13 Thyroid, Parathyroid, and Adrenal Gland Imaging William H. Martin, Martin P. Sandler, and Milton D. Gross 13.1 The Thyroid 13.1.2 Physiology 13.1.1 Anatomy An appreciation of thyroid physiology and patho- physiology is essential for the optimal manage- The thyroid is a bilobed structure evolving from ment of thyroid disorders. The function of the the fourth and fifth branchial pouches. It is ini- thyroid gland includes the concentration of io- tially attached to the ventral floor of the pharynx dine, synthesis of thyroid hormones, storage of by the thyroglossal duct. Thyroid tissue may be these hormones as part of the thyroglobulin (Tg) found anywhere between the base of the tongue molecule in the colloid, and their secretion into and the retrosternal anterior mediastinum (Fig- the circulation as required. Over 99% of circu- ure 13.1). The fetal thyroid gland begins to con- lating thyroid hormones are bound to plasma centrate iodine and synthesize thyroid hormones proteins, primarily thyroxine-binding globulin by approximately 10.5 weeks, which is pertinent (TBG). Only the unbound fraction of thyroid hor- when the administration of 131I to fertile women mone is metabolically active and, for this reason, is contemplated. The two ellipsoid lobes of the accurate assays of free thyroid hormone, “free T4” adult thyroid are joined by a thin isthmus. Each and “free T3”, have been developed. lobe is approximately 2 cm in thickness and Dietary sources of iodine include seafood, milk, width and averages 4–4.5 cm in length. The thy- eggs, and iodized products such as salt and bread. roid gland, averaging approximately 20 grams in Approximately one-third of the absorbed dietary weight, resides in the neck at the level of the cricoid iodide is trapped by the thyroid, the remainder cartilage. A pyramidal lobe is present in approxi- being excreted in the urine. Although gastric mu- mately 30–50%, arising from either the isthmus or cosa, salivary glands, and the lactating breast may the superomedial aspect of either lobe; it under- also trap iodide, none of these organify it. The con- goes progressive atrophy in adulthood but may centration of iodide by the thyroid gland, synthe- be prominent in patients with Graves’ disease. sis, and release of thyroid hormones are under the Although the right lobe tends to be somewhat regulatory control of the hypothalamic-pituitary- larger than the left lobe, there is a great deal of thyroid axis. Thyroid stimulating hormone (TSH) variability in both size and shape of the normal from the pituitary plays the major role in reg- gland. ulating thyroid function and this, in turn, is 247 248 PRACTICAL NUCLEAR MEDICINE Figure 13.1. Normal and aberrant locations of thyroid tissue. under the control of hypothalamic thyrotropin- play an important role in the investigation of releasing hormone (TRH) secretion. The present patients with thyroid disorders, especially those third generation assay for circulating TSH is highly with thyroid nodules. RAIU is discussed in Sec- sensitive and represents the most sensitive bio- tion 4.12. chemical indicator of both hypothyroidism and hyperthyroidism; the serum TSH is elevated to above 5 mIU/l with even subclinical primary hy- Thyroid Scintigraphy pothyroidism and is suppressed usually to un- With the development of fine needle aspiration detectable levels with hyperthyroidism. Numer- biopsy (FNA) for evaluation of nodular disease ous exogenous factors such as systemic illness, combined with the exquisite anatomic detail pro- nutritional status, thionamides, beta blockers, vided by sonography, CT, and MRI, the use of steroids, iodide, lithium, amiodarone, and anti- thyroid scintigraphy has decreased appropriately. convulsants, may affect thyroid hormone secre- However, it will continue to play an important role tion and metabolism. in the functional evaluation of a variety of thyroid disorders as well as the detection of metastatic thy- 13.1.3 Clinical Applications roid cancer. Technetium-99m pertechnetate is the most readily available radionuclide employed for − Radionuclide imaging and the measurement of thyroid imaging. Pertechnetate ions (TcO4 )are thyroid radioactive iodine uptake (RAIU) both trapped by the thyroid in the same manner as 249 THYROID, PARATHYROID, AND ADRENAL GLAND IMAGING Table 13.1. Thyroid scintigraphy Radiopharmaceutical [99mTc]pertechnetate [123I]sodium iodide Activity administered 80–370 MBq (2–10 mCi) 20 MBq (500 µCi) Intravenous Oral or intravenous Effective dose equivalent 1–5 mSv (200–400 mrem) 4 mSv (400 mrem) Patient preparation Withdrawal of thyroid medication, avoidance Withdrawal of thyroid medication, avoidance of of foodstuffs with high iodine content foodstuffs with high iodine content Collimator Pinhole; low-energy, high-resolution Pinhole; low-energy, high-resolution parallel-hole; low energy converging parallel-hole; low energy converging Images acquired Imaging started 15 min post-injection Imaging started 1–2 h post-injection if intravenous or 24 h if oral Anterior, right and left anterior oblique Anterior, right and left anterior oblique views views, 600 second exposure per image or 200 kcounts/image iodine through an active iodine transporter, but equivalent [1]. 123I imaging is used in specific pertechnetate ions are not organified. 123Iodine is situations,suchasretrosternalgoiter.Theprotocol both trapped and organified by the thyroid gland, for thyroid imaging is given in Table 13.1. allowing overall assessment of thyroid function. The normal thyroid scintigram is shown in Since 123I is cyclotron-produced and has a rel- Figure 13.2. High-resolution images are obtained atively short half-life of 13.6 hours, it is more by using a pinhole collimator, thus permitting the expensive and advance notice is necessary for detection of nodules as small as 5 mm in diameter. imaging. Because of its inferior image quality and The oblique views permit detection of small nod- the high thyroid and total body radiation dose ules obscured by overlying or underlying physio- from its β-emission, 131I is not used for routine logical activity. Pinhole SPECT has been used to thyroid imaging other than for metastatic thyroid better detect subtle abnormalities. The radionu- cancer assessment. Due primarily to less back- clide is distributed homogeneously throughout ground activity, 123I imaging provides somewhat the gland with some increase seen centrally due higher quality images than 99mTc, but the diag- to physiological thickness of the gland there; ac- nostic information provided by each is roughly tivity within the isthmus is variable and must Figure 13.2. Normal 99mTc thyroid scan. Symmetric, homogeneous uptake with less intense salivary gland uptake and only mild back- ground uptake. The inferior activity is due to a 57Co marker at the suprasternal notch. 250 PRACTICAL NUCLEAR MEDICINE Figure13.3. Subtlecoldnodule. 99mTcpertechnetateanteriorviewademonstratesasubtlehypofunctioningleftlowerpolenoduleextending into the isthmus, confirmed on a subsequent contrast-enhanced CT b to be a thyroid cyst. In the euthyroid gland, thyroid activity should be greater than that of the salivary glands. Anatomic variations are relatively frequent and may include agenesis, hemiagenesis, and ectopia (Figure 13.4) as well as mere asymmetry. Ectopia is typically associated with hypothyroidism. Sig- nificant concavity of the lateral margin should be considered suspicious of a hypofunctioning nod- ule, and exaggerated convexity is often seen with diffuse goiters. The pyramidal lobe, a remnant of the distal thyroglossal duct, is identified in less than 10% of euthyroid patients, but is visualized in as many as 43% of patients with Graves’ disease (Figure 13.5). Extrathyroidal accumulation of the radiopharmaceutical usually represents ectopic thyroid tissue or metastatic thyroid carcinoma if gastroesophageal and salivary gland activity can be excluded. Multinodular Goiter Figure 13.4. Lingual ectopic thyroid. An anterior 99mTc pertechne- tate image demonstrates a focus of activity at the base of the tongue The patient with multinodular goiter (MNG) may in this neonate. Cervical thyroid uptake is absent. present with what seems to be a solitary thyroid nodule, diffuse enlargement of the gland, or hy- perthyroidism. Development of MNG is related be correlated with physical examination and/or to cycling periods of stimulation followed by in- other imaging (Figure 13.3). With pertechnetate, volution and may be idiopathic or occur as a re- salivary glands, gastric mucosa, esophagus, and sult of endemic iodine deficiency. Over time the blood pool background are seen in addition to gland enlarges and evolves into an admixture of thyroid activity. Due to delayed imaging, salivary fibrosis, functional nodules, and non-functioning gland activity is often absent with 123I imaging. involuted nodules. Scintigraphically, the MNG 251 THYROID, PARATHYROID, AND ADRENAL GLAND IMAGING biopsied. The differential diagnosis includes au- toimmune Hashimoto’s thyroiditis, multiple ade- nomas, and multifocal carcinoma. Further char- acterization of the gland with ultrasound, CT, or MRI does not appreciably aid clinical diagnosis. Thyroid Nodules The management of patients with a solitary thy- roid nodule remains controversial, related to the high incidence of nodules, the infrequency of thy- roid malignancy, and the relatively low morbid- ity and mortality associated with differentiated thyroid cancer (DTC) [2]. Thyroid nodules may contain normal thyroid tissue, benign hypofunc- tioning tissue (solid,