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Thyroid function test: a clinical lab perspective.


To earn CEUs, see test on page 18.


Upon completion of this article, the reader will be able to:

1. List hormones and functions of hormones produced by the thyroid and other glands required for thyroid function.

2. Evaluate data to determine which thyroid disease is most likely.

3. Recognize mechanisms of thyroid hormone production including iodine uptake.

4. Recognize the location, cell types, and size of the thyroid gland.

5. Recognize assays used to diagnose thyroid disease and the sensitivity for TSH assays.

6. Recognize mechanisms, symptoms, signs, and treatment of thyroid disease.


Thyroid hormones participate in regulating metabolic processes, neurologic development, and other body processes through the production of thyroid hormones and calcitonin. Calcitonin, which is involved in calcium homeostasis, is produced by the parafollicular C cells. The thyroid gland is shaped like a butterfly, divided into two lobes connected by the isthmus, and is located in the lower anterior neck. The two lobes are situated on either sides of the trachea. Measurements of thyrotropin (TSH) and free thyroxine ([FT.sub.4]) are the most useful tests for assessing thyroid function. Other tests that may be used to evaluate patients with thyroid disorders include antithyroglobulin antibodies, antithyroid peroxidase antibodies, free T4 index ([FT.sub.4]I), total triiodothyronine and so forth. Hypothyroidism causes low metabolism, while hyperthyroidism precipitates increased metabolism. Thyrotropin releasing hormone (TRH) stimulates the anterior pituitary gland to synthesize and release TSH, which, in turn, stimulates the thyroid gland to release thyroid hormone. A familiarity by healthcare providers of the symptoms, diagnosis, and treatment of thyroid disorders is essential for success in caring for patients with thyroid disease.



The thyroid gland is located in the lower front of the neck, weighs approximately 15 grams to 20 grams in an adult and is made up of two types of cells, follicular and parafollicular. Thyroid hormones are produced by the follicular cells and are then stored in the colloid located in the central part of the spherical follicle. The parafollicular cells secret calcitonin and, hence, are called C cells. The thyroid follicle is the secretory unit of the thyroid gland and consists of an outer layer of epithelial cells that encloses the colloid. The colloid is composed essentially of thyroglobulin (Tg) and small amounts of iodinated thyroalbumin. (1) The main function of the thyroid gland is the synthesis of thyroid hormone, which is secreted into the blood and transported to every tissue of the body. The hormone assists the body in its use of energy and to stay warm, and helps all the organs to work properly. Thyroxine ([T.sub.4]) is the major hormone secreted by the thyroid gland. Two other hormones secreted in minute quantities are monoiiodotyrosine (MIT) and diiodotyrosine (DIT), which are precursors of triiodothyronine ([T.sub.3]) and [T.sub.4].

In order for [T.sub.4] to perform its function, it is first converted to [T.sub.3] through the removal of an iodine atom. This process takes place mainly in the liver and the brain where [T.sub.3] acts. [T.sub.3] is four to five times more potent than [T.sub.4]. The main function of the thyroid hormones is the control of energy expenditure and, in addition, their functions include growth, development, and sexual maturation. (1) Thyroid hormones also participate in the stimulation of heart rate and contraction, stimulation of protein synthesis, carbohydrate metabolism, synthesis and degradation of cholesterol and triglycerides, and the enhancement in sensitivity of [beta]-adrenergic receptors to catecholamine. The quantity of [T.sub.4] produced by the thyroid gland is controlled by TSH, which is produced by the pituitary gland. The amount of TSH produced by the pituitary gland is dependent on the amount of [T.sub.4] present in the blood. When the level of [T.sub.4] is low, the pituitary gland produces more TSH--and when the level of [T.sub.4] is above a certain level, the pituitary shuts off the production of TSH through a negative feedback mechanism. The secretion of TSH is in turn regulated by TRH, which is produced by the hypothalamus. (2)

Biochemistry and physiological considerations

Many foods contain iodine, and extra amounts of iodine may be provided by the ingestion of iodine-enriched foods. Iodine intake in the United States ranges from 250 [micro]g to 700 [micro]g or more daily. (3) In countries like Japan, intake may reach several milligrams per day, whereas in areas such as Africa, South America, Asia, and Europe daily intake may be as low as 50 [micro]g. Iodine is absorbed in the small intestine and then enters either the excretory or metabolic pathways. Subsequently, between 60% and 80% of the ingested iodine is excreted by the kidneys; small amounts are excreted through the intestine. Some of the iodine is degraded by the liver and excreted into the bowel by the biliary tract. The remainder is distributed into the extracellular and thyroid compartment. About 90% of the total body iodine, which amounts to as much as 6,000 [micro]g to 12,000 [micro]g is contained in the intrathyroid iodine compartment.

The production of thyroid hormones involves the trapping of serum iodide by the thyroid gland. This is followed by the incorporation of iodine into tyrosine, coupling of iodinated tyrosyl residues of Tg, and the release of iodothyronines through the proteolytic cleavage of follicular Tg. (1) The synthesis of thyroid hormones requires iodine, which is ingested in the form of iodide. The transport of iodide to the follicle is the first rate-limiting step in the synthesis of thyroid hormones. The site of the synthesis of [T.sub.3], [T.sub.4], DIT, and MIT in Tg molecules is follicular cell-colloid interface as well as within the colloid. Peptide bonds between iodinated residues and Tg are broken by lysosmal enzymes, followed by the diffusion into the systemic circulation of the [T.sub.4] and [T.sub.3] that is produced. The deiodination of DIT and MIT takes place in the follicular cells, and the freed iodide is recycled. In addition to regulating the thyroid gland, the increase in the size and number of the follicular cells of the thyroid gland is induced by TSH. A consequence of prolonged stimulation of the thyroid gland is increased vascularity and hypertrophic enlargement of the thyroid gland--otherwise known as goiter. Conjugation of [T.sub.3] and [T.sub.4] in the liver leads to the formation of sulfates and glucuronides, which enter the bile and pass into the intestine.

A relationship exists among the thyroid gland, hypothalamus, and the pituitary gland. The hypothalamus produces TRH, which acts on the pituitary thyrotropes to stimulate the synthesis and release of TSH. There is a circadian variation in the concentration of circulating TSH depending on the time of day. The concentration is low during the day, increases in the evening, and peaks before sleep. (4)


There is a continuing debate on the prevalence of abnormal thyroid function due to the differences in prevalence estimates in various countries for hypothyroidism and hyperthyroidism. Disease definition, diverse populations for the studies, and the fact that the measurement of thyroid function tests is insensitive is the reason for the continued debate. (5) A study involving women and men of all ages in Wickham, England, found the serum TSH levels greater than six mIU/L in 7.5% of women and 2.8% of men. (6) The incidence of thyroid dysfunction in the Wickham Study in the United Kingdom is reported as 100 to 200 cases per 100,000 population per year. According to the Third National Health and Nutrition Examination Survey (NHANES III), 4.6% (0.3% overt and 4.3% subclinical) and 1.3% (0.5% overt and 0.7% subclinical) of the total population were found to have hypothyroidism and hyperthyroidism, respectively. (7) About 4.1 million men and 8 million women have subclinical hypothyroidism in the United States. In women older than 60 years in the United States, 13.6% were found to have TSH greater than five mIU/L. Serum TSH levels greater than five mIU/L were found in only 1.5% of Italian women of similar age as their U.S. counterparts--in spite of the fact that dietary iodine is low in Italy. (5)

Thyroid dysfunction which is unrecognized at the time of patient hospitalization for acute illness is believed to be as common. (8) In the United States, subclinical forms of hyperthyroidism and hypothyroidism found especially in the older population contribute to the development of osteoporosis, hyperlipidemia, hyperhomocysteinemia, as well as cardiovascular and neuropsychiatric disease. (9) Significant changes are observed during pregnancy such as a two- to three-fold increase in the concentration of thyroxine-binding globulin (TBG), a 30% to 100% increase in total [T.sub.3] ([TT.sub.3]) and [T.sub.4] concentration, increased serum Tg, and increased renal iodide clearance. (10)

Iodine metabolism and synthesis of thyroid hormones

The metabolism of iodine takes place in the thyroid gland. The process consists of the following five steps: iodine uptake by the cells of the follicle, organification, coupling, storage, and secretion. Concentration of iodine depends on active energy at the level of cell membrane and occurs during uptake by the thyroid cells against high chemical and electrical gradients. The process requires stimulation by TSH, and the presence of excess iodine inhibits iodine transport while it is stimulated by iodine deficiency. The process whereby iodine is incorporated into the thyroid hormone is known as organification. In the thyroid, iodine is oxidized into a reactive form that combines with the protein Tg in the presence of a peroxidase enzyme. (3)

Thyroglobulin contains 140 tyrosine residues and serves as the matrix to which reactive iodine is attached to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). After formation, coupling of MIT and DIT through enzymatic reaction takes place leading to the production of intrathyroglobulin [T.sub.3] and [T.sub.4]. Thyroglobulin is released and stored in the colloid of the follicle and iodinated Tg serves as a storage pool of thyroid hormone. The MIT and DIT are deiodinated and their iodine is reused in subsequent thyroid hormone synthesis. The [T.sub.3] and [T.sub.4] are resistant to intrathyroid deiodination and are immediately secreted. (3)

About 80 [micro]g to 100 [micro]g of [T.sub.4] and 7 [micro]g of [T.sub.3] are secreted daily, and the thyroid also secrets small amounts of reverse [T.sub.3] (r[T.sub.3]). The normal secretory product of the thyroid gland is [FT.sub.4], which undergoes peripheral deiodination in the liver to yield [T.sub.3]. Reverse [T.sub.3], which is produced by the removal of one iodine from the inner ring of [T.sub.4], is metabolically inactive and is an end product of [T.sub.4] metabolism. Peripheral deiodination is a rapid responsive mechanism of control for thyroid hormone balance. Acute and chronic stress or illness causes a shift in the direction of this deiodination, which favors the formation of r[T.sub.3] rather than [T.sub.3]. Ninety-nine and 97/100% of [T.sub.4] are bound by carrier proteins such as TBG, thyroxine-binding pre-albumin (TBPA), and albumin. Ninety-nine and 7/100% of [T.sub.3] are likewise bound by the carrier proteins. (3)


Production of increased quantities of [T.sub.4] and [T.sub.3] through a hyperfunctioning thyroid gland may cause hypermetabolic disorder, which can lead to hyperthyroidism. Other causes of thyrotoxicosis include excessive production of thyroid hormones from sources outside the thyroid gland and leakage of stored thyroid hormones from storage in the thyroid follicles. Symptoms of thyrotoxicosis include anxiety, weakness, palpitation, heat intolerance, emotional lability, tremor, increased perspiration, and/or weight loss even with normal or increased appetite (see Table 1). (11) The presence of elevated levels of [T.sub.4] and [T.sub.3] may result in a suppression of TSH production to a level that is undetectable (see Table 2). In cases in which the manifestation of hyperthyroidism is due to a TSH-secreting pituitary tumor, the TSH level would be increased. A diagnosis is usually made on the basis of a low TSH level and elevated levels of [FT.sub.4].

The severity of the disease depends on the increase in the amount of thyroid hormone production. (11) In cases in which the TSH level is low in the presence of normal [FT.sub.4], a measurement of the [T.sub.3] concentration may be a useful diagnostic tool. The [T.sub.3] level is usually increased in early stages of Graves disease, thus measurement of [T.sub.3] and [FT.sub.3] are useful indicators of the severity of thyrotoxicity in hyperthyroidism. TSH, however, is a better indicator of hyperthyroidism since its concentration is typically decreased below normal prior to increases of [T.sub.3] above normal. (12) A common cause of thyrotoxicosis is Graves disease, an autoimmune disorder in which antibodies capable of activating the TSH receptors are produced. The disease presents with goiter, ophthalmopathy, dermopathy, and other symptoms. The condition is more prevalent in females than in males, and there appears to be a familial component.


When the quantity of thyroid hormones reaching the peripheral tissues is inadequate for normal metabolic processes then hypothyroidism is manifested. This may lead to a wide variety of clinical diseases. Symptoms of hypothyroidism include cold intolerance, fatigue, dry skin, weight gain, cognitive dysfunction, mental retardation in infants, dyspnea on exertion, edema, depression, and pubertal delay (see Table 1). (11) The patient with hypothyroidism may initially be asymptomatic and, thus, may not consult a physician. (13) Hypothyroidism is commonly seen in women, especially in those with advancing age. A common and primary cause of hypothyroidism is a disease in the thyroid gland while a secondary or tertiary cause is usually due to disorders in the pituitary or hypothalamus respectively. Biosynthetic defects may lead to an enlarged thyroid gland commonly known as goiter. Destruction of the thyroid gland or the resistance of peripheral tissues to thyroid hormone may also lead to hypothyroidism.

In developed countries, Hashimoto's thyroiditis is usually the cause of primary hypothyroidism while worldwide the most common cause is iodine deficiency. A common diagnostic feature of hypothyroidism is increased levels of TSH with small decreases in [T.sub.4] and [T.sub.3] levels (see Table 2). A survey of 2,779 inhabitants of Wickham, England, showed that 7.5% and 2.8% of the women and men, respectively, had an increased serum TSH. (6) Sawin, et al, using the Framingham database showed that 11.7% and 3.9% of women and men, respectively, and 8.5% persons over the age of 60 years had hypothyroidism. (13) In subclinical hypothyroidism, the TSH level is usually elevated (TSH level of >4.0 mIU/L) in the presence of normal levels of thyroid hormones ([FT.sub.4] of 11 pmol/L to 25 pmol/L [0.9 to 1.9 ng/dL]). (14) Thus, the biological marker for hypothyroidism is TSH. Consequently, it is often necessary to monitor the serum TSH level in order to achieve clinical euthyroidism during therapy. Absence of the thyroid gland or defects in hormone synthesis may result in congenital hypothyroidism. This requires early detection and treatment in order to prevent mental retardation. Most of the developed world has instituted early-screening programs, which utilize measurements of [T.sub.4] and TSH on infants that present with low [T.sub.4] values. A disease of the pituitary or the hypothalamus leading to a decreased production of TSH may precipitate the hypothyroidism. In the presence of low [T.sub.4] and TSH, a measurement of TRH hormone may help in distinguishing a pituitary problem from a dysfunction of the hypothalamus. (1)

Euthyroid sick syndrome

A distinguishing characteristic of euthyroid sick syndrome, which is seen in clinically euthyroid patients suffering from nonthyroidal systemic illness is the presence of abnormal thyroid function tests. These patients most often present with abnormal thyroid function tests such as decreased conversion of [T.sub.4] to [T.sub.3], as well as decreased clearance of r[T.sub.3] and a reduction in the binding of thyroid hormone to TBG. (15) This syndrome has been associated with various conditions such as fasting, protein-caloric malnutrition, starvation, myocardial infarction, diabetic ketoacidosis, and cirrhosis. Laboratory tests usually show decreased [TT.sub.3], increased r[T.sub.3], normal or decreased [TT.sub.4], and variable TSH.

Laboratory investigation of thyroid function

Measurement of thyroid hormones may be obtained from peripheral blood samples; and for routine clinical use, measurement of TSH and [FT.sub.4] is effective in the diagnosis of thyroid dysfunction. Other thyroid funtion tests include resin uptake, [T.sub.3], [FT.sub.3], r[T.sub.3], TBG. (3,4) Various testing methods are available for the determination of TSH such as radioimmunoassay (RIA), immunoradiometric assay (IRMA), immunochemilumino-metric assay (ICMA), and time-resolved immunofluorometric assay (TR-IFMA). Second-generation IRMA and ICMA have functional sensitivity of 0.1 mIU/L to 0.2 mIU/L, third-generation assays have a functional sensitivity of 0.01 mIU/L to 0.02 mIU/L, and fourth-generation assays have a functional sensitivity of 0.001 mIU/L to 0.002 mIU/L. Thyroxine analysis may be performed by employing RIA, enzyme-multiplied immunoassay (EMIT), fluorescence polarization immunoassay (FPIA). cloned enzyme-donor immunoassay (CEDIA), ICMA, and fluorometric enzyme immunoassay (FEIA). Immunometric assays can measure [TT.sub.4], both bound and free hormone. In the past, protein-bound iodine was the test used for the indirect assessment of the concentration of thyroid hormone in the blood. This test is now of only historical interest and has been replaced by more accurate diagnostic tests. (3)

Thyroid hormones in blood are either bound or free and, thus, the concentration of binding protein can influence the variation in total thyroid hormones in the blood. The appearance of either hypothyroidism or hyperthyroidism will depend on the existence of a net persistent decrease in the level of free thyroid hormones. The American Thyroid Association recommended in 1990 that free thyroid hormone be measured directly or indirectly in the investigation of thyroid disease. A knowledge of the level of TBG in blood is required in order for the measurement of [T.sub.4] and [T.sub.3] to be clinically meaningful. A resin-uptake test can be used to measure the ability of TBG. (3) TBG is increased during pregnancy by estrogen therapy, oral contraceptives, during the acute phase of infectious hepatitis, and decreased by anabolic steroids including testosterone and excess quantities of corticosteroids.


The metabolic and biological effect of thyroid hormone on target cells is induced by the free hormone. An indirect estimate of the concentration of [FT.sub.4] in the blood may be obtained with the use of [FT.sub.4]I. The [FT.sub.4]I is obtained from the [TT.sub.4] and resin-uptake values determined from the serum samples and employing the following formula:

[FT.sub.4]I = Total serum [T.sub.4] X % T uptake of patient serum/% T uptake of pooled reference serum

To obtain the [FT.sub.3]I, the same formula is used except that [TT.sub.3] is used in the calculation. A diagnostic algorithm is shown in Figure 1. Over the past decade, however, [FT.sub.4] and [FT.sub.3] measurements have improved analytical accuracy in preference to [FT.sub.4] I and [FT.sub.3]I.

Thyroid-stimulating hormone test

Over the past 20 years, a great deal of improvement has been achieved in the sensitivity of TSH measurement. TSH is a good measure of thyroid function, and the standard method of measurement is the immunoassay. Immunometric assays (IMA) are highly sensitive and can measure TSH levels as low as between 0.01 mIU/L and 0.02 mIU/L required for routine clinical assessment of thyroid function. TSH assay sensitivity is judged on its ability to differentiate a euthyroid level from very low levels typical of Graves thyrotoxicosis (<0.01 mIU/L). (16) The TSH may be used as a single test screen for thyroid function and the estimation of [FT.sub.4] may be reserved for patients who are found to have abnormal concentrations of TSH. (17) A high TSH level is indicative of a failing thyroid gland leading to primary hypothyroidism. When the TSH is low, that might indicate a hyperactive thyroid leading to overproduction of thyroid hormone. Low TSH values (<0.1 mIU/L) might also be due to an abnormality in the pituitary gland, which may prevent it from making enough TSH to stimulate the thyroid gland, leading to secondary hypothyroidism. A normal TSH is usually indicative of a properly functioning thyroid gland. Although highly sensitive TSH measurements are relevant to the diagnosis of primary thyroid disease, there is evidence that the TSH concentration in serum may be low in some sick patients who are euthyroid. Such decrease may be transient and the level returns to normal as the patient recovers. (18,19) In patients with multinodular goiter or nonthyroidal illness, or those recovering from Graves disease or taking medications, subnormal TSH values may be associated with euthyroidism. (19) Since the therapeutic goal of thyroxine replacement therapy is to maintain serum TSH concentration within its reference range, it is conceivable that measurement of serum TSH is the choice for monitoring replacement therapy.

Thyroxine or [T.sub.4] test

Increased synthesis, release of thyroid hormone from thyroid cells, or binding capacity of plasma proteins such as TBG may contribute to elevation in the level of total serum [T.sub.4]. There are two forms of [T.sub.4] in circulation: [T.sub.4] bound to proteins that prevent [T.sub.4] from entering various tissues, and [FT.sub.4] that can enter the various tissues to exert their effects. The [FT.sub.4] fraction is more important in determining thyroid function. The [FT.sub.4]I is an indirect estimation of the level of [FT.sub.4] in blood. In the presence of hyperthyroidism, the [FT.sub.4] is elevated, whereas in the presence of hypothyroidism, it is decreased. [FT.sub.4]I shows an increased level in hyperthyroidism, and the level is decreased in hypothyroidism. (3) A combination of TSH and [FT.sub.4] can give a good indication of how the thyroid gland is functioning. A low TSH and [FT.sub.4] are indicative of hypothyroidism and might be due to problems involving the pituitary gland. A low TSH with increased [FT.sub.4] is usually seen in patients with hyperthyroidism. [FT.sub.4] may be estimated by measuring both the total [T.sub.4] and the unbound [T.sub.4]-binding sites with radiolabeled [T.sub.3]. A multiplication of [T.sub.3]-uptake result by the total [T.sub.4] results in the [FT.sub.4], which correlates with the [FT.sub.4] concentration. (17)

Triiodothyronine ([T.sub.3]) test

Triiodothyronine is composed of two aromatic rings, which are joined by an ether linkage, three iodine molecules, and an alanine side chain attached to the ring with two iodines. About 80% of circulating form of [T.sub.3] is synthesized through the conversion of [T.sub.4], and the remaining 20% is produced from thyroid gland synthesis and excretion. (12) [T.sub.3] is mostly bound to TBG and, to a lesser degree, to albumin. The metabolically active fraction of [T.sub.3] is the unbound free fraction and its activity is four to five times that of [T.sub.4]. [T.sub.3] tests are helpful in the diagnosis of hyperthyroidism or to determine its severity. In the presence of hyperthyroidism, patients usually run high levels of [T.sub.3], and there is a good correlation between the concentrations of [T.sub.3] and [T.sub.4].

In thyrotoxicosis, the only hormone that is increased is [T.sub.3] and, thus, it can be used to identify patients with the disease who usually have normal [T.sub.4] and [FT.sub.4]. (12) During replacement therapy, measurement of TSH is considered a better monitor than [T.sub.4] or [T.sub.3]. In cases of patients with low albumin concentration, altered thyroxine-binding globulin concentration and abnormal thyroid hormone-binding protein measurement of [FT.sub.3] is better than [T.sub.3]. In some individuals who have low TSH, only [T.sub.3] is elevated and the [FT.sub.4] may be normal. [T.sub.3] is not useful in the diagnosis of hypothyroidism since it is the last test to become abnormal. In patients with Graves hyperthyroidism, ratios of [FT.sub.3] and [FT.sub.4] may be used to predict the outcome of antithyroid drug therapy. Ratios greater than 55 may predict relapse, while ratios less than 55 predict remission. (12) In psychiatric patients treated with orphenadrine, increased levels of [T.sub.3] have been observed while treatment with lithium appears to affect [T.sub.4] but not [T.sub.3]. Depressed patients who are treated with desipramine may present with decreased levels of [FT.sub.4] and TSH, but [T.sub.3] is usually not affected. (12)

Autoantibodies to thyroid peroxidase and to thyroglobulin

A major cause of hypothyroidism in elderly women has been attributed to the prevalence of autoimmune thyroid disease. The antigen for the thyroid microsomal antibody is thyroid peroxidase. Antithyroid antibodies have been found in up to 50% of elderly patients, an occurrence that has been attributed to differences in ethnicity and iodine intake. (21) Measurements of autoantibodies to thyroid peroxidase (TPOAb) and to thyroglobulin (TgAb) are important in the diagnosis and management of autoimmune thyroid disease such as Hashimoto's thyroiditis, primary myxedema, and post-partum thyroiditis. (21) Currently, several different procedures are used to measure these autoantibodies including inhibition of agglutination of antigen-coated particles, enzyme linked immunosorbent assays, coated tubes assays, and immunoprecipitation assays based on [.sup.125]I-labeled TPO or Tg. In the presence of autoimmune thyroid disease, TPOAb was almost certain to be positive in Hashimoto's thyroditis, atropic thyroiditis, post-partum thyroiditis, Graves disease, and very rarely in non-immune thyroid disease. (22)

Thyroglobulin is a high molecular weight glycoprotein of which the thyroid is its only source. In patients with non-toxic or toxic goiter, Tg is usually elevated. Thyroglobulin may be used in the evaluation of patients after near total thyroidectomy with or without [.sup.131]I ablation for differentiated thyroid cancer. The presence of residual normal or malignant tissue in a patient receiving L-thyroxine may be indicated by normal or elevated serum Tg levels. The presence of TgAb may potentially result in underestimation of serum Tg concentration when using current immunometric assay methods. (15)

Radioactive iodine uptake test (RAIU)

The trapping mechanism for iodine may be exploited in clinical tests to assess thyroid function. The test may be used to evaluate thyroid function in the presence of abnormal blood tests for thyroid function. This is a non-blood test in which an individual is given a small amount of radioactive iodine to swallow. By measuring the percentage of an administered dose of radioactive iodine that is taken up by the thyroid gland, it is possible to determine the functionality of the gland. The measurement is obtained at various intervals following the administration of the radioiodine. This can be done four to 24 hours after the dose is given to the patient. (3)

The measurement is performed by placing a gamma probe over the thyroid gland to determine the amount of radioactivity in the thyroid gland. The amount of radioisotope in the thyroid at a given time is a reflection of the synthesis and secretion of thyroid hormone and, thus, reflects the functionality of the thyroid gland. The reference value is 3% to 16% at six hours or 8% to 25% at 24 hours. Elevated values may be obtained in Graves disease, hyperthyroidism, Hashimoto's thyroiditis, and goiter; and low levels may be observed in hypothyroidism, subacute thyroiditis, and iodine overload. Low radioiodine uptake has also been seen in some conditions associated with thyroid hyperfunction such as thyrotoxicosis factitia (that is due to exogenous thyroid hormone) and iodine-induced hyperthyroidism. (3) The test may be performed when the following disorders are present: colloid nodular goiter, Graves disease, silent thyroiditis, and toxic nodular goiter.


Hypothyroidism may be treated with thyroid hormone replacement therapy, and the thyroxine of choice is levo-thyroxine, which is converted to [T.sub.3] in the peripheral circulation. The goal is to achieve normal TSH levels, and the average replacement dose in adults is 1.6 [micro]g/kg body weight. (3,11) Graves disease may be treated with radioactive iodine or surgery to destroy excess functioning thyroid tissue, with thyroid blockers such as propylthiouracil or methimazole to inhibit production and excretion of thyroid hormones and with [beta]-blockers to control symptoms of adrenergic excess such as tremor and tachycardia. (3) Measurement of serum [FT.sub.4] concentration should be performed on a regular basis until the symptoms are resolved and the serum values of [FT.sub.4] return to normal levels.


The thyroid gland produces hormones that are important in the metabolic activities taking place in tissues and organs. The thyroid gland produces [T.sub.4], which is converted into the metabolically active [T.sub.3]. These hormones are essential in the regulation of metabolic processes in the body such as growth and development, and various other functions. A deficiency in thyroid hormone production may be diagnosed through the measurement of TSH. In the case of thyrotoxicosis or hyperthyroidism, there is an overproduction of thyroid hormones, in which case the levels of TSH may be undetectable in the presence of elevated levels of [T.sub.4] and [FT.sub.4]. Awareness of the symptoms, diagnosis, and treatment modalities of thyroid disease by healthcare providers are a necessary requirement for the successful management of patients with thyroid disorders.

Henry Ogedegbe, PhD, BB(ASCP)SC, CLS(NCA), is an associate professor at the University of Medicine and Dentistry of New Jersey in Newark.


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20. Taimela E, Tahtela R, Koskinen P, Nuutila P, Forasstrom J, Taimela S, et al. Ability of Two Thyrotropin (TSH) Assays to Separate Hyperthyroid Patients from Euthyroid Patients with Low TSH. Clin Chem. 1994;40(1):101-105.

21. Roti E, Gardini E, Minelli R, Biaconi L, Braverman LE. Prevalence of Anti-Thyroid Peroxidae Antibodies in Serum in the Elderly: Comparison with other Tests for Anti-Thyroid Antibodies. Clin Chem. 1992;38(1):88-92.

22. Feldt-Rasmussen U. Analytical and clinical performance goals for testing autoantibodies to thyroperoxidase, thyroglobulin and thyrotropin receptor. Clin Chem. 1996;42(1):160-163.


MLO and Northern Illinois University (NIU), DeKalb, IL, are co-sponsors in offering continuing education units (CEUs) for this issue's article on THYROID FUNCTION TEST: A CLINICAL LABORATORY PERSPECTIVE. CEUs or contact hours are granted by the College of Health and Human Sciences at NIU, which has been approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E.[R] program (Provider No. 0001) and by the American Medical Technologists Institute for Education (Provider No. 121019; Registry No. 0061). Approval as a provider of continuing education programs has been granted by the state of Florida (Provider No. JP0000496), and for licensed clinical laboratory scientists and personnel in the state of California (Provider No. 351). Continuing education credits awarded for successful completion of this test are acceptable for the ASCP Board of Registry Continuing Competence Recognition Program. After reading the article on page 10, answer the following test questions and send your completed test form to NIU along with the nominal fee of $20. Readers who pass the test successfully (scoring 70% or higher) will receive a certificate for 1 contact hour of P.A.C.E.[R] credit. Participants should allow four to six weeks for receipt of certificates.

The fee for this continuing education test is $20.

All feature articles published in MLO are peer-reviewed.

Learning Objectives and CE test questions were prepared by Gail S. Williams, PhD, MT(ASCP)SBB, CLS(NCA), Clinical Laboratory Sciences Program, College of Health and Human Sciences, Northern Illinois University, DeKalb, IL.

1. The thyroid gland is located

a. in the chest between the lungs.

b. in the bottom part of the neck in front of the trachea.

c. in the lower part of the neck behind the trachea.

d. in the upper part of neck.

2. Thyroid hormones ([T.sub.3] and [T.sub.4]) are produced by the

a. pituitary gland follicular cells.

b. hypothalamus parafollicular cells.

c. thyroid gland parafollicular cells.

d. thyroid gland follicular cells.

3. Calcitonin is produced and secreted by

a. pituitary gland follicular cells.

b. hypothalamus parafollicular cells.

c. thyroid gland parafollicular cells.

d. thyroid gland follicular cells.

4. The colloid of the thyroid gland is composed primarily of

a. thyroglobulin.

b. iodinated thyroalbumin.

c. thyroxin.

d. triiodothyronine.

5. The major hormone in energy metabolism secreted by the thyroid is

a. monoiodotyrosine.

b. diiodotyrosine.

c. triiodothyronine.

d. thyroxine.

6. [T.sub.4] is converted to [T.sub.3] mainly in the

a. liver and thyroid.

b. brain and thyroid.

c. liver and brain.

d. thyroid.

7. The most potent thyroid hormone involved in energy metabolism is

a. monoiodotyrosine

b. diiodotyrosine.

c. triiodothyronine.

d. thyroxine.

8. TSH is produced by the

a. thyroid.

b. parathyroid.

c. pituitary.

d. hypothalamus.

9. How is thyroid hormone production regulated?

a. When [T.sub.4] levels drop, TSH is produced to increase production.

b. When [T.sub.3] levels drop, TRH is produced to increase production.

c. When [T.sub.4] levels drop, TRH is produced to increase production.

d. When [T.sub.3] levels drop, TSH is produced to increase production.

10. Reverse [T.sub.3] is metabolically active.



11. The best test to follow someone on thyroid hormone replacement therapy is

a. Free [T.sub.4].

b. Free [T.sub.3].

c. TRH.

d. TSH.

12. The best test to follow someone on therapy to reduce thyroid function using radioactive iodine is

a. Free [T.sub.4].

b. Free [T.sub.3].

c. TRH.

d. TSH.

13. Most of ingested iodine is stored in the body.



14. The most sensitive assay(s) for TSH is(are)

a. RIA.

b. fourth-generation IRMA.

c. fourth-generation ICMA.


e. All of the above.

15. Symptoms of thyrotoxicosis include

a. palpitations, heat intolerance, and weight loss with increased appetite.

b. enlarged thyroid, depression, and coarse skin.

c. muscle weakness, fine tremor, and periorbital edema.

d. smooth skin, lid lag, and cold intolerance.

16. The most common cause of hypothyroidism worldwide is iodine deficiency.



17. Euthyroid sick syndrome occurs in patients with

a. defective thyroid glands and normal thyroid function tests.

b. normal thyroid glands, normal thyroid function tests, and systemic disease affecting the function of thyroid hormones in other tissues.

c. normal thyroid glands, systemic disease, and abnormal thyroid function tests.

d. abnormal thyroid glands, abnormal thyroid function tests, and non-systemic illness.

18. A patient with a TSH of 10 mIU/L and [FT.sub.4] of 0.9 ng/dL will most likely be diagnosed as having

a. thyrotoxicosis.

b. Graves disease.

c. euthyroid sick syndrome.

d. hypothyroidism.

19. It is critical to diagnose newborns with hypothyroidism to prevent

a. mental retardation.

b. palpitations.

c. enlarged thyroid.

d. muscle weakness.

20. Autoimmune mechanisms of thyroid disease are seen in both Hashimoto's thyroiditis and Graves disease.




By Henry Ogedegbe, PhD, BB(ASCP)SC, CLS(NCA)
Table 1. Signs and symptoms of hyperthyroidism and hypothyroidism

 Symptoms of thyroid dysfunction
Symptoms Signs

Palpitation Enlarged thyroid
Perspiration Brisk reflexes
Tremor Warm, moist, flushed, smooth skin
Nervousness Tachycardia
Oligomenorrhea Ophthalmopathy
Neck mass Fine tremor
Muscle weakness Lid lag
Exophthalmos Widened palpebral fissures
Weight loss with good appetite Dermopathy
Hyperdefecation Muscle weakness
Fatigue, decreased exercise

 Symptoms of thyroid dysfunction
Symptoms Signs

Growth failure Slow movement and speech
Arthralgia Delayed relaxation of tendon
Depression reflexes
Dyspnea on exertion Bradycardia
Cognitive dysfunction Galactorrhea
Constipation Ascites
Dry skin Periorbital edema
Edema Carotenemia
Menorrhagia Puffy face and loss of eyebrow
Delay of puberty Diastolic hypertension
Weight gain Pleural and pericardial effusions
Cold intolerance Enlargement of the tongue
Hoarseness Coarse skin
Mental retardation in infants
Myalgia and paresthesia

Table 2. Laboratory evaluation of thyroid function

Laboratory evaluation of thyroid function

Pathological condition [T.sub.4] [T.sub.3] [FT.sub.4]

Graves disease High High High
Multinodular goiter High High High
Hyperthyroidism in High High High
Subacute thyroiditis High, normal High, normal High, normal
Trophoblastic tumors High High High
T3 toxicosis Normal High Normal
Neonatal hyperthyroidism High High High
Primary hypothyroidism Low Low, normal Low
Secondary hypothyroidism Low Low Low
Tertiary hypothyrodism Low Low Low
Euthyroid sick syndrome Low, normal Low Low, normal

Laboratory evaluation of thyroid function

Pathological condition [FT.sub.4]I TSH

Graves disease High Low
Multinodular goiter High Low
Hyperthyroidism in High Low
Subacute thyroiditis High, normal Low, normal
Trophoblastic tumors High High, normal, low
T3 toxicosis Normal Low
Neonatal hyperthyroidism High Low, normal
Primary hypothyroidism Low High
Secondary hypothyroidism Low Low, normal
Tertiary hypothyrodism Low Low, normal
Euthyroid sick syndrome Low, normal High, normal, low
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Author:Ogedegbe, Henry
Publication:Medical Laboratory Observer
Article Type:Cover story
Geographic Code:1USA
Date:Feb 1, 2007
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