Thyroid function tests
The following tests are useful in selected situations.
Total thyroxine (T4)
The upper normal range is higher during pregnancy because of the increase in the levels of thyroxine-binding globulin (TBG). To ascertain the normal pregnancy range, the normal nonpregnant T4 level (5–12 μg/dL by most laboratories) should be multiplied by 1.5 to calculate the normal range for pregnancy (e.g. 7.5–18 μg/dL). This calculation will be more dependable until the problems associated with the free T4 immunoassays during pregnancy are resolved.
Free Thyroxine Index (FT4I)
Many commercial laboratories have discontinued offering the FT4I in favor of direct free T4 determinations by immunoassay which are more convenient in general practice outside pregnancy. If available, it will remain a useful test until the limitations of the freeT4 immunoassays during pregnancy are overcome.
Free thyroxine (FT4)
The levels of free T4 when measured by immunoassay have been shown to steadily decrease as pregnancy advances. These immunoassays are influenced by the changes in TBG and albumin levels that occur during pregnancy and are considered to be less reliable under conditions of altered protein binding. In addition, the normal reference ranges provided have been determined using nonpregnant individuals and are therefore not valid during pregnancy. At this time there is no consensus as to what the normal pregnancy levels should be for each trimester, which makes the usefulness of the current free T4 immunoassays limited. Trimester-specific reference intervals have been published using tandem mass spectrometry, a method that has been found to be accurate and reliable during pregnancy (first trimester: 1.13 ± 0.23 ng/dL, second trimester: 0.92 ± 0.30 ng/dL, third trimester: 0.86 ± 0.21 ng/dL [mean ± standard error]).
Total tri-iodothironine (T3)
The level of T3 is higher during pregnancy also due to increased levels of the thyroid hormone carrier proteins, mainly TBG and albumin. To calculate the normal pregnancy values, the nonpregnant reference levels are multiplied by 1.5 in the same manner described above to determine T4. Measuring T3 may be helpful when the serum thyroid-stimulating hormone (TSH) is suppressed but the total and/or free T4 levels are normal. An elevation in T3 is consistent with the diagnosis of T3 thyrotoxicosis, seen mainly in patients with hyperthyroidism caused by autonomous thyroid nodules and in the early phase of Graves’ disease. T3 is usually not elevated in the transient hyperthyroidism of hyperemesis gravidarum, and if elevated, usually not as high as in Graves’ disease or in toxic nodules.
Serum TSH
Serum TSH (ultrasensitive, at least third or fourth generation assays) is the best screening test for thyroid disease. However, during pregnancy TSH levels are influenced by the elevated concentration of human chorionic gonadotropin (hCG) and therefore, using the normal nonpregnant TSH levels will often lead to misdiagnosis. Several recent publications recommend the following trimester-specific reference values obtained from populations of normal pregnant women without thyroid antibodies: first trimester 0.10–2.5 μIU/L, second trimester 0.10–3 μIU/L, third trimester 0.13–3 μIU/L, although the first trimester normal lower limit has been reported to be as low as 0.03 μIU/L. An elevated value is diagnostic of hypothyroidism due to intrinsic thyroid disease. A suppressed or undetectable value is normally consistent with the diagnosis of hyperthyroidism. However, many women will be misdiagnosed, particularly during the first and second trimesters, if the general TSH reference values specified by the majority of laboratories (0.4–4.0 μIU/L) are used as the normal range for pregnancy.
Thyroid antibodies (thyroid peroxidase antibodies (TPO-Ab)) and antithyroglobulin antibodies (TG-Ab)
The presence of these antibodies in the serum is diagnostic of autoimmune thyroid disease and affected women are at risk of developing thyroid insufficiency as pregnancy progresses and for postpartum thyroiditis as well. They are most useful in the evaluation of goiter or hypothyroidism.
Serum thyroglobulin (Tg)
This test is used to monitor patients after treatment for thyroid carcinoma. It is an early marker for recurrence of the disease.
TSH receptor-binding antibodies (TSHR-Ab)
These antibodies are markers for Graves’ disease and include a group of immunoglobulins that compete with TSH for binding to its receptor. The currently commercially available tests report the percentage of inhibition of TSH binding to its receptor but do not specifically measure the antibodies’ ability to stimulate or inhibit the TSH receptor. To measure the specific stimulating receptor antibodies, it should be indicated that a thyroid-stimulating immunoglobulin (TSI) is the test desired. TSH receptor antibodies are present in up to 80% of women with present or past history of Graves’ disease. A significant elevation in maternal titer (>50%) may identify infants at risk for neonatal hyperthyroidism.
Transient hyperthyroidism of hyperemesis gravidarum
The symptoms of hyperemesis gravidarum include nausea and vomiting, greater than 5% weight loss, and large ketonuria. It is our experience that as many as 65% of patients with hyperemesis gravidarum also have at least one thyroid test in the hyperthyroid range (i.e. suppressed TSH, elevated T4 or, in 12% of cases, elevated T3). This is a self-limited abnormality and no specific antithyroid therapy is indicated although some authors have recommended treatment with antithyroid medication if there are clinical symptoms of overt hyperthyroidism and very high T4 and T3 concentrations, greater than 50% above the pregnancy-adjusted normal values. However, unnecessary treatment with antithyroid medications should be avoided unless there is evidence of Graves’ or a toxic nodule.
It may not be easy to differentiate the chemical hyperthyroidism of hyperemesis gravidarum from the hyperthyroidism of other causes. The following points may be helpful in the differential diagnosis: no history or symptoms of thyroid disease preceding pregnancy, negative family history, absence of goiter, negative thyroid antibodies, and symptom resolution and normalization of thyroid tests by 20 weeks in most cases.
Goiter is defined as an enlargement of the thyroid gland, which normally weighs between 15 and 25 g and in general is not palpable. In areas of normal dietary iodine ingestion, the thyroid gland enlarges during pregnancy, as shown by studies using serial sonography, but usually not enough to be detected clinically. Therefore, any enlargement noted by physical examination should be considered abnormal and deserving of careful evaluation, including a thyroid ultrasound. The physician should be able to describe the size, consistency, symmetry, and tenderness, along with the presence of nodularity or adenopathy. The determination of T4 and TSH levels will define the functional status of the goiter. The presence of thyroid antibodies is suggestive of autoimmune thyroid disease as the etiology of the goiter.
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