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Continuing Education Continuing Education Thyroid Imaging Studies Helen H. Drew, Norman D. LaFrance, and James J.S. Chen 77Je Johns Hopkins Medical Institutions, Baltimore, Maryland This is the second in a series of Continuing Education articles thyro. meaning shield. which is quite descriptive of the related to functional/quantitative imaging techniques. After reading thyroid's shape. The isthmus overlies the trachea anteriorly this article, the reader should be able to: 1) discuss the clinical and is located just caudal to the level of the cricoid cartilage applications ofthyroid imaging; 2) understand the relationship of with each thyroid lobe extending laterally. A narrow strip of related thyroid tests; and 3) recognize the pitfalls and problems thyroid tissue called the pyramidal lobe may also be seen. The associated with this procedure. pyramidal lobe extends upward from the isthmus along the thyroid cartilage. During embryonic development the thyroid Thyroid imaging has had a long run as an important nuclear is derived from endodermal tissue in the region of the first medicine evaluation. Although evolved and expanded in scope. pharyngeal pouch. The median outgrowth migrates downward the unique functional and structural information obtained along and bifurcates at the lower end to form the lateral lobes and with excellent cost effectiveness and safety has not been isthmus. Because of this embryonic migration normal thyroid duplicated optimally by other nontracer modalities. Our tissue may be found from the base of the tongue to the level emphasis is directed at thyroid imaging: however. a complete of the diaphragm. thyroid study requires correlation with thyroid function The thyroid's arterial blood supply arises from both the studies. clinical history. and physical examination. A brief external carotids. which give off the superior thyroid arteries basic review of the thyroid may help enhance this overview and the subclavian arteries. which supply the inferior thyroid article. arteries accounting for a highly vascularized gland. The thyroid gland enjoys an important place in the history The structural and functional unit of the thyroid gland is of nuclear medicine. It was among the first organs to be studied the thyroid follicle. Spherical in shape with an average by radioactive tracers and the first to be imaged by scintillation diameter of 300 pm. the wall is composed of cuboidal epithelial technique after the administration of radioiodine. This was cells arranged in a single layer. The thyroid follicular cells reported in 1951 in two separate articles by Allen et a!. (1) are the site of thyroid hormone synthesis. and the follicle lumen and Cassen et al. (2). whose techniques by today's standards functions as a storage unit. were relatively basic. Since these first reports. significant im­ provement has occurred in instrumentation while changes in Physiology and Pathophysiology the radiopharmaceuticals have lowered the patient's dose The primary function of the thyroid gland is to synthesize. equivalent and have allowed for the evaluation of an even store, and secrete the thyroid hormones thyroxine (T.) and broader spectrum of thyroid disorders. triiodothyronine (T). Thyroid hormones exert a peripheral metabolic effect. including influence on growth and THE THYROID GLAND development. regulation of every organ system, and Anatomy temperature homeostasis. along with carbohydrate. lipid, protein, nucleic acid. vitamin. and mineral metabolism. The The thyroid gland is located in the anterior neck with its principal mechanism of action appears to be mediated by a two lobes extending from the thyroid cartilage to just above receptor localized in the cell's nucleus. which modulates DNA the suprasternal notch bilaterally. The gland consists of two and RNA synthesis. which in turn influences protein synthesis. lateral lobes joined by a thin band of tissue. the isthmus. For example, when T levels are increased DNA and RNA inferiorly. The gland's name is derived from the Greek word 4 synthesis is accelerated. and therefore protein synthesis is increased (3). The regulation of thyroid hormone synthesis and secretion For is controlled by a negative feedback Elechanism of thyroid n:prinh contact: Hekn Drew. ~uclear Medicine. The John' Hopkin' hormone on the anterior pituitary and the hypothalamus. Hmpital. 600 :'\.Wolfe Street. Baltimore. MD ~1~05. 15, NUMBER 2, JUNE 1987 79 VOLUME Thyrotropin releasing factor (TRF) is secreted by the hypothalamus into the portal vessels of the pituitary stalk and is transported directly to the anterior pituitary. Thyroid stimulating hormone (TSH) synthesis by the anterior pituitary is stimulated by TRF. resulting in increased blood levels of TSH. At the level of the thyroid. TSH regulates thyroidal uptake of iodide (I ) synthesis and release of hormone into the circulation. with increased TSH upregulating all of these Pituitary thyroid actions. Trapping. The first step in the synthesis of the thyroid hormone is the extraction of iodide from the blood by the thyroid gland. Dietary ingested iodine in the United States has Negative greatly increased in recent years due to iodine supple­ feedback mentation. Ingested iodine is reduced to iodide in the upper Free 0.03% T4 Iodide intestine. In the first 60 min after ingestion. approximately 0.3% Free T3 90% is absorbed and distributed into the vascular space. This energy-dependent iodide concentrating mechanism of the thy­ roid gland. referred to as the iodide trap. is linked to the Na-. K--ATPase-dependent transport system and is carried T4' T3 out by the thyroid follicular cells. Thyroidal iodide Bound to binding proteins 99.97% T4 Bound concentrations normally reach levels of 25-30 times that of 99. 7 % T Bound the plasma level (4). 3 Organification. The next step in thyroid hormone synthesis FIG. 1. Hypothalamic-pituitary-thyroid axis. takes place at the surface of the thyroid follicular cells (de­ scribed as the colloid aspect of the follicular cell) and is free T and T levels may differ from the total T and T4 values. referred to as organification. The trapped iodide is oxidized 3 4 3 Currently it is believed that both free T and free T exert to iodine catalyzed by a peroxidase and H 0 mechanism. The 4 3 2 2 biologic activity ( 6). but T is the more physiologically active oxidized iodide then reacts with the tyrosyl moiety of thyro­ 3 of the two thyroid hormones in spite of its 60 times lower globulin to form monoiodotyrosine globulin and diiodotyrosine concentration compared to T • The majority of circulating TJ globulin. Thyroglobulin is a glycoprotein that contains 120 4 results from the 5 1 monodeiodination of T in the peripheral tyrosine residues and is stored in the folliclar lumen. 4 tissues and is not solely derived from thyroid gland synthesis. Coupling. Coupling of two diiodotyrosine molecules forms A 5-position monodeiodination (rather than 5 I as noted above) T4, whereas the combination of one monoiodotyrosyl molecule of T4 can occur in certain clinical conditions. such as chronic and one diiodotyrosyl molecule forms T3 . Both T4 and TJ are illness. prolonged stress, and starvation, forming reverse T • the physiologically active thyroid hormones. Thyroid hormone 3 Reverse T is much less metabolically active than T • is then stored in the follicle bound to thyroglobulin until 3 3 An elegant negative feedback mechanism exists to control needed. thyroid activity. The free thyroid hormone exerts a direct effect Release. Proteolytic enzymes release T4 and T3 from thyro­ upon the pituitary by inhibiting synthesis and secretion ofTSH, globulin and the free thyroxine and triiodothyronine enter the thereby decreasing the stimulation of the thyroid gland to make peripheral circulation (5). This release is stimulated by TSH. thyroid hormone. The free thyroid hormone may also directly Once in the peripheral circulation. T and T bind almost 4 3 affect the hypothalamus. Figure I illustrates the normal regula­ completely to a specific plasma protein. thyroxine-binding­ tory mechanism for thyroid hormone production. This mech­ globulin (TBG). T4 also binds to a T4 binding prealbumin anism is referred to as the hypothalamic-pituitary-thyroid axis. (TBPA) and to albumin. These plasma proteins provide the Recent studies indicate it is likely the T3 within the pituitary, transport vehicle to the peripheral tissues, and prohibit the rather than the T4, that regulates TSH secretion. Intracellular thyroid hormones from exhibiting their metabolic effects. T3 T3 in pituitary thyrotrophs comes from two sources. One is principally bound by TBG. but there is much less affinity source is the intravascular free T3 that enters directly from ofTBG for T3.1t is the nonbound thyroid hormone that exhibits the bloodstream; a more important source is the T converted its physiologic effects. Specifically. 99.97% of plasma T4 and 3 intracellularly from T4 that occurs within the pituitary itself. 99.7% of plasma T3 are protein bound, and only the 0.03% As a result, the thyrotrophs, which possess an active T4 free T4 and 0.3% free T3 are available to exert their physiologic 5!deiodinase, are relatively more dependent on circulating T4 effects. This concept becomes important in a variety of condi­ than T3 for feedback inhibition. tions because although free and total hormone values typically correlate. a number of disorders (e.g .. nonthyroidal illness. Pathophysiology drugs, etc.) can affect TBG or TBG binding sites and change Defects in thyroid hormone production can involve any of total hormone levels. In this case total hormone values should the steps mentioned above. This results in either an under- or be interpreted with caution since the physiologically pertinent an overproduction of thyroid hormone. This in turn influences 80 JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY metabolic effects upon various organ systems and emphasizes of the thyroid. Other inflammatory processes may cause thy­ the importance of thyroid function tests. which may need to roiditis and can be secondary to bacterial, fungal, or viral be complemented by imaging techniques.
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