Thyroid Disease in Pregnancy

Thyroid disease is common in pregnancy. The thyroid gland undergoes several changes that complicate testing during pregnancy; these changes can result in elevated thyroxine (T4)-binding globulin, total T4, total triiodothyronine (T3), and serum thyroglobulin (Tg) concentrations and elevated renal iodine clearance, as well as low thyroid-stimulating hormone (TSH, or thyrotropin) and serum free T4 concentrations. Concentrations of these analytes may vary between trimesters. As a result, reference intervals for thyroid tests must be adjusted during pregnancy to accurately identify thyroid disease, which is essential to avoid adverse outcomes of thyrotoxicosis and hypothyroidism. Commonly used tests include blood tests for TSH and thyroid hormones, as well as autoantibody testing to assess thyroid autoimmunity.

Quick Answers for Clinicians

Who should be screened for thyroid disease in pregnancy?

Universal screening for hypothyroidism (including subclinical hypothyroidism) in pregnancy is not recommended by most organizations. Instead, multiple professional organizations recommend aggressive case finding in individuals at risk for thyroid disease.

What is the appropriate reference interval for thyroid-stimulating hormone in pregnancy?

Thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) concentrations in pregnancy are different from those in nonpregnant adults and vary by trimester. Due to these physiologic variations, pregnancy- and trimester-specific reference intervals for TSH should be used. Laboratory-specific TSH reference intervals are also recommended, given that considerable variation may exist between populations. If such intervals are not available, published pregnancy-specific TSH reference intervals (“transferable” reference intervals) from similar populations should be used. Finally, method-specific reference intervals should be used because variation may exist between assays.

Should the free thyroxine (T4) index be used in pregnancy?

The use of the free thyroxine (T4) index is somewhat controversial. Although some professional societies still support use of the free T4 index, direct measurement of free T4 (eg, via equilibrium dialysis and mass spectrometry with liquid chromatography [LC-MS/MS]) is preferred during pregnancy and should be performed when available. Modern immunoassay results have also demonstrated good correlation with free T4 concentrations as measured by LC-MS/MS; such immunoassays can be used as long as method-specific reference intervals are applied.

How can thyroid test results help distinguish patients with euthyroid sick syndrome in late pregnancy?

In late pregnancy, free thyroxine (T4) and free triiodothyronine (T3) concentrations are low, and the thyroid-stimulating hormone (TSH) concentration is normal. These same laboratory results are typical of patients with euthyroid sick syndrome. A distinguishing feature in patients with euthyroid sick syndrome, however, is that total T3 and T4 concentrations will be low in late pregnancy; in a normal late pregnancy, total T3 and T4 concentrations would be elevated.

Indications for Testing

Laboratory testing may be used to screen for and diagnose thyroid disease in women at high risk for thyroid disease who are pregnant or plan to become pregnant. Laboratory testing may also be used to monitor the progression of disease and guide the administration of thyroid medication during pregnancy.

Screening

In general, testing is not recommended for asymptomatic women who are not at increased risk for thyroid disease; aggressive case finding in individuals at high risk for thyroid disease may be a suitable alternative. Testing for subclinical hypothyroidism is not recommended.

Laboratory Testing

Recommendations for laboratory testing for thyroid disease in pregnancy vary by society. This ARUP Consult topic provides an overview. For detailed recommendations, see guidelines from:

Diagnosis of Thyroid Disease in Pregnancy

Thyroid Function Tests

Thyroid function testing during pregnancy is complicated by physiologic variations in hormone concentrations, and trimester-specific reference intervals should be used. Population-specific reference intervals are also recommended, as is consideration of assay-specific intervals. See Quick Answers for Clinicians for additional information.

TSH testing is the first step in the evaluation of thyroid disease in all individuals, including pregnant women. ACOG recommends free T4 measurement if TSH values are outside of trimester-specific reference intervals. Free T3 testing is recommended in pregnant women with low TSH, normal free T4 concentrations, and strong clinical suspicion for overt hyperthyroidism.

Expected Thyroid Hormone Concentrations in Thyroid Disease During Pregnancy
	TSH^a	Free T4^b	Free T3
Normal pregnancy	Trimester and assay specific	Trimester and assay specific	Normal
Overt hypothyroidism	High	Low	Not informative
Hashimoto disease (majority of overt hypothyroidism cases in pregnancy)	High	Low	Not informative
Subclinical hypothyroidism	High	Normal	Not informative
Overt hyperthyroidism	Low	High	High
Graves disease (95% of overt hyperthyroidism cases in pregnancy)	Low	High	High
Subclinical hyperthyroidism	Low	Normal	Normal
T3 toxicosis	Low	Normal	High
Hyperemesis gravidarum	Low	High	High
^aTSH reference intervals should be assay, population, and trimester specific. The following trimester-specific values may be used if more suitable reference intervals are not available: 0.1-4 mIU/L (first trimester), 0.2-4 mIU/L (second trimester), and 0.3-4 mIU/L (third trimester). ^bTotal T4 may be more accurate than free T4 in certain circumstances. Sources: Alexander, 2017; ACOG, 2015

Autoantibody Tests

The ATA recommends that thyroid peroxidase autoantibody (TPOAb) status be assessed in all pregnant women with TSH concentrations >2.5 mIU/L. Tests for TPOAb and other autoantibodies may be useful for distinguishing autoimmune thyroiditis from other etiologies of thyroid disease. For information on autoantibody testing in pregnant and nonpregnant individuals with thyroid disease, see the ARUP Consult Autoimmune Thyroiditis topic.

Other Tests and Procedures

Radioactive iodine testing is not recommended in pregnant individuals. Ultrasound can be used as a safe and cost-effective alternative during pregnancy and lactation.

Fine needle aspiration (FNA) of thyroid nodules is used to investigate potential infectious or cancerous causes of thyroid disease in pregnant and nonpregnant adults. For additional information on testing for thyroid cancer, see the ARUP Consult Thyroid Cancer topic.

Monitoring

TSH measurement is the recommended initial test and should be performed as soon as possible after conception in women with overt hypothyroidism who are being treated with levothyroxine. In pregnant women with hyperthyroidism who are being treated with thioamide drugs, regular monitoring using free T4 testing is recommended. Regular monitoring is also recommended in pregnant women with known thyroid autoimmunity. Women with overt or subclinical hypothyroidism or who are at risk for hypothyroidism (eg, patients with a positive TPOAb or TgAb test), irrespective of treatment status, should have serum TSH measured every 4 weeks through the middle of pregnancy, and at least once at approximately 30 weeks of gestation.

Testing for Postpartum Thyroiditis

Recommendations for postpartum thyroiditis testing vary by society. There is insufficient evidence to recommend universal screening for postpartum thyroiditis. Testing is recommended in symptomatic women and in women at high risk (eg, with a history of postpartum thyroiditis). The ATA recommends screening for hypothyroidism in all women with depression or postpartum depression. Postpartum thyroiditis can be distinguished from Graves disease by the ratio of free T3 to free T4; the ratio will be lower in patients with postpartum thyroiditis.

Fetal Testing

In general, laboratory evaluation of fetal thyroid function is not recommended. In cases of maternal hyperthyroidism, however, fetal evaluation may be appropriate due to the severity of the consequences of fetal thyroid disease. Antenatal diagnostic testing is also recommended if a fetal goiter is discovered during ultrasound and there is a family history of genetically linked dyshormonogenesis. The mainstays of fetal assessment are ultrasound and clinical exam; laboratory testing (TSH and free T4) using cord blood is recommended only if needed to exclude the diagnosis of fetal thyroid disease or if intervention is being considered. If the fetal hyperthyroidism diagnosis presents a potential danger to the pregnancy, frequent clinical, laboratory, and ultrasound monitoring is recommended.