THYROID FUNCTION AND DYSFUNCTION
Various hormones and chemicals are responsible for normal thy-roid function. Key among them are thyroid hormone, calcitonin, and iodine.
The two separate hormones, thyroxine (T4) and triiodothyronine (T3), that are produced by the thyroid gland and that make up thy-roid hormone, are amino acids that have the unique property of containing iodine molecules bound to the amino acid structure. T4 contains four iodine atoms in each molecule, and T3 contains only three. These hormones are synthesized and stored bound to proteins in the cells of the thyroid gland until needed for release into the bloodstream. About 75% of bound thyroid hormone is bound to thyroxine-binding globulin (TBG); the remaining bound thyroid hormone is bound to thyroid-binding prealbumin and albumin.
Iodine is essential to the thyroid gland for synthesis of its hormones. In fact, the major use of iodine in the body is by the thyroid, and the major derangement in iodine deficiency is alteration of thyroid function. Iodide is ingested in the diet and absorbed into the blood in the gastrointestinal tract. The thyroid gland is extremely efficient in taking up iodide from the blood and concentrating it within the cells, where iodide ions are converted to iodine molecules, which react with tyrosine (an amino acid) to form the thyroid hormones.
The secretion of T3 and T4 by the thyroid gland is controlled by thyroid-stimulating hormone (TSH, or thyrotropin) from the an-terior pituitary gland. TSH controls the rate of thyroid hormone release. In turn, the level of thyroid hormone in the blood determines the release of TSH. If thyroid hormone concentration in the blood decreases, the release of TSH increases, which causes increased out-put of T3 and T4. This is an example of negative feedback.
Thyrotropin-releasing hormone (TRH), secreted by the hypo-thalamus, exerts a modulating influence on the release of TSH from the pituitary. Environmental factors, such as a decrease in temperature, may lead to increased secretion of TRH, resulting in elevated secretion of thyroid hormones. Figure 42-4 shows the hypothalamic-pituitary-thyroid axis, which regulates thyroid hor-mone production.
The primary function of the thyroid hormone is to control the cellular metabolic activity. T4, a relatively weak hormone, main-tains body metabolism in a steady state. T3 is about five times as potent as T4 and has a more rapid metabolic action. These hor-mones accelerate metabolic processes by increasing the level of specific enzymes that contribute to oxygen consumption and al-tering the responsiveness of tissues to other hormones. The thy-roid hormones influence cell replication and are important in brain development. Thyroid hormone is also necessary for nor-mal growth. The thyroid hormones, through their widespread ef-fects on cellular metabolism, influence every major organ system.
Calcitonin, or thyrocalcitonin, is another important hormone se-creted by the thyroid gland. It is secreted in response to high plasma levels of calcium, and it reduces the plasma level of cal-cium by increasing its deposition in bone.
The thyroid gland is inspected and palpated routinely on all pa-tients. Inspection begins with identification of landmarks. The lower neck region between the sternocleidomastoid muscles is in-spected for swelling or asymmetry. The patient is instructed to extend the neck slightly and swallow. Thyroid tissue rises nor-mally with swallowing. The thyroid is then palpated for size, shape, consistency, symmetry, and the presence of tenderness.
The examiner may examine the thyroid from an anterior or a posterior position. In the posterior position, both hands encircle the patient’s neck. The thumbs rest on the nape of the neck, while the index and middle fingers palpate for the thyroid isthmus and the anterior surfaces of the lateral lobes. When palpable, the isthmus is perceived as firm and of a rubber-band consistency.
The left lobe is examined by positioning the patient so that the neck flexes slightly forward and to the left. The thyroid cartilage is then displaced to the left with the fingers of the right hand. This maneuver displaces the left lobe deep into the sternocleidomastoid muscle, where it can be more easily palpated. The left lobe is then palpated by placing the left thumb deep into the posterior area of the sternocleidomastoid muscle, while the index and middle fingers exert opposite pressure in the anterior portion of the muscle. Hav-ing the patient swallow during the maneuver may assist the exam-iner to locate the thyroid as it ascends in the neck. The procedure is reversed to examine the right lobe. The isthmus is the only por-tion of the thyroid that is normally palpable. If a patient has a very thin neck, two thin, smooth, nontender lobes may also be palpable.
If palpation discloses an enlarged thyroid gland, both lobes are auscultated using the diaphragm of the stethoscope. Auscultation identifies the localized audible vibration of a bruit. This abnor-mal finding indicates increased blood flow through the thyroid gland and necessitates referral to a physician. Tenderness, en-largement, and nodularity within the thyroid also require refer-ral for additional evaluation (Table 42-2).
Assessment measures in addition to palpation and auscultation include thyroid function tests, such as laboratory measurement of thyroid hormones, thyroid scanning, biopsy, and ultrasonog-raphy. The most widely used tests are serum immunoassay for TSH and free thyroxine (FT4). Measurement of TSH has a sen-sitivity and specificity of greater than 95% (Larson, Anderson & Koslawy, 2000). FT4 levels correlate with metabolic status and are elevated in hyperthyroidism and decreased in hypothyroidism.
Measurement of the serum TSH concentration is the single best screening test of thyroid function in outpatients because of its high sensitivity. The ability to detect minute changes in serum TSH makes it possible to distinguish subclinical thyroid disease from euthyroid states in patients with low or high normal values. Val-ues above the normal range of 0.4 to 6.15 μU/mL indicate pri-mary hypothyroidism, and low values indicate hyperthyroidism. When the TSH is normal, there is a 98% chance that the FT4 is also normal. Measurement of TSH is also used for monitoring thyroid hormone replacement therapy and for differentiating be-tween disorders of the thyroid gland itself and disorders of the pituitary or hypothalamus. Current recommendations suggest TSH screening for all adults beginning at age 35, and every 5 years thereafter (Ladenson, Singer, Ain, et al., 2000).
The test most commonly used to confirm an abnormal TSH is FT4. FT4 is a direct measurement of free (unbound) thyroxine, the only metabolically active fraction of T4. The range of FT4 in serum is normally 0.9 to 1.7 ng/dL (11.5 to 21.8 pmol/L). When measured by the dialysis method, FT4 is not affected by variations in protein binding and is the procedure of choice for following the changes in T4 secretion during treatment of hyperthyroidism. Measurement of FT4 by the immunoassay technique is less reli-able because it may be affected by medication, illness, or changes
in protein binding. An estimate (or index) of FT4 can also be cal-culated by multiplying total T4 by T3 resin uptake.
Measurement of total T3 or T4 includes protein-bound and free hormone levels that occur in response to TSH secretion. T4 is 80% bound to thyroxine-binding globulin (TBG); T3 is bound less firmly. Only 0.03% of T4 and 0.3% of T3 is unbound. Any factor that alters binding proteins also changes the T3 and T4 lev-els. Serious systemic illnesses, medications (eg, oral contracep-tives, corticosteroids, phenytoin, salicylates), and protein wasting as a result of nephrosis and use of androgens may interfere with accurate test results. Normal range for T4 is 4.5 to 11.5 μg/dL (58.5 to 150 nmol/L). Although serum T3 and T4 levels generally increase or decrease together, the T3 level appears to be a more ac-curate indicator of hyperthyroidism, which causes a greater rise in T3 than T4 levels. The normal range for serum T3 is 70 to 220 ng/dL (1.15 to 3.10 nmol/L).
The T3 resin uptake test is an indirect measure of unsaturated TBG. Its purpose is to determine the amount of thyroid hormone bound to TBG and the number of available binding sites. This provides an index of the amount of thyroid hormone already pre-sent in the circulation. Normally, TBG is not fully saturated with thyroid hormone, and additional binding sites are available to combine with radioiodine-labeled T3 added to the blood speci-men. The normal T3 uptake value is 25% to 35% (relative uptake fraction, 0.25 to 0.35), which indicates that about one third of the available sites of TBG are occupied by thyroid hormone. If the number of free or unoccupied binding sites is low, as in hyperthyroidism, the T3 uptake is greater than 35% (0.35). If the number of available sites is high, as occurs in hypothyroidism, the test results are less than 25% (0.25).
T3 uptake is useful in the evaluation of thyroid hormone levels in patients who have received diagnostic or therapeutic doses of iodine. The test results may be altered by the use of estrogens, an-drogens, salicylates, phenytoin, anticoagulants, or corticosteroids.
Autoimmune thyroid diseases include both hypothyroid and hyperthyroid conditions. Results of testing by immunoassay tech-niques for antithyroid antibodies, specifically antimicrosomal antibodies, are positive in chronic autoimmune thyroid disease (90%), Hashimoto’s thyroiditis (100%), Graves’ disease (80%), and other organ-specific autoimmune disease, such as lupus ery-thematosus and rheumatoid arthritis. Antithyroid antibody titers are normally present in 5% to 10% of the population and in-crease with age.
The radioactive iodine uptake test measures the rate of iodine up-take by the thyroid gland. The patient is administered a tracer dose of iodine-123 (123I) or another radionuclide, and a count is made over the thyroid gland with use of a scintillation counter, which detects and counts the gamma rays released from the breakdown of 123I in the thyroid. It measures the proportion of the adminis-tered dose present in the thyroid gland at a specific time after its administration. It is a simple test and provides reliable results. It is affected by the patient’s intake of iodide or thyroid hormone; therefore, a careful preliminary clinical history is essential in eval-uating results. Normal values vary from one geographic region to another and with the intake of iodine. Patients with hyper-thyroidism exhibit a high uptake of the 123I (in some patients, up to 90%), whereas patients with hypothyroidism exhibit a very low uptake. This test is also used to determine what dose of 123I should be administered to treat a patient with hyperthyroidism.
Using a small-gauge needle to sample the thyroid tissue for biopsy is a safe and accurate method of detecting malignancy. It is often the initial test for evaluation of thyroid masses. Results are re-ported as (1) negative (benign), (2) positive (malignant), (3) in-determinate (suspicious), and (4) inadequate (nondiagnostic).
In a thyroid scan, a scintillation detector or gamma camera moves back and forth across the area to be studied in a series of parallel tracks, and a visual image is made of the distribution of radio-activity in the area being scanned. Although 123I has been the most commonly used isotope, several other radioactive isotopes, including technetium-99m (99mTc) pertechnetate, thallium, and americium, are also used.
Scans are helpful in determining the location, size, shape, and anatomic function of the thyroid gland, particularly when thyroid tissue is substernal or large. Identifying areas of increased function (“hot” areas) or decreased function (“cold” areas) can assist in di-agnosis. Although most areas of decreased function do not repre-sent malignancies, lack of function increases the likelihood of malignancy, particularly if only one nonfunctioning area is present. Scanning of the entire body, to obtain the total body profile, may be carried out in a search for a functioning thyroid metastasis.
Ultrasound, CT scans, and MRI may be used to clarify or con-firm the results of other diagnostic studies. Thyroglobulin (Tg), a precursor for T3 and T4, can be measured reliably in the serum by radioimmunoassay. Clinically, it is used to detect persistence or recurrence of thyroid carcinoma.
When thyroid tests are scheduled, it is necessary to determine whether the patient has taken medications or agents that contain iodine because these may alter the test results. Iodine-containing medications include contrast agents and those used to treat thyroid disorders. Less obvious sources of iodine are topical antiseptics, multivitamin preparations, and food supplements frequently found in health food stores; cough syrups; and amiodarone, an antiar-rhythmic agent. Other medications that may affect test results are estrogens, salicylates, amphetamines, chemotherapeutic agents, antibiotics, corticosteroids, and mercurial diuretics. The nurse asks the patient about the use of these medications and notes their use on the laboratory requisition. Chart 42-1 gives a partial list of agents that may interfere with accurate testing of thyroid gland function.
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