Thyroid Dysfunction and Pregnancy: Where Are We Five Years Later?

Abstract

This issue of the JCEM presents new guidelines for addressing thyroid dysfunction during pregnancy and the postpartum period (1). These guidelines follow on those published 5 yr ago, highlighting the importance of this topic and reflecting the knowledge gained in the last few years. The text discusses and gives recommendations related to maternal and fetal aspects of hypothyroidism, hyperthyroidism, autoimmunity, thyroid nodules and cancer, iodine nutrition, and postpartum thyroiditis. A final paragraph is dedicated to the issue of screening for thyroid dysfunction in pregnancy. As in the previous version, the new guidelines focus attention on either the pregnant woman or the fetus; there is no doubt that in this field, we need more randomized controlled trials (RCT) to assess the obstetrical impact of thyroid disease, but also studies that evaluate long-term outcomes such as child intelligence quotient (IQ), especially in cases of maternal subclinical hypothyroidism (2). Of about 140 references in the new guidelines, 20% date from 2007 (the year the previous guidelines were published). What have these new references added, and what are the gray areas that require further investigation? The present guidelines confirm the suggestion of treating subclinical autoimmune hypothyroidism with levothyroxine (LT4) because the potential benefits from treatment outweigh the risk of potential adverse events. Association studies have yielded conflicting results regarding outcomes such as miscarriage, hypertension, placental abruption, and preterm delivery, and to date, one singlecenter RCT has demonstrated a significant reduction in obstetrical and neonatal complications when subclinically hypothyroid women are treated from the first trimester (3, 4). The panel also recommends treating antibody-negative women who have subclinical hypothyroidism. Despite the absence of relevant RCT, this recommendation seems reasonable given that independent of thyroid autoimmunity, an increased TSH level is associated with a miscarriage risk, and an elevated TSH at the beginning of pregnancy may predispose the mother to further impairment of thyroid function in the following months. “Partial replacement therapy” with LT4 is also suggested in cases of isolated hypothyroxinemia, although at the discretion of the physician. This recommendation directly leads to another point examined in the guidelines: awareness about the possible inaccuracy of serum free T4 (FT4) measurement in pregnancy. The absence of a universally accepted trimester-specific reference range (and the common absence of each single laboratory-specific reference range) is an issue that makes defining cutoff values difficult and complicates clear identification of isolated hypothyroxinemia as a clinical entity. The issue of the potential inaccuracy of FT4 dosage, other than complicating the distinction between subclinical and overt hypothyroidism, is also reported in the hyperthyroidism section, where the guidelines recommend maintaining maternal thyroid FT4 levels at the upper limit of the nonpregnant reference range. An alternative suggestion is to use total T4, or the free T4 index (“adjusted T4”), at 1.5-fold the upper limit, given that many laboratories unfortunately have definitively dismissed total T4 measurement. Regarding hyperthyroidism, the new guidelines confirm the suggestion of using propylthiouracil in the first trimester and methimazole (MMI) in the second and the third trimesters because of the increased risk of malformations associated with the use of MMI [further confirmed by a very recent paper published in the JCEM (5)]. Like the American Thyroid Association (ATA)-American Association of Clinical Endocrinologists (AACE) guide-