THYROID SPECIAL ARTICLE Volume 27, Number 3, 2017 ª American Thyroid Association ª Mary Ann Liebert, Inc. DOI: 10.1089/thy.2016.0457 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum Erik K. Alexander,1,* Elizabeth N. Pearce,2,* Gregory A. Brent,3 Rosalind S. Brown,4 Herbert Chen,5 Chrysoula Dosiou,6 William A. Grobman,7 Peter Laurberg,8,{ John H. Lazarus,9 Susan J. Mandel,10 Robin P. Peeters,11 and Scott Sullivan12 Background: Thyroid disease in pregnancy is a common clinical problem. Since the guidelines for the man- agement of these disorders by the American Thyroid Association (ATA) were first published in 2011, signif- icant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid disease in women during pregnancy, preconception, and the postpartum period. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant cita- tions, and critical appraisal of selected studies. Published English language articles were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. The guideline task force had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communi- cated to the ATA and task force members. Results: The revised guidelines for the management of thyroid disease in pregnancy include recommendations regarding the interpretation of thyroid function tests in pregnancy, iodine nutrition, thyroid autoantibodies and pregnancy complications, thyroid considerations in infertile women, hypothyroidism in pregnancy, thyrotoxi- cosis in pregnancy, thyroid nodules and cancer in pregnant women, fetal and neonatal considerations, thyroid disease and lactation, screening for thyroid dysfunction in pregnancy, and directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders. Keywords: pregnancy, thyroid and pregnancy, thyroid function tests, postpartum thyroiditis 1Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts. 2Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts. 3Department of Medicine, VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles, California. 4Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts. 5Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. 6Division of Endocrinology, Stanford University School of Medicine, Stanford, California. 7Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois. 8Departments of Endocrinology & Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark. 9Institute of Molecular Medicine, Cardiff University, Cardiff, United Kingdom. 10Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 11Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands. 12Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina. *Co-chairpersons: Erik K. Alexander and Elizabeth N. Pearce. Excepting the co-chairpersons, the authors are listed in alphabetical order and were appointed by the ATA to independently formulate the content of this manuscript. None of the scientific or medical content of the manuscript was dictated by the ATA. {Deceased. 315 316 ALEXANDER ET AL. DEDICATION mixed conclusions. Several ongoing investigations will shed These guidelines are dedicated to the memory of Dr. Peter further light on this difficult question. Laurberg, our friend and colleague, who died tragically Given the complexity surrounding thyroid physiology and during their preparation. thyroid illness during pregnancy and the postpartum period, how and when to evaluate for thyroid dysfunction and how and if to treat thyroid illness during this period remain I. INTRODUCTION challenging. In 2011, the American Thyroid Association (ATA) first regnancy has a profound impact on the thyroid gland published guidelines on the diagnosis and management of Pand its function. During pregnancy, the thyroid gland thyroid disease during pregnancy and postpartum (1). There increases in size by 10% in iodine replete countries but by has been a substantial amount of new literature in this area 20% to 40% in areas of iodine deficiency. Production of the since that publication. thyroid hormones, thyroxine (T4), and triiodothyronine (T3), It is in this context that the ATA charged a task force to increases by nearly 50%, in conjunction with a separate 50% develop revised clinical guidelines on the diagnosis and increase in the daily iodine requirement. These physiological treatment of thyroid disease during pregnancy and the post- changes happen seamlessly in healthy women, but thyroid partum period. The task force consisted of both national and dysfunction can occur in many pregnant women because of international experts in the field of thyroid disease and pathologic processes. Furthermore, other thyroid illnesses pregnancy and included representatives from the ATA, the such as nodular disease and thyroid cancer are occasionally European Thyroid Association (ETA), the American College detected during pregnancy and may require treatment. To- of Obstetricians and Gynecologists, the Society for Maternal gether, the burden of thyroid disease affecting women, either Fetal Medicine, and the Iodine Global Network. In addition before, during, or directly after pregnancy, is substantial. to evidence-based updates of traditional content areas, the For these reasons thyroid function is frequently assessed task force also sought to expand the prior document to ad- during the gestation period. However, accurate assessment of dress topics such as thyroid disease during lactation, the maternal (and fetal) thyroid function during pregnancy re- treatment of thyroid illness in infertile women and those mains difficult, and interpretation of laboratory testing differs undergoing assisted reproductive techniques (ART), as well from the nonpregnant patient. Placental human chorionic as the approach to thyroid disease in the newborn. gonadotropin (hCG) stimulates thyroid hormone secretion, The literature review for each section included an analysis often decreasing maternal thyrotropin (TSH) concentrations, of all primary studies in the area published since 1990 and especially in early pregnancy. But while such transiently selective review of the primary literature published prior to suppressed maternal TSH concentrations are often observed 1990 that was seminal in the field. In the past 25 years, there and deemed safe, defining the upper reference limit for serum have been a number of recommendations and guideline TSH in this population has remained controversial. Further- statements relating to aspects of thyroid disease and preg- more, up to 18% of all pregnant women are thyroid peroxi- nancy. In deriving the present guidelines, the task force dase antibody (TPOAb) or thyroglobulin antibody (TgAb) conducted a new and comprehensive analysis of the primary positive. Increasingly, data suggest that TPOAb positivity literature and reformulated all clinical recommendations. In adversely modulates the impact of maternal thyroid status doing so, this document represents the best effort to create a (especially hypothyroidism) on the pregnancy and the de- useful, practical, and accurate guideline designed to help the veloping fetus. Thyroid antibody positivity separately in- practicing clinician, while also stimulating future research creases the risk of thyroid dysfunction following delivery and and discovery into this important and complex arena. during the postpartum period. Studies have recently questioned the optimal treatment of II. METHODS hyperthyroidism during pregnancy. Clinical management of patients with Graves’ disease (GD) is challenged by the un- ATA Thyroid Disease in Pregnancy guidelines were pre- derstanding that maternal antibodies as well as antithyroid viously published in 2011 (1). Because of the rapid growth of medication may differentially affect maternal and fetal thy- the literature relating to this topic, plans for revising the roid function. Reports have also detailed the potential tera- guidelines within *4–5 years of publication were made at togenic effects of the antithyroid medications methimazole the inception of the project. Task force chairs were appointed (MMI) and propylthiouracil (PTU). But while mild hyper- by the ATA President with approval of the Board. A task thyroidism appears safe