Tests of Thyroid Function
Detection of thyroid disease and evaluation of the efficacy of therapy require the use of various combinations of laboratory tests. The American Thyroid Association recommends initial screening with tests of TSH and free T4.
Measurement of serum TSH
Thyroid-stimulating hormone secretion by the pituitary is tightly controlled by negative-feedback mechanisms regulated by serum T4 and T3 levels. TSH levels begin to rise early in the course of hypothyroidism and fall in hyperthyroidism, even before free T4 levels are outside the reference range. Therefore, the serum TSH level is a sensitive indicator of thyroid dysfunction.
Some extremely sensitive assays of TSH can detect levels down to 0.005 mIU/L, making it possible to differentiate low normal values from abnormally low values. The TSH test is useful for (1) screening for thyroid disease, (2) monitoring replacement therapy in hypothyroid patients (TSH levels respond 6–8 weeks after changes in hormone replacement dosage), and (3) monitoring suppressive therapy for thyroid nodules or cancer. In screening for thyroid disease, the combination of free T4 and sensitive TSH assays has a sensitivity of 99.5% and a specificity of 98.0%. As a result, both of these tests are used together for screening in most situations. There is presently some controversy about the upper limit of normal for TSH, so endocrinologic consultation is indicated in borderline cases.
Measurement of serum T4
Total serum T4 comprises 2 parts: the protein-bound fraction and the free hormone. Total T4 levels can be affected by changes in serum TBG levels, while euthyroidism is maintained and free T4 levels remain normal. Levels of TBG and total T4 are elevated during pregnancy and with use of oral contraceptives, while free T4 levels remain normal. Low TBG and total T4 levels are associated with chronic illness, protein malnutrition, hepatic failure, and use of glucocorticoids.
Measurement of serum T3
Serum T3 levels may not accurately reflect thyroid gland function for 2 reasons: first, T3 is not the major secretory product of the thyroid; and, second, many factors influence T3 levels, including nutrition, medications, and mechanisms regulating the enzymes that convert T4 to T3. Determination of T3 levels is indicated in patients who may have T3 thyrotoxicosis, an uncommon condition in which clinically hyperthyroid patients have normal T4 and free T4 but elevated T3 levels.
Thyroid hormone–binding protein tests
Radioactive iodine uptake testing can be used to distinguish Graves disease from other causes of hyperthyroidism in the absence of other clinical features of Graves disease. However, it is not routinely performed.
Thyroid antibody tests
Several antibodies against thyroid antigens can be detected in the blood. The most common is thyroid peroxidase antibody, which has 99% sensitivity and specificity for Graves disease. Antibodies to thyroglobulin are also found in various thyroid diseases, including Hashimoto thyroiditis, Graves disease, and thyroid carcinoma. Patients with Graves disease usually have antibodies called thyroid-stimulating immunoglobulins (TSIs), which are directed at TSH receptors. These antibodies generally stimulate the release of thyroid hormone, but in rare cases patients have antibodies that block thyroid hormone release. High serum levels of TSI and the absence of thyroperoxidase antibody are both risk factors for ophthalmopathy in patients with Graves disease.
Thyroid scanning is useful in distinguishing functioning from nonfunctioning thyroid nodules and in evaluating chest and neck masses for metastatic thyroid cancer.
Ultrasonography, which can detect nodules as small as 1 mm, is used to identify the presence of cystic or solid thyroid nodules.
Biopsy to obtain tissue samples for evaluating thyroid nodules may be performed with fine-needle aspiration, core, or excisional techniques. Fine-needle aspiration specimens require interpretation by an experienced cytologist.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.