Best Practice & Research Clinical Endocrinology & Metabolism
6Thyroid disease in pregnancy
Introduction
Thyroid disease in pregnancy is common. At least 2–3% of women are affected by thyroid dysfunction and around 10% suffer from autoimmune thyroid disease despite euthyroidism. In the last twenty years, the understanding of thyroid physiology in pregnancy and the association between thyroid dysfunction and obstetrical/neonatal adverse outcomes have greatly improved and, as a result, the scientific community has released specific guidelines. The first guidelines, endorsed by the Endocrine Society, were published in 2007 and, just three years later, these will be updated. Concurrently, the American Thyroid Association recently released its own guidelines this year. Pregnancy influences thyroid function and untreated thyroid dysfunction (hyperthyroidism or hypothyroidism) is associated with increased rate of adverse outcomes. This raises the need for an awareness of thyroid disease in pregnancy with the aim of reducing the rate of complications. Furthermore, this field involves different patients (i.e., the pregnant woman and, indirectly, the fetus) as well as different specialists, namely obstetricians and endocrinologists. Therefore, appropriate knowledge is necessary for proper management.
In this paper, we aimed to summarise and translate the results of the literature into evidence-based and clinically useful practical recommendations. The key clinical issues of diagnosis, treatment and patient management were addressed in order to help the endocrinologist in decision-making processes. Management of thyroid disease in pregnancy is an evolving field, still characterized by areas of uncertainty. Ongoing studies over the next few years will hopefully provide definitive answers to unresolved questions.
Section snippets
Thyroid function test in pregnancy
Following conception, circulating total T4 and thyroxine binding globulin (TBG) concentrations increase at around 4–8 weeks. The thyrotropic activity of human chorionic gonadotropin (hCG) causes a decrease in serum thyroid-stimulating hormone (TSH) in the first trimester so that pregnant women have lower serum TSH concentrations than non-pregnant women.1, 2 Many studies also report a substantial decrease in serum-free thyroxine (FT4) concentrations with progression of gestation, even though
Overt hypothyroidism
Overt hypothyroidism (OH) is defined as a low FT4 with high TSH levels.
While worldwide iodine deficiency is the main cause of OH, in areas where iodine intake is sufficient, the most frequent cause is autoimmune thyroiditis. Other causes are prior thyroidectomy, radioiodine therapy, the use of drugs such as amiodarone, anti-thyroid drugs and lithium, congenital hypothyroidism, pituitary or hypothalamic disease, and immunoglobulin binding to the TSH receptor (blocking its activity). The
Subclinical hypothyroidism
Subclinical hypothyroidism (SH) is defined as a normal FT4 with high TSH levels. SH is by far the most frequent thyroid dysfunction occurring in pregnancy. The prevalence of SH varies from one study to another, depending on the definition of SH, ethnicity, iodine intake, and study design. In most cases, prevalence is between 1.5 and 4.0%.7, 8, 9, *10
As with OH, SH also has several obstetrical complications associated with the condition. Findings from various studies are unclear, perhaps due to
Thyroid autoimmunity
Positivity for thyroid antibodies is quite a common finding in women of childbearing age, accounting around 10%, and is by far the most common autoimmune disease.
Stagnaro-Green et al. published the first paper to demonstrate an association between pregnancy loss and thyroid antibodies.26 The authors, evaluating the course of 550 pregnancies, serendipitously found that patients who were positive for Tg-Ab or TPOAb had a 2-fold increase in the risk of pregnancy loss (17% vs 8.4%). Since then,
Isolated hypothyroxinemia
The condition of isolated hypothyroxinemia in pregnancy is defined as the presence of an FT4 value below the 2.5th percentile with a TSH level within the normal range.
The leading cause of IH is iodine deficiency. The National Health and Nutrition Examination Survey 2003–2004 demonstrated that the population in the United States was generally iodine sufficient, as measured by urinary iodine concentration (UIC = 160 μg/L), but showed that low UIC values (<50 μg/L) were found in 11.3% of the
Hyperthyroidism
Hyperthyroidism is defined as an excessive production of thyroid hormones by the thyroid gland. Causes of hyperthyroidism may be mainly divided into (1) immune and (2) non-immune thyroid disease. Graves’ disease is an autoimmune disease and may result in maternal and fetal complications if not properly controlled. The most common cause of non-immune hyperthyroidism is “Transient Hyperthyroidism of Hyperemesis Gravidarum” (THHG), defined as “transient hyperthyroidism, limited to the first
Clinical presentation
Diagnosis of non-immune Transient Hyperthyroidism is confirmed by the presence of suppressed or undetectable serum TSH levels in the presence of elevated FT4. Since the low-normal range of serum TSH in normal first trimester pregnancy may be as low as 0.03 mIU/L, an elevated serum FT4 is necessary for the diagnosis.52 This is due to a significant increase concentration of human Chorionic Gonadotrophin (hCG) above normal levels for pregnancy or hCG abnormal molecular variants with higher
Management
Effective treatment of hyperthyroidism is paramount to prevent maternal, fetal, and neonatal complications. ATDs remain the treatment of choice. The goal is to use the lowest possible dose of anti-thyroid medication necessary to maintain FT4 levels in the upper one-third of the normal non-pregnant range or just above the normal range.70 Excessive doses of ATDs may affect fetal thyroid function, with the development of hypothyroidism and/or goiter.71, 72 The dose of ATD should be adjusted every
Summary
In summary, knowledge of the interplay between thyroid function and pregnancy is becoming even more extensive but several points still need to be clarified. A TSH trimester-specific range should be applied to correctly interpret thyroid function during pregnancy. The upper limit of TSH in the first trimester should be 2.5 mIU/L, and 3.0 mIU/L in the second and the third trimesters; low-normal TSH concentrations in the first trimester should be considered physiological. While subclinical
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2022, Preventive MedicineCitation Excerpt :At least two potential explanations for this finding exist. First, thyroid disease is common among women of reproductive age and thyroid disfunction is known to increase the risk of pregnancy losses and other adverse outcomes (Negro and Mestman, 2011; Mannisto et al., 2013). Therefore, women undergoing treatment for thyroid disease diagnosed before pregnancy may be more likely to be counseled on the importance of maintaining thyroid levels before and during pregnancy, and may also be in regular care for their thyroid disorder.
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