Thyroid function tests (TFTs) are the most commonly used endocrine test.American Thyroid Association: thyroid function tests Thyroid hormones thyroxine (T4) and triiodothyronine (T3) are produced, stored, and secreted by the thyroid gland. These hormones, particularly T3, play a major role in multiple biologic and metabolic processes. They act by binding to thyroid receptors that are distributed in almost every organ. Typically, this process regulates gene transcription and the subsequent production of various proteins that are involved in development, growth, and cellular metabolism.[1] This topic discusses indications for TFTs and the interpretation of results, in particular serum thyrotropin (TSH) levels and associated free T3 and free T4 levels.
Overview
Introduction
Thyroid hormone production
Thyroid hormone production is regulated by the hypothalamus and pituitary gland. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates pituitary TSH synthesis and secretion. In turn, TSH stimulates production and release of T4 and T3 from the thyroid gland. Once released, T4 and T3 exert a negative feedback mechanism on the production of TRH and TSH.[1]
The protein thyroglobulin (Tg) is produced and used by the thyroid gland to produce T4 and T3. T3 is the biologically active form of thyroid hormone whereas T4 is considered a prohormone to T3. The thyroid gland produces 100% of circulating T4 but only 20% of circulating T3. The remaining 80% of T3 is produced by the conversion of T4 to T3 in the peripheral tissues. Acute illnesses, as well as certain drugs, may inhibit the process of converting T4 to T3 and, therefore, affect their serum levels.
Thyroid hormone-binding proteins
T3 and T4 circulate in peripheral blood bound to proteins (thyroxine-binding globulin [TBG], transthyretin [previously prealbumin], and albumin). Over 99% of T4 and T3 are protein-bound. Only the unbound or "free" portion, free T3 (FT3) and free T4 (FT4), are active. Therefore, any changes in the quantity or quality of thyroid-binding proteins will produce changes in circulating thyroid hormone levels.[2]
Indications for TFTs: general considerations
According to population studies in the US and the UK, the prevalence of overt hypothyroidism varies from 0.1% to 2%, and of subclinical hypothyroidism from 4% to 10% of adults. Incidence is higher in women than in men.[3] [4] The overall prevalence of thyroid disease varies widely based on population. In the US, the prevalence of hyperthyroidism is approximately 1.2% (0.5% overt and 0.7% subclinical); the most common causes include Graves disease, toxic multinodular goiter, toxic adenoma, and excess thyroid hormone ingestion.[3] [5]
In the US, the American Thyroid Association guidance on thyroid dysfunction suggested that all adults should have serum TSH concentration measured at 35 years of age and every 5 years thereafter.[6] The American Association of Clinical Endocrinologists is also in favor of screening in "older people" (age not specified), especially women.[7] However, the US Preventive Services Task Force found that evidence was insufficient to recommend for or against routine screening for thyroid disease in adults.[8] In the UK, Canada, and Australasia, the healthy adult population is not routinely screened for thyroid disease.[9] [10] [11] [12]
Screening may be appropriate in people at higher risk of developing thyroid dysfunction. For example, people with Down syndrome are more frequently affected by both hypothyroidism and hyperthyroidism, and the symptoms may be masked by their diagnosis. The Down syndrome Medical Interest Group (DSMIG) therefore recommends screening all infants with Down syndrome at ages 4-6 months, at ages 12 months and annually thereafter.[13]
- With a goiter
- Who have had surgery or radiation therapy affecting the thyroid gland
- Who have pituitary or hypothalamic disease, surgery, or irradiation
- With diabetes mellitus type 1
- With Addison disease
- With first-degree relative with autoimmune thyroid disease
- With vitiligo
- With pernicious anemia
- With leukotrichia (prematurely gray hair)
- With psychiatric disorders
- With Turner syndrome
- Receiving certain medications and iodine-containing compounds (e.g., amiodarone, radiocontrast agents, expectorants containing potassium iodide, kelp, interferon alfa, and tyrosine-kinase inhibitors, most notably sunitinib).
TSH measurement is also recommended before starting certain treatments that can affect thyroid function. This includes immune reconstitution therapy (e.g., alemtuzumab treatment for multiple sclerosis, antiretroviral therapy for HIV infected patients, allogeneic bone marrow transplantation, or hematopoietic stem cell transplantation), and treatment with immune checkpoint inhibitors.[18] [19] [20]
Known thyroid dysfunction and preconception
In patients with known history of hypothyroidism who are trying to conceive, thyroxine levels should be increased to achieve serum TSH values to <2.5 mIU/mL. This increase will reduce the risk of TSH elevation during the first trimester.[21]
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Hypothalamic-pituitary-thyroid axis
Differentiating causes of low TSH and high free T4 (FT4) and/or free T3 (FT3)
Differentiating causes of low TSH and low free T4 (FT4) and/or free T3 (FT3)
Differentiating causes of low TSH and normal free T4 (FT4) and/or free T3 (FT3)
Differentiating causes of high TSH and high free T4 (FT4) and/or free T3 (FT3)
Differentiating causes of high TSH and low free T4 (FT4) and/or free T3 (FT3)
Differentiating causes of high TSH and normal free T4 (FT4) and/or free T3 (FT3)
Differentiating causes of normal TSH and low free T4 (FT4) and/or free T3 (FT3)
Drug effects on the thyroid
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