Autoimmune Thyroid Disease and Pregnancy Workup

The American College of Obstetricians and Gynecologists (ACOG) does not recommend universal screening for thyroid disease in pregnant women. However, screening is warranted for those who are at increased risk. This includes pregnant persons who have a personal or family history of thyroid disease, type 1 diabetes mellitus, or symptoms suggestive of thyroid disease. There is no proven benefit in screening pregnant women with a mildly enlarged thyroid gland, whereas those with a significant goiter or distinct thyroid nodules require screening. ^[17]

Hyperthyroidism

• T3, T4, FT3, FT4, and TSH tests

  • Total T3 and total T4 levels are increased due to a rise in the amount of thyroid-binding globulin. Free T3 (FT3) and FT4 levels are high-normal in the first trimester and return to normal by the second trimester.

  • Total T4 values are not useful in pregnant women because they rise in response to the estrogen-induced increase in the amount of thyroid-binding globulin.

  • FT3 values should be measured when the TSH value is suppressed but the FT4 level is normal. An elevated T3 level confirms T3 toxicosis, an early stage in the development of true hyperthyroidism. ^[18]

  • TSH concentrations fall during pregnancy, especially in the first trimester, because hCG cross-reacts with TSH receptors on the thyroid gland.

    • In a prospective study of 666 women in Belgium, suppressed TSH levels were noted in 15%, 10%, and 5% in first-, second-, and third-trimester pregnancies. ^[19]

    • Trimester-specific TSH normograms have been described. TSH levels are significantly lower and FT4 levels are significantly higher in the first trimester than levels in the second or third trimesters.

    • Universal cut-off values are not recommended, nor are non-pregnant reference ranges. If possible, institutions should calculate their own reference ranges using pregnancy-specific values from the local population. The next best option is to adopt references ranges calculated from a non-local population with similar characteristics. ^[20]

    • If the above options for trimester-specific reference ranges for TSH are not available, the following reference ranges are recommended: first trimester, 0.1-2.5 mIU/L; second trimester, 0.2-3.0 mIU/L; third trimester, 0.3-3.0 mIU/L. ^[3]

  • TSH levels alone should not be used to diagnose hyperthyroidism in pregnancy.

  • The FT4 index is slightly low or normal.

  • The optimal method to assess serum FT4 during pregnancy is measurement of T4 in the dialysate or ultrafiltrate of serum samples employing on-line extraction/liquid chromatography/tandem mass spectometry (LC/MS/MS).

  • Among patients in a hyperthyroid state, the TSH level is low, whereas the FT4 or FT4 index value is elevated.

• Resin T3 update test: Resin T3 uptake is reduced because the number of unsaturated binding sites increases.

• Test for thyroid-stimulating immunoglobulins (TSIs)

  • Patients with Graves disease almost always have positive results for TSIs.

  • Measurement of TSI concentrations should be part of the workup for patients with hyperthyroidism. They should be assessed in the first trimester (or at the time of diagnosis) and, if elevated, again at 18-22 weeks and 30-34 weeks to inform decisions about fetal assessment. ^[18]  

• CBC, liver function test, and determination of calcium and magnesium levels

  • These laboratory tests should be ordered after hyperthyroidism is diagnosed.

  • Findings or conditions that can occur with hyperthyroidism include normochromic normocytic anemia, mild neutropenia, elevated liver enzyme levels, mild hypercalcemia, and hypomagnesemia.

• Antimicrosomal antibody test: Women who have positive results for antimicrosomal antibodies early in pregnancy or shortly after delivery are at risk for developing PPT.

Hypothyroidism

• FT4 and TSH tests: Definitions of hypothyroidism and subclinical hypothyroidism in pregnancy:

  • In primary hypothyroidism, TSH levels are elevated and the FT4 value or FT4 index should be low.

  • With suprathyroid hypothyroidism, the TSH level may be normal or low, and the FT4 level or FT4 index is low.

  • In subclinical hypothyroidism, the FT4 value is normal, and the TSH level is elevated.

  • Elevations in serum TSH during pregnancy should be defined using pregnancy-specific reference ranges.

  • Hypothyroidism is defined as an elevated TSH (>2.5 mIU/L) in conjunction with a decreased FT4 concentration.

  • Women with TSH levels of 10.0 mIU/L or above, regardless of their FT4 levels, are also considered to have hypothyroidism. ^{[3, 21]}

  • Subclinical hypothyroidism is defined as a serum TSH between 2.5 and 10 mIU/L with a normal FT4 concentration.

  • Isolated hypothyroxinemia is defined as a normal maternal TSH concentration in conjunction with FT4 concentrations in the lower 5th or 10th percentile of the reference range. ^[22]

• Tests for anti-TPO and antithyroglobulin antibodies

  • Levels of anti-TPO and antithyroglobulin antibodies should be measured in pregnant women with possible hypothyroidism to determine if Hashimoto thyroiditis is the cause.

  • Measurement of anti-TPO antibody concentrations is often sufficient because the results are almost always positive in patients with Hashimoto thyroiditis.

• CBC and liver function tests

  • Consider ordering a CBC and liver function tests after hypothyroidism is diagnosed.

  • Anemia is observed in as many as 30-40% of patients because erythropoiesis is decreased.

  • Concomitant vitamin B-12 or folic acid deficiency should be considered if the anemia is macrocytic.

  • Leukocyte and platelet counts are usually normal.

Postpartum thyroiditis

Generally, TSI is negative in PPT in the majority of cases, while it is positive with postpartum Graves disease. An elevated T4:T3 ratio suggests the presence of PPT. The radioiodine uptake is elevated or normal in Graves disease and low in PPT.

Imaging modalities currently available for the evaluation of thyroid disease are ultrasonography, CT scanning, MRI, and radioactive iodine uptake testing. Radioactive iodine uptake testing is contraindicated in pregnancy. Ultrasonography is considered a safe test in pregnancy, and sonographic findings can help in differentiating a cystic nodule from a solid nodule. Spectral Doppler ultrasound may be a useful adjunct to distinguish hyperthyroid and hypothyroid postpartum thyroiditis. ^[23]

Thyroid biopsy is rarely necessary for diagnosing autoimmune thyroid disease in pregnant women.

The workup of a thyroid nodule should not be delayed in pregnancy. Fine-needle aspiration biopsy can provide valuable cytologic information.

The essential histologic findings of Graves disease are glandular hyperplasia and hypertrophy characterized by increased height of the follicular cells and redundancy of the follicular wall. Lymphocytic infiltration reflects the immune aspect of this disease.

Ophthalmopathy of Graves disease is characterized by lymphocytic infiltration of the orbital contents with lymphocytes, mast cells, and plasma cells. Likewise, lymphocytic infiltration is readily observed in association with the dermal thickening seen in the dermopathy found in patients with Graves disease.

Hashimoto thyroiditis is characterized by extensive diffuse lymphocytic infiltration. Other classic findings are follicular rupture, eosinophilia, various degrees of hyperplasia, and fibrosis.

PPT is characterized by destructive lymphocytic infiltration of the thyroid gland.

See also Pathophysiology.