Autoimmune Thyroid Disease and Pregnancy

The defect that predisposes an individual to develop autoimmune thyroid disease is still unknown. Proposed mechanisms include a tissue-specific defect in suppressor T-cell activity, a genetically programmed presentation of a thyroid-specific antigen, and an idiotype/anti-idiotype reaction. Regardless of the cause, the common outcome is the production of 1 or more types of autoantibodies, which affect thyroid function positively or negatively.

Graves disease

Adams and colleagues described the concept of Graves disease as an autoimmune dysfunction of the thyroid gland. These investigators noted that the sera of patients with Graves disease contained a factor that stimulated the murine thyroid gland. This factor had a longer duration of action than that of thyrotropin (ie, thyroid-stimulating hormone [TSH]), the long-acting thyroid stimulator. ^{[4, 5, 6, 7]}

Further studies revealed that these long-acting thyroid stimulators are autoantibodies directed against the TSH receptor. The activating versions of the TSH receptor are the thyroid-stimulating autoantibodies, which activate adenylate cyclase and which stimulate thyroid function.

In terms of histologic features, the thyroid glands of patients with Graves disease show follicular hypertrophy and hyperplasia (see Histologic Findings).

Hashimoto thyroiditis

Hashimoto thyroiditis is also known as goitrous chronic thyroiditis. Almost all patients with this disease have positive test results for the thyroid peroxidase antibody (anti-TPO), an autoantibody against thyroid peroxidase enzyme. Of these patients, 50-70% also have positive results for antithyroglobulin antibodies.

Classic histologic findings of Hashimoto thyroiditis are extensive lymphocytic infiltration, follicular rupture, eosinophilia, various degrees of hyperplasia, and fibrosis (see Histologic Findings).

Atrophic chronic thyroiditis

Atrophic chronic thyroiditis is a rare autoimmune cause of hypothyroidism. This condition is characterized by the presence of blocking autoantibodies to the TSH receptors.

Postpartum thyroiditis

PPT is a variant of chronic autoimmune thyroiditis (Hashimoto thyroiditis). PTT is characterized by the presence of antimicrosomal antibodies. Histologic examination of PTT-affected thyroid glands affected reveals destructive lymphocytic thyroiditis (see Histologic Findings).

United States statistics

Hyperthyroidism affects 0.1-0.4% of pregnancies. Graves disease accounts for 85% of these cases. Hypothyroidism affects up to 2.2% of pregnant women and Hashimoto thyroiditis is the most common cause. Atrophic thyroiditis is less common. Postpartum thyroiditis has a prevalence ranging from 3.3-8.8% in the United States.

The most common cause of thyrotoxicosis in the postpartum period is postpartum thyroiditis. Specifically, the prevalence of postpartum thyrotoxicosis has been shown to be 4.1% vs 0.2% for thyrotoxicosis related to Graves disease.

International statistics

The reported range for the frequency of PPT is wide. In Thailand, as few as 2 in 100 postpartum women are affected. By comparison, some Canadian studies revealed a frequency of 2 per 10 postpartum women. These differences may be due to variations in diagnostic criteria, in genetic factors, and in iodine consumption. ^[8]

Sex- and age-related demographics

Autoimmune thyroid diseases occur more often in women than in men. The female-to-male ratio is 5-10:1. ^[9]

Autoimmune thyroid dysfunction most often affects women of reproductive age.

The outcome of pregnancies affected by autoimmune thyroid disease depends on the degree of metabolic control. Women with euthyroid disease can expect satisfactory outcomes of their pregnancy. With close follow-up postpartum, medical therapy can be adjusted to ensure a euthyroid state. This helps ensure a good prognosis.

Morbidity/mortality

Fetal and maternal outcomes improve when thyroid function returns to normal.

Hyperthyroidism

Uncontrolled hyperthyroidism, especially in the second half of pregnancy, can lead to numerous complications. Maternal complications include miscarriage, infection, preeclampsia, preterm delivery, congestive heart failure (CHF), thyroid storm, and placental abruption.

Fetal and neonatal complications include prematurity, small size for gestational age, intrauterine fetal death, fetal or neonatal goiter, and/or thyrotoxicosis. Overtreatment may cause iatrogenic fetal hypothyroidism. When maternal thyroid antibody titers are greater than 300% of the normal upper limit, the fetus is at risk of fetal hyperthyroidism and should be evaluated by ultrasound for evidence of hyper- or hypothyroidism. Fetal hyperthyroidism can include tachycardia, accelerated maturation of bone, goiter, growth restriction, and congestive heart failure. ^[10]

Hypothyroidism

Maternal complications of untreated hypothyroidism include microcytic anemia, preeclampsia, placental abruption, postpartum hemorrhage, cardiac dysfunction, and miscarriage. Fetal or neonatal complications include prematurity, low birth weight, congenital anomalies, stillbirth, and poor neuropsychological development. Abalovich et al showed about 60% risk of fetal loss with inadequate treatment or detection of hypothyroidism. ^[11]  Leung et al noted a 22% risk of gestational hypertension in pregnancy associated with hypothyroidism, compared to controls. ^[12]  Allan et al demonstrated an increased risk of fetal death with hypothyroidism. ^[13]

In particular, overt maternal hypothyroidism is associated with neonatal neurologic developmental delay because of the transplacental transfer of thyroid hormone in early pregnancy is inadequate. This process is required for brain development. The fetal thyroid does not begin to concentrate iodine until 10-12 weeks of gestation. Therefore, before this time, the mother must provide for all of the fetus' thyroxine (T4) requirements. Thus, the conclusion of all available evidence demonstrates that hypothyroidism is associated with significant adverse maternal and fetal sequelae.

Subclinical hypothyroidism may be associated with an increased risk of adverse pregnancy complications such as spontaneous abortions, fetal loss, and preterm labor. A study by Wilson et al found that women diagnosed with subclinical hypothyroidism during their pregnancy have an increased risk for severe preeclampsia. ^[14]  An association between maternal subclinical hypothyroidism and adverse fetal neurocognitive development is biologically plausible though not clearly demonstrated.

Approximately 10-15% of the population have thyroid antibodies, a number which may be even higher in the obstetric population ^[15] . These antibodies have been linked to an increased risk of spontaneous abortion.

It is debated whether isolated hypothyroxinemia causes any adverse effects on the developing fetus; reports of decreased IQ in offspring have been criticized for methodological processes and the plausibility of the conclusion.

Postpartum thyroiditis

Complications associated with postpartum thyroiditis (PPT) are maternal, and depression is common. Permanent hypothyroidism occurs in as many as 20-40% of women. ^[16]  These patients are also at high risk for recurrent PPT with subsequent pregnancies.

Complications

Hyperthyroidism

Uncontrolled hyperthyroidism, especially in the second half of pregnancy, can lead to numerous complications.

Maternal complications

• Miscarriage

• Infection

• Preeclampsia

• Preterm delivery

• Congestive heart failure

• Thyroid storm

• Placental abruption

Fetal and neonatal complications

• Prematurity

• Small size for gestational age

• Intrauterine fetal death

• Toxemia

• Fetal or neonatal thyrotoxicosis, including accelerated bone maturation, goiter, and hydrops

Hypothyroidism

Maternal complications of untreated hypothyroidism

• Microcytic anemia

• Preeclampsia

• Placental abruption

• Postpartum hemorrhage

• Cardiac dysfunction

• Miscarriage

Fetal or neonatal complications

• Prematurity

• Stillbirth

• Delayed bone maturation

• Goiter

• Hydrops

• Poor neurologic development

Postpartum thyroiditis

Complications associated with PPT are maternal, and depression is common. Permanent hypothyroidism may occur in as many as 30% of patients. These women are also at high risk for recurrent PPT after subsequent pregnancies.

The importance of compliance with medical therapy should be stressed. The need for frequent laboratory assessment should be discussed. The adverse effects of medical therapy, including the fetal risks, should be outlined.

For excellent patient education resources, visit eMedicineHealth's Thyroid and Metabolism Center. Also, see eMedicineHealth's patient education article Thyroid Problems.