Your patient may have thyroid function tests ordered. Although you may see this often, why are these tests ordered and what are they measuring? To better understand the ins and outs of thyroid function testing, let's start with a brief review of thyroid gland physiology.

The metabolic regulator

Located in front of the neck, below the larynx, the butterfly-shaped thyroid gland is an endocrine gland that produces thyroid hormone (see Picturing the thyroid gland). Thyroid hormone regulates the body's metabolism, promotes skeletal growth and brain development, stimulates the heart, and regulates energy production. It's composed of two types of cells: follicular cells, which secrete the thyroid hormones triiodothyronine (T₃) and thyroxine (T₄), and parafollicular cells, which produce calcitonin to control calcium function.

Central to the production of T₃ and T₄ is a complex relationship between the secretion of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH). A classic negative feedback loop driven by T₄ serum concentrations modulates the secretion of both TRH and TSH (see The hypothalamic-pituitary-thyroid axis). First, the hypothalamus sends TRH to the pituitary gland. Then, the pituitary gland responds by secreting TSH. When the thyroid gland receives the pituitary gland's signal in the form of TSH, it responds by producing T₃ and T₄. Completing the cycle, thyroid hormone then signals the pituitary gland to lower secretion of TSH. TSH has a diurnal pattern: The lowest levels are in midafternoon, with peak levels in the evening. Although this may sound rather complicated, an endocrinologist relies strongly on serum values obtained from these hormones to determine if an endocrine disorder originates from pituitary or hypothalamic tissue or from the thyroid gland itself.

T₃ and T₄ circulate in the blood by reversibly binding to the carrier proteins thyroxine-binding globulin, albumin, and prealbumin. Over 99% of both hormones are bound to proteins, and it's important to note that only the free, or unbound, hormone is metabolically active. For example, T₄ circulates in the blood in two forms: T₄ bound to proteins that prevent it from entering various tissues and free T₄, which enters target tissues.

Thyroid hormone synthesis requires iodine and, once formed, T₃ and T₄ are stored within thyroglobulin in the lumen of the thyroid follicle until release. The hormones are liberated by the action of TSH. Because TSH also regulates the uptake and organification of iodide, it's key in thyroid hormone regulation.

Who should be tested?

The American Thyroid Association recommends screening at age 35 and every 5 years after, if initial screening results are normal. Closer attention to thyroid monitoring must be given to high-risk patients, including newborns, women over age 60, patients who've undergone neck irradiation, and those with autoimmune diseases, particularly type 1 diabetes.

During pregnancy, women may develop hypothyroidism or hyperthyroidism, which increases the risk of miscarriage, premature birth, and preeclampsia. In addition, children of hypothyroid mothers are at risk for impaired intelligence and developmental problems. That's why many healthcare providers choose to measure TSH at the first prenatal visit to assess thyroid functioning. The American Association of Clinical Endocrinologists recommends TSH measurements for all women considering pregnancy or during the first trimester. However, many medical societies recommend testing only high-risk women.

Patients taking certain drugs, such as amiodarone or lithium, require thyroid function testing as well. Amiodarone is an antiarrhythmic drug that can cause hypothyroidism or hyperthyroidism. It inhibits peripheral conversion of T₄ to T₃ in the tissue. It also contains high levels of iodine, which may contribute to a thyroid disorder. Amiodarone carries a black-box warning: It must be used under close medical supervision and is usually started in the hospital. Thyroid function must be monitored before and periodically during treatment, particularly in older patients or any patient with a history of thyroid nodules, goiter, or other thyroid dysfunction. Lithium, a medication used to treat bipolar disorder, may reduce the insertion of iodine into thyroid hormone. It can inhibit thyroid hormone secretion, resulting in goiter and hypothyroidism. For this reason, TSH, T₃, and T₄ levels should be measured before treatment and yearly for patients who are prescribed lithium.

Testing TSH, T

TSH (also known as thyrotropin) testing measures thyroid-stimulating hormone levels in the blood. The FDA recently approved a test that detects elevated TSH levels in 10 minutes employing the finger-stick technique. The gold standard for evaluating thyroid function, it's highly sensitive and specific. TSH is a sensitive measure of hypothyroidism because even a small reduction in serum T₃ and T₄ can result in a dramatic rise in serum TSH. The reference range for TSH is 0.4 to 4.0 mIU/L in adults; however, various labs may yield slightly different ranges.

T₃ testing may be used to measure total (bound plus free) or free T₃. Normal total T₃ levels in adults range from 100 to 200 ng/dL; free T₃ ranges from 260 to 480 pg/dL. As with T₃ testing, T₄ may be measured using the total or free values. Normal total T₄ levels in adults range from 4.5 to 11.2 µg/dL; free T₄ ranges from 0.9 to 1.7 ng/dL. Measurement of free T₄ is the most important in determining how the thyroid is functioning. Free T₄ is measured routinely to assess thyroid gland function and monitor thyroid replacement therapy consisting of T₄, such as levothyroxine. Among patients who are newly diagnosed with hyperthyroidism, this test more accurately reflects thyroid status than serum TSH.

Other thyroid function tests

When thyroid gland inflammation or other genetic conditions exist, the immune system directs plasma cells to manufacture antibodies. The result is a protein that destroys thyroid tissue or interferes with thyroid hormone synthesis. Antibodies may be developed that act against thyroid epithelial cells, enzymes, receptors, and globulins. When present, thyroid peroxidase antibody, thyroglobulin antibody, and TSH receptor antibody may indicate a hyperthyroid condition called Graves' disease. Under normal conditions, antibodies directed against thyroid function shouldn't be detected in the serum.

A radioactive iodine scan using I¹²³ tests the rate at which the thyroid gland absorbs and metabolizes iodine. Scans are essentially pictures of the thyroid and glandular activity. Radioactive iodine is given orally or I.V.; 24 hours later, the thyroid gland is scanned having taken up the tracer iodine. An uptake of greater than 35% means that the thyroid gland is producing too much T₄, which may indicate Graves' disease, multinodular goiter, or a toxic adenoma. A low uptake may reflect the effects of amiodarone, excess levothyroxine administration, or thyroiditis. Radioactive iodine uptake and thyroid scanning aren't useful in detecting hypothyroidism because these tests require some level of endogenous function to provide information.

Thyroid nodules are often found incidentally during a physical exam or radiographic test. They're present in patients who have normal thyroid function or those who have hypothyroid or hyperthyroid activity. To evaluate suspicious nodules, a minimally invasive test called a fine-needle aspiration is performed. Questionable nodules are those that are larger than 1 cm in diameter, those that contain microcalcifications, or those that have irregular margins. The majority of thyroid nodules are benign, but 5% to 6% of solitary nodules are malignant.

What you need to do

If TSH, T₃, or T₄ testing is ordered for your patient, explain to her that blood will be drawn from a vein, usually from the inside of the elbow or back of the hand. It's then collected into an airtight vial or tube attached to the needle. Ask her whether she has taken medications or agents that contain iodine because these may alter test results. Iodine-containing medications include contrast agents and those used to treat thyroid disorders. Less obvious sources of iodine include topical anesthetics, multivitamin preparations, and food supplements commonly found in health food stores.

Other medications that may affect test results include estrogen, salicylates, amphetamines, chemotherapeutic agents, antibiotics, corticosteroids, and mercurial diuretics. For a list of some of the medications that may affect results, see Medications that may alter thyroid test results.

After the results of thyroid testing are known, it's important to review the care plan related to achieving a euthyroid state. The goal is to attain a balance of thyroid function, and your patient must understand that it may take several weeks for medication to produce results and for symptoms to subside.

Know the routine

Thyroid screening is routinely performed and you'll encounter many individuals who require testing. Knowledge of the basics of thyroid function will aid you in recognizing when your patient needs intervention.

Thyroid test values and interpretations

Medications that may alter thyroid test results

Learn more about it

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