

–

3636

Luton

Le Gac

Vuillard

Castanet

Guibourdenche

Noel

Toubert

Leger

Boissinot

Schlageter

Garel

Tebeka

Oury

Czernichow

Polak

2005

Management of Graves’ disease during pregnancy: the key role of fetal thyroid gland monitoring.

J Clin Endocrinol Metab

6093

–

6098

Laurberg

Nygaard

Glinoer

Grussendorf

Orgiazzi

1998

Guidelines for TSH-receptor antibody measurements in pregnancy: results of an evidence-based symposium organized by the European Thyroid Association.

Eur J Endocrinol

139

584

–

586

Goodwin

Montoro

Mestman

1992

Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects.

Am J Obstet Gynecol

167

648

–

652

Al-Yatama

Diejomaoh

Nandakumaran

Monem

Omu

Al Kandari

2002

Hormone profile of Kuwaiti women with hyperemesis gravidarum.

Arch Gynecol Obstet

266

218

–

222

Leylek

Cetin

Toyaksi

Erselcan

1996

Hyperthyroidism in hyperemesis gravidarum.

Int J Gynaecol Obstet

–

Tan

Loh

Yeo

Chee

2002

Transient hyperthyroidism of hyperemesis gravidarum.

BJOG

109

683

–

688

Casey

Dashe

Wells

McIntire

Leveno

Cunningham

2006

Subclinical hyperthyroidism and pregnancy outcomes.

Obstet Gynecol

107

337

–

341

Choe

McDougall

1994

Thyroid cancer in pregnant women: diagnostic and therapeutic management.

Thyroid

433

–

435

Rosen

Korman

Walfish

1997

Thyroid nodular disease in pregnancy: current diagnosis and management.

Clin Obstet Gynecol

–

Sam

Molitch

2003

Timing and special concerns regarding endocrine surgery during pregnancy.

Endocrinol Metab Clin North Am

337

–

354

Doherty

Shindo

Rice

Montero

Mestman

1995

Management of thyroid nodules during pregnancy.

Laryngoscope

105

251

–

255

Moosa

Mazzaferri

1997

Outcome of differentiated thyroid cancer diagnosed in pregnant women.

J Clin Endocrinol Metab

2862

–

2866

Herzon

Morris

Segal

Rauch

Parnell

1994

Coexistent thyroid cancer and pregnancy.

Arch Otolaryngol Head Neck Surg

120

1191

–

1193

Schlumberger

De Vathaire

Ceccarelli

Francese

Pinchera

Parmentier

1995

Outcome of pregnancy in women with thyroid carcinoma.

J Endocrinol Invest

150

–

151

Glinoer

Soto

Bourdoux

Lejeune

Delange

Lemone

Kinthaert

Robijn

Grun

de Nayer

1991

Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions.

J Clin Endocrinol Metab

421

–

427

Stagnaro-Green

Roman

Cobin

el-Harazy

Alvarez-Marfany

Davies

1990

Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies.

JAMA

264

1422

–

1425

Negro

Formoso

Mangieri

Pezzarossa

Dazzi

Hassan

2006

Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications.

J Clin Endocrinol Metab

2587

–

2591

Amino

Tada

Hidaka

1999

Postpartum autoimmune thyroid syndrome: a model of aggravation of autoimmune disease.

Thyroid

705

–

713

Stagnaro-Green

2002

Postpartum thyroiditis.

J Clin Endocrinol Metab

4042

–

4047

Lucas

Pizarro

Granada

Salinas

Foz

Sanmarti

2000

Postpartum thyroiditis: epidemiology and clinical evolution in a nonselected population.

Thyroid

–

Othman

Phillips

Parkes

Richards

Harris

Fung

Darke

John

Hall

Lazarus

1990

A long-term follow-up of postpartum thyroiditis.

Clin Endocrinol (Oxf)

559

–

564

Tachi

Amino

Tamaki

Aozasa

Iwatani

Miyai

1988

Long term follow-up and HLA association in patients with postpartum hypothyroidism.

J Clin Endocrinol Metab

480

–

484

Kent

Stuckey

Allen

Lambert

Gee

1999

Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity.

Clin Endocrinol (Oxf)

429

–

438

Lucas

Pizarro

Granada

Salinas

Sanmarti

2001

Postpartum thyroid dysfunction and postpartum depression: are they two linked disorders?

Clin Endocrinol (Oxf)

809

–

814

Allan

Haddow

Palomaki

Williams

Mitchell

Hermos

Faix

Klein

2000

Maternal thyroid deficiency and pregnancy complications: implications for population screening.

J Med Screen

127

–

130

Lazarus

Premawardhana

2005

Screening for thyroid disease in pregnancy.

J Clin Pathol

449

–

452

Vaidya

Anthony

Bilous

Shields

Drury

Hutchinson

and Bilous

2007

Detection of thyroid dysfunction in early pregnancy: universal screening or targeted high-risk case finding.

J Clin Endocrinol Metab

203

–

207