Clinical and Interpretive

TSH is used for screening for thyroid dysfunction and detecting mild (subclinical), as well as overt, primary hypo- or hyperthyroidism in ambulatory patients, monitoring patients on thyroid replacement therapy, confirmation of thyroid-stimulating hormone (TSH) suppression in thyroid cancer patients on thyroxine suppression therapy, and prediction of thyrotropin-releasing hormone-stimulated TSH response.

Thyroid-stimulating hormone (TSH, thyrotropin) is a glycoprotein hormone consisting of 2 subunits. The alpha subunit is similar to those of follicle-stimulating hormone, human chorionic gonadotropin, and luteinizing hormone. The beta subunit is different from those of the other glycoprotein hormones and confers its biochemical specificity. TSH is synthesized and secreted by the anterior pituitary in response to a negative feedback mechanism involving concentrations of free triiodothyronine and free thyroxine. Additionally, the hypothalamic tripeptide, thyrotropin-releasing hormone, directly stimulates TSH production.

TSH interacts with specific cell receptors on the thyroid cell surface and gives rise to 2 main actions. First, it stimulates cell reproduction and hypertrophy. Second, it stimulates the thyroid gland to synthesize and secrete triiodothyronine and thyroxine. Serum TSH concentrations exhibit a diurnal variation with the peak occurring during the night and the nadir occurring between 10 a.m. and 4 p.m. This biological variation does not influence the interpretation of the test result since most clinical TSH measurements are performed on ambulatory patients between 8 a.m. and 6 p.m.

When hypothalamic-pituitary function is normal, a log/linear inverse relationship between serum TSH and free thyroxine exists.

In primary hypothyroidism, thyroid-stimulating hormone (TSH) levels will be elevated. In primary hyperthyroidism, TSH levels will be low.

The ability to quantitate circulating levels of TSH is important in evaluating thyroid function. It is especially useful in the differential diagnosis of primary (thyroid) from secondary (pituitary) and tertiary (hypothalamus) hypothyroidism. In primary hypothyroidism, TSH levels are significantly elevated, while in secondary and tertiary hypothyroidism, TSH levels are low or normal.

Elevated or low TSH in the context of normal free thyroxine is often referred to as subclinical hypo- or hyperthyroidism, respectively.

Thyrotropin-releasing hormone (TRH) stimulation differentiates all types of hypothyroidism by observing the change in patient TSH levels in response to TRH. Typically, the TSH response to TRH stimulation is exaggerated in cases of primary hypothyroidism, absent in secondary hypothyroidism, and delayed in tertiary hypothyroidism. Most individuals with primary hyperthyroidism have TSH suppression and do not respond to TRH stimulation with an increase in TSH over their basal value.

Sick, hospitalized patients may have falsely low or transiently elevated TSH.In patients receiving therapy with high biotin doses (ie, >5 mg/day), no specimen should be taken until at least 8 hours after the last biotin administration.

For assays employing antibodies, the possibility exists for interference by human antianimal antibodies (ie, heterophile antibodies) in the patient specimen. Patients who have been regularly exposed to animals or have received immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies, eg, human antimouse antibodies, that interfere with immunoassays. This may falsely elevate or falsely decrease the results.

Interference due to extremely high titers of antibodies to analyte-specific antibodies, streptavidin or ruthenium can occur.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.