HEAD AND NECK IMAGING 1052-5149/96$0.00 + .20

PARATHYROID AND IMAGING

David M. Yousem. MD

PARATHYROIDIMAGING imaging, angiography, and scin- tigraphy. The advantages and disadvantages o{ Imaging of the parathyroid glands revolves each of the imaging modalities described are sum- around the detectionof parathvroid adenomasand marized in Table 1. hyperplastic parathyroid glands in the setting oI High frequency (5-10 MHz) ultrasonography is primary . Arguments for and the least invasive of the imaging modalities used against imaging and which imaging modality to to search for parathyroid because it does use have been hotly debated in the radiologic and not require intravenous injections of any com- surgical literature. pounds. Unfortunatelp its accuracy is less than that of the other modalities mainly because of the diffi- culty in identifying ectopic parathyroid adenomas Anatomy and lmaging that may occur throughout the neck, behind air- filled strucfures, or in the anterior The parathyroid glands are derived from the third where acoustic impedance by or air prevents (lower parathyroid glands) and fourth (upper para- adequate imaging. Nonetheless, for parathyroid ad- thyroid glands) pharyngeal pouches.Whereas the enomas that are located in a perithvroidal location. majority of people have four glands (a pair at the ultrasonography is an excellent imaging choice. upper and lower poles of the thyroid gland),25% CT offers the benefit of cross-sectional imaging of individuals have more than this number.3e,a0Al- for parathyroid localization. Because the though the parathyroid glands may be aberrantly entire neck from skull base to anterior mediastinum locatedanywhere from the carotid bifurcation to the can be scanned with CT, the possibility of detecting anterior mediastinum, inferior migration of those ectopic parathyroid adenomas is increased. Distin- glands derived from the third pharyngeal pouch guishing from parathyroid ade- occurs most frequently.3tOf the two dominant cell nomas is a problem encountered with CT (as well as types in the parathyroid glands, the chief cells and with ultrasonography and MR imaging). The other the oxyphil cells, the former are the predominant disadvantage of CT is that it requires the adminis- source of parathormone. tration of iodinated intravenous contrast agents. Vascularsupply to the parathyroid glands is usu- These contrast agents are essential for distinguish- ally through the superior and inferior thyroidal ar- ing blood vessels from adenomas or lymphadenop- teries,with drainage to thyroidal veins. The glands athy. Moreover, the use of iodinated contrast agents are innervated through the cervical sympathetic prevents subsequent imaging with iodine-based nu- plexus. clear medicine agents because of the uptake of con- Thereare severaloptions for imaging the parathy- trast by the thyroid gland. It is necessary to wait at roid glands; these include ultrasonography, com- least 6 weeks after contrast-enhanced CT scans to puted tomography (CT), magnetic resonance(MR) image the thyroid gland with iodinated nuclear

From the Departments of Radiology and -Head and Neck , The University of Pennsylvania Medical Center, Philadelphia, Pennsylvania

NEUROIMAGING CLINICS OF NORTH AMERICA '].996 VOLUME 6 . NUMBER 2. i|'{AY 435 436 YOUSEM

Table1. ADVANTAGESAND DISADVANTAGESOF VARIOUSIMAGING MODALITIES FOR DETECTIONOF PARATHYROIDADENOMAS Examination Advantages Disadvantages CT Examineshead. neck. and chest Requiresiodinated contrast Easy detectionof calcification lodinatedcontrast affects thyroid imaging by Biopsycapable Shoulderartifacts Difficultto differentiatenode versusadenoma Exoensive MR imaging Examineshead. neck. and chest Difficultto differentiatenode versusadenoma No iodinatedconlrast reouired Intravenousgadolinium agent employed Excellentsoft tissuediscrimination Requirespatient cooperation, no claustrophobia Very expensive Nuclearmedicine Examineshead and neck well Loweryield for ectopicglands especially in chest scintigraphy Functional,not anatomicimaging Intrathyroidalmasses indistinguishable from adenomas Distinguishesnodes from adenomas Smallerlesions easily missed Reasonablecost Ultrasonography Examinesneck well Examineshead and chest poorly lnexoensive Cannotdifferentiate nodes and adenomas Noninvasive Real-time,biopsy capable

medicine agents. Contrast enhancement is not the potassium turnover.ae'saBecause sestamibi uptake in solution to parathyroid imaging; only 25% of para- parathyroid adenomas persists after thyroid gland thyroid adenomas demonstrate noticeable enhance- washout, it can be used without subtraction tech- ment.z False-negative studies with CT also may oc- niques if one performs delayed images. The difficult cur in the setting of poor-quality images from task of patient immobilization and accurate su- shoulder artifacts. perimposition of subtracted images, required by MR imaging with gadolinium enhancement is an- thallium-pertechnetate studies, is obviated with de- other useful study for evaluating patients with hy- layed sestamibi imaging. perparathyroidism. On T2-weighted scans and Of the parathyroid agents, thallium emits low- post-gadolinium T1-weighted scans, parathyroid energy, low-penetrating 80 keV photons and adenomas are bright against a dark, fat-suppressed washes out of parathyroid adenomas relatively rap- background.3l'36'56'67'76MR imaging is limited by the idly. ee'Tc-sestamibi has 140 keV photons that pene- distribution and coverage of the surface coil used trate the anterior neck and mediastinal soft tissues to detect parathyroid adenomas and also by any better and is concentrated at a higher rate and for motion artifact that may occur during imaging. a longer time within an adenoma than thallium. Nonetheless, with the appropriate surface coil and ee*Tc-sestamibi, therefore, produces higher signal- instructions to the patient, MR imaging is able to to-noise images than thallium subtraction scans.sa adeouatelv evaluate the entire neck and anterior Single-photon emission computed tomography mediastinum. As with the other modalities listed, (SPECT) scanning also can be combined with high- the potential for misdiagnosing lymphadenopathy dose ee'Tc sestamibi scintigraphy for more accurate as parathyroid adenomas also exists with MR im- localization.ae aging. The choices for scintigraphic localization of para- thgoid adenomas include thallium (Tl)-201-tech- netium (Tc)-99m pertechnetate subtraction scanning, Hyperparathyroidism ee-Tc-sestamibi (hexakis-2-methoxy-isobutyl- isonitrile) subtraction imaging with iodine-123 Hyperparathyroidism has an incidence of 0.0377o ee^Tc-sestamibi present (I-123) or ehTc pertechnetate, and in the United States.28Patients mav with imaging without subtraction. The subtraction the classic findings of stones (renal laiculi), groans technioues allow tracers that are concentrated in (abdominal pain), (demineralization or ar- the thyroid gland (pertechnetate and iodine) to be thritis), or moans (psychiatric disturbances). Pri- subtracted from those (thallium and sestamibi) that mary hyperparathyroidism is caused by a solitary accumulate in both thyroid glands and parathyroid parathvroid adenoma in 80% to 85% of cases.20'21' 6a.s+,ss adenomas. Thallium is a potassium analogue that iltp"rplastic parathyroid glands (12-15%), may concentrate in parathyroid adenomas because multiple adenomas (2-3E"), and parathyroid carci- of changes in potassium turnover in active cells. noma (<2%) account for the remaining 15Vo to 21'58, u,85 The mechanism for sestamibi uptake is poorly un- 20Va.20, Parathyroid adenomas may be ectopic derstood but may relate to mitochondrial density (not around the thyroid bed) in 1,0% to 20Vo of 21,50, 58 in oxyphil cells, blood flow within adenomas, or cases.16, PARATHYROID AND THYROID IMAGING 437

Parathyroid imaging is controversial not only scenario is much lower (<70% successful) than that from the standpoint of the indications for imaging expected for those adenomas in a perithvroidal loca- but also from the issue of which modality (if any) tion(>907o success rate), and the surgiial complica- to choose. In most institutions, preoperative local- tion rate increases with such blind exoorations.l2 ization of the parathyroid glands by imaging is not The intrathvroidal parathvroid adenomi. which ac- performed before the first surgery (for previously counts for a small'percentage of cases, cannot be operated patients, see subsequent discussion). This readily distinguished from thyroid adenomas and stems from the early surgical literature that suggests poses a particularly difficult problem.a5'84To confuse that operative time, morbidity, and mortality is not matters further, thyroidal abnormalities occur in as significantly influenced by preoperative localization many as 40% to 48Vo of patients with hyperpara- of parathyroid adenomas for hyperparathyroid- thyroidism.la 5e.e5 These factors have led less- ism.7' a6,62The surgical exploration entails bilateral experienced surgeons and those who have had a dissection of the perithyroidal region, emphasizing Iess successful track record to choose preoper- the inferior poles, where most parathyroid adeno- ative localization of parathyroid adenomas. mas occur. In experienced hands, this surgical pro- cedure can be performed quickly and accurately Parathyroid Adenomas with success rates of over 90Vo.12'5e,62,65,84This has led Doppman84 to state that the best localization Exactly how accurate are the imaging studies procedure a patient can obtain for parathyroid ade- for detecting parathyroid adenomas? On ultraso- nomas is to locate "an experienced parathyroid nography, parathyroid adenomas appear as oval, surgeon." oblong, or bulbous lesions with echogenicity less Proponents of preoperative localization of para- than that of the thyroid gland (Fig. t;.s0,u Using thyroid adenomas even in unoperated cases cite high-resolution ultrasound in a study of more than (1) the need for only unilateral dissections when an 150 patients, a sensitivity of 64Vo and specificity adenoma is evident on imaging; (2) the identifica- of 94Vofor adenomas and hyperplastic glands was tion of ectopic adenomas preoperatively, allowing achieved.5eOf those glands greater than 1 g in size, better planning and patient education; (3) detection ultrasonography had a detection rate of 95%.seOther of other head and neck masses that mav reouire investigators also quote sonographic sensitivities of treatment at the same time (e.g., thyroid masies); and (4) the reduction in operating room time, recur- rent laryngeal nerve paralysis, and postoperative hypoparathyroidism when preoperative imaging is performed.38'43'63'6'86In two studies bv Russell and tasas and their colleagues, the differ6nce between mean operating times with (71 minutes and 135 minutes) and without (97 minutes and 180 minutes) preoperative imaging justified the cost of the im- aging test.8'63The operative success rate also im- proved from 90% to 1,00Vowith preoperative im- aging.8 Uden also noted that the time for surgery and anesthesia decreased with preoperative im- aging; however, when a cost-benefit analysis was performed, he found that the cost of the imaging procedure outweighed its benefit.8TA reduction of 28 minutes of operating room time in the study by Roe and colleagues did not justify the $901 mean cost of localization.62 Other surgeons take a centrist position regarding bilateral or unilateral neck ex- plorations. They perform unilateral neck dissections if imaging studies are definitive but convert to bilat- eral surgery if (1) imaging is equivocal or shows multifocal abnormality, (2) more than one enlarged gland is identified at surgery, (3) the patient has a multiple endocrine neoplasia (MEN) syndrome (often associated with parathyroid hyperplasia), or (4) a unilateral exploration is unrevealing.63 When a parathyroid adenoma is not identified in a stereotypical perithyroidal location, the surgeon may empirically explore the anterior mediastinum, Figure 1. Ultrasonogramof parathyroidadenoma. Deep deep cervical space, periesophageal grooves, or ca- to the thyroid tissue, one can see a hypoechoicmass rotid sheath region. The yield of surgery in this (arrows)representing a parathyroidadenoma. 438 YOUSEM

60Vato 707o and specificities in the range of 907a to It is not necessaryto sacrificeaccuracy with the 967a.20,21,36,n simpler sestamibi study. The overall sensitivity of When Stark and colleagues compared the accu- thallium-ee'Tc pertechnetatesubtraction scintigra- racy of high-resolution CT with ultrasonography phy for parathyroid adenomadetection (75-85Vo1z'sz for detecting parathyroid adenomas, they found the is substantially less than that of ee'Tc sestamibi, sensitivity of CT to be 70% with a specificity o{ which runs in the range of 90%to 100%.2e,33,53.54.80 90Vo,77an improvernent over their experience with No thallium-positive adenomas have been sesta- ultrasonography. Sommer and colleagues also mibi-negative to date. Furthermore, in a compara- found CT to be more accurate than ultrasonography tive study of nonoperated patients, Kneeland and by over 10%; combining the studies yields a detec- colleaguesfound scintigraphy (82Vo)to have higher tion rate of 89% in patients without previous sensitivity rate than MR imaging (74%),CT (74%), surgery.'" and ultrasonography (59%).36The differenceswere Spritzer and co-workers were among the first to only statistically significant between scintigraphy report on the accuracy of MR imaging (Fig. 2) in and ultrasonography. detecting parathyroid adenomas.T6 Seventeen pa- When Price reviewed the presestamibiliterature tients had adenomas, and MR imaging correctly up until 1993 Q43 to 1785-cases).he found that identified 14 of them (82.3Va). Two false-positive MR imaging had the highest sensitivity rate for the and three false-negative studies for adenomis were detection of adenoma (74%) followed by nuclear reported; given the possibility of 72 glands, this medicine studies (72%),CT (65%),and ultrasonog- yields an MR accuracy of 92% for adenomas. raphy (63%).58The false-positive rate of nuclear The numerous options for nuclear medicine scan- medicine (.1.Vo)was lowest compared with MR im- ning for parathyroid adenomas stem from the fact aging (14%),CT (16Vo),and ultrasonography (187"). that there are no agents that are exclusively taken up Sestamibi data over the past 2 years suggest that by the parathyroid glands or adenomas. Therefore, it surpassesall other techniquesin sensitivity and agents that are taken up by parathyroid adenomas accuracy. Unfortunately, the high rate of thyroid and the thyroid glands (thallium and ee^Tcsestam- abnormalities (40-487") that coexist with parathy- ibi) must be subtracted from those that are only roid adenomas may lead to false-positive scinti taken up by the thyroid glands (ry*Tc pertechnetate grams becausethyroid lesions may concentratera- and 123I)(Fig. 3). This then allows visualization of diotracers to the same degree as parathyroid abnormal uptake by parathyroid adenomas. Com- adenomas.as,53,saReports of ee*Tcsestamibi uptake puter processing is required to enhance accuracy in thyroid cancersand their nodal and distant me- with subtraction techniques.2 At most centers, how- tastasessignal the possibility for false-positivestud- ever, ee^Tcsestamibi imiging is performed without les.'' '" subtraction. Ten to thirtv mCi of ee-Tcsestamibi are injected with scanning a1 1S-minute intervals for up Parathyroid Hyperplasia lo 2 to 4 hours after iniection.aT Because the agent washes out of the thyroid gland rapidly but iJ re- Approximately 30%of patients with parathyroid tained by parathyroid (and thyroid) adenomas, de- hyperplasia have familial hyperparathyroidism, in- Iayed images are all that are usually necessary for cluding variants of the multiple endocrineneoplasia good localization (Fig. 4). (MEN) syndromes (Table 2). As noted earlier, hy-

Figure 2. A and B, MR imagesof parathyroidadenoma. A, A small soft tissuenodule (arror,rr) is seen adjacentto the trachea locatedbelow the thyroid gland on the right side. This was a parathyroid adenomain a low perithyroidallocation. A Aftergadolinium injection, the lesion(arrow'1 enhances avidly. PARATHYROID AND THYROID IMAGING 439

'4. .. :;:-',1. i" .,*

Figure 3. Thalliumsubtraction study. The thalliumscan (top left) can be sequentiallysubtracted from the technetiumpertechnetate scan of the thyroidgland (fop right).On the lower set of images,note howthe thyroidgland uptake is eliminatedallowing visualization of the inferiorpole parathyroid adenoma on the left (arrows\.

Figure 4. A and B, se'Tcsestamibi scan of a parathyroidadenoma. A, Initialtechnetium-ggm sestamibi scan of the parathyroidregion demonstratesuptake in the thyroidgland and parathyroidadenoma (arrows)"B, On delayedimaging, the thyroiduptake has washedout, whereas the parathyroidadenoma (arrow\has persistenttracer accumulation. 440 YOUSEM

Table2. MULTIPLEENDOCRINE NEOPLASTA (MEN) SyNDROMES Feature MEN I MEN IIA MENIIB Eponym Wermer Sipple Mucosalneuroma syndrome Parathyroidabnormality Hyperparathyroidism(90%) Parathyroidhyperplasia in Very rare due to hyperplasiamore 20-300/0 commonlythan adenoma Thyroidlesion Goiter,adenomas, Medullarythyroid carcinoma Medullarythyroid carcinoma thyroiditisare rare Pituitarylesions Adenomas(20-30"/.) No No No Yes Yes Other manifestations Pancreaticislet cell Mucocutaneousneuromas adenomas( or Marfanoidfacies )30-35% Cafe au lait spots Adrenalcodex adenomas or carctnomas Rarelyglucagonomas, VlPomas,carcinoid Zollinger-Ellisonsyndrome Chromosomallinkage A-D chromosome11 A-D chromosome10 A-D. chromosome10

perplasia accounts lor 727oto 75% of patients with 7% to 2%, although causes hyperparathyroidism. hyperparathyroidism in 85Va to 90Vo of cases.3e,ao CT is- Leported to have a sensitivity rate of 457o Metastases to lymph nodes occur in one third of to 88%s'! ultrasonography, 307oto 697o20,21,35,58,n.cases,and distant metastasesin27Vo to287a ofpa- and MR imaging, 40Voto 63Va58'76for detecting hy- tients. Men and women are affected eouallv. perplastic glands. Parathyroid hyperplasia is de- Edmonson and colleagues noted thai a paratny- tectedin43% to 657oof cases with thallium subtrac- roid carcinoma may have the same sonographic ap- ee-Tc s8'e3 tion and 55% to 75% with sestamibi.20,21,53, pearance as a benign large adenoma (hypoechoic The added accuracy in identifying hyperplastic with or without heterogeneity); only the presence glands has led to a growing consensus in support of local invasion into the thyroid gland, muscles or ee^Tc of the use of sestamibi as the optimal agent vessels, or nodal metastases would suggest this di- for p-alathyroid adenoma and hyperplasia localiza- agnosis.l3 80 tion.53,54 Parathyroid carcinomas have been reported to oo'Tc accumula te sestamibi.L al Parathyroid Carcinoma

Of all patients with hyperparathyroidism, the in- Reoperation for Hyperparathyroidism cidence of parathyroid carcinoma (Fig. 5) is only During reoperation of previously operated cases, 307o to 75% of abnormal parathyroid glands are found in a perithyroidal location, presumably overlooked or missed during the initial opera- tion.12'4s'46'61Parathyroid adenomas in patients who have failed initial operation are located in the ante- rior mediastinum in 20Voto 38V0,in a paraesopha- geal or deep cervical location in approxim ately 20Va, intrathyroidal in 8Vo, and parathymic in 2Vo.45'46' 61 Supernumerary adenomatous glands are present in 15% of cases.Of those located in the chest, posterior mediastinal ectopic adenomas are one-fifth as com- mon as anterior ones.s The risks associated with reoperation outweigh the cost of preoperative imaging. In those patients who are reoperated, the risk of vocal-cord injury because of damage to the recurrent laryngeal Figure 5. MR imageof parathyroidcarcinoma. A largesoft nerv-e tissuemass (arrows)is seen anterolateralto the trachea or vagus nerve is approximately 77o compared with on the leftside. The massseems to be invadingthe inferior the initial operating room risk of 1..3%.a6When im- platysma-sternocleidomastoidmusculature and invadesa aging is not performed prior to reoperation for hy- jugular vein (J). Histopathologically,this was a parathy- perparathyroidism, surgery is approximately 60Vo roid carcinoma. to707o successful; when imaging is performed prior PARATHYROID AND THYROID IMAGING 441 to reoperation, the success rate increases to 80% creases the reoperation success rate by more than to 90%.58In reoperated cases, the sensitivities of 30%.16 ultrasonography (36-7 6V"),'n'45'58' 77 scintigr aphy (26- g0vo), z+, +s,so, sacT (45_ 63%),24,4s,s8, 77and MR imaging (50-91Vo)'n'"'n5'56's8have ranged widely. In a review Secondaryand Tertiary of the literature, Price concluded that MR imaging Hyperparathyroidism was the best cross-sectional imaging study to per- form in this scenario, and nuclear scintigraphy the The evaluation of patients with secondary or best functional examination.s8 The latest figures on tertiary hyperparathyroidism is rarely centered sestamibi scintigraphy have shown sensitivities in around the parathyroid glands becausethe kidneys the range of 80% to90Vo.a1'e2Parathyroidhyperplasia arethe sourceofabnormality in thesediseases. Para- is the most difficult diagnosis to make and accounts thyroid glandular hyperplasia usually occursin as- for most false-negative studies.al e2 Nonetheless, sociationwith chronic renal failure and renal osteo- Majors and colleagues found that sestamibi scan- dystrophy. e-Tc sestamibihas been able to identify ning identified parathyroid tissue in all nine pre- bilateral uptake in hyperplastic glands and residual viously operated patients, including one with para- parathyroid tissue in those individuals treated sur- thyroid .*t gically in the neck for secondary hyperparathy- By combining ultrasonography, CT, and scintig- roidism.e3 raphy, one can increase the sensitivity rate to 78%, but at a high cost.asAlthough more invasive studies have a greater yield, they are more demanding. Therapeutic Techniques Miller and colleagues' study found parathyroid ve- nous sampling (80Vo),intraoperative ultrasonogra- Ethanol ablation of parathyroid adenomas has phy (787"), and arteriography (49-60Vo) Io have beenperformed under ultrasound guidanceby per- higher sensitivity rates than the noninvasive im- cutaneousinjection of absolute ethanol.sl'71' 8e This aging studies.aaThe expense and technical difficulty technique may be used in patients with primary or in performing these invasive examinations pre- secondaryhyperparathyroidism who are not surgi- cludes their routine use, but they may be held in cal candidatesbecause of medical illnesses.Approx- abeyance for cases with equivocal or nonrevealing, imately 0.5 mL to 1 mL of ethanol (95Vo)may be noninvasive sfudies. injected at multiple sites within an adenoma with In the patient who has failed prior surgery for a a22-gaugeneedle. The successof this techniqueis parathyroid adenoma, both imaging and surgery monitored by following serial serum calcium levels; must contend with scar tissue in and around the the techniquemay be repeateduntil normocalcemia thyroid glands, a loss of tissue planes, postoperative is achieved. inflammation, lymphadenopathy simulating para- thyroid adenomas, and distortion of landmarks. False-negative scans (caused by obscured anatomy) Parathyroid Cysts tend to occur in the perithymic or perithyroidal operative beds. The incidence of false-positive ex- Cysts of the parathyroid glands are more com- aminations (usually caused by lymphadenopathy) mon in women than in men and mav be present is lowest with nuclear medicine studies, followed in the neck (Fig. 6) or anterior mediastinum. At by MR imaging, ultrasonography, and CT according presentation, they may be very large in size, and to Miller and colleagues.as the differential diagnosismay include thyroid cysts, Therefore, which study should one perform in the thymic cysts,and necrotic lymph nodes. They usu- previously operated patient? Two camps of opinion ally arise in the region of the inferior pole of the have formed. Sestamibi scintigraphy is probably the thyroid gland. They are virtually never found in most accurate and affordable studv currentlv avail- children; most casespresent in the fourth and fifth able to identify parathyroid adenomas; its disad- decade of life.a0They are usually unilocular, large, vantage is that the surrounding anatomy is not visu- and may have hyperproteinaceouscontents yield- alized for surgical orientation. It alone or combined ing high intensity on Tl-weighted MR scans.The with ultrasonography or CT is an effective option. etiology may be congenital becauseof remnants of Alternatively, the most accurate (and most expen- pharyngeal pouches, or cysts may develop from sive) cross-sectional imaging technique is MR im- degeneratedparathyroid adenomas. aging, which provides good anatomic detail, al- though it has the small risk of mistaking a lymph node for an adenoma. Because re-reoperation is an Hypoparathyroidism anathema to the surgeon, multiple studies are not uncommonly performed if one is not definitive. The The most common causeof hypoparathyroidism idea of using a morphologic test (CT, ultrasonogra- is iatrogenic removal of all functioning parathyroid phy, or MR imaging) and a functional test (ee-Tc tissue during surgery for hyperparathyroidism or sestamibi) is appealing. Use of this algorithm in- thyroid disease.Primary idiopathic hypoparathy- 442 YOUSEM

Figure 6. A and B, MR images of parathyroidcyst. A, CoronalT1-weighted scan demonstratesa roundedcystic mass (arrows)with low intensityfluid. @ The cyst (c) is brighton axial T2-weighted scan. This patientis status posfthryoidectomy.

roidism is a disease of childhood unassociated with the deep cervical fascia.The thyroid isthmus is the cervical abnormalities. Pseudohypoparathyroidism midline portion of the gland and from it may arise may be caused by renal disease; the serum parathor- a pyramidal "lobe" (50-807, of patients) lying su- mone (PTH) levels are paradoxically high because periicial to the thyroid cartilage.;" of a lack of renal responsiveness to the hormone. The vascular supply to the thyroid gland is de- The glands may be normal or hyperplastic. In pseu- rived from paired superior thyroidal arteries dopseudohypoparathyroidism, the calcium and (branchesof the external carotid arteries) and infe- phosphate levels are normal, although the physical rior thyroidal arteries(branches of the thyrocervical features of pseudohypoparathyroidism (coarse fa- trunks of the subclavian arteries). The inconstant cies, dwarfism, mental retardation, round face, thyroidea ima arises directly from the aortic arch stubby fingers) may be present. and supplies a small inferior portion of the gland. Imaging of parathyroid glands in patients with The thyroid gland drains into superior, middle, and hypoparathyroidism is limited to the surveillance inferior thyroidal veins,which passto internal jugu- for congenital absence, which is best accomplished lar and brachiocephalic veins. Vagal and sympa- with scintigraphic methods thetic plexus branchesprovide innervation. Histologically, the gland contains follicular cells that secretethe thyroid hormonesand parafollicular THYROID IMAGING ("C") cells that elicit thyrocalcitonin. Interspersed within the gland one finds fibrous septa arid col- The thyroid gland offers a multitude of interest- loid deposits. ing pathologic entities and lends itself to many dif- ferent imaging modalities. Depending on the clini- cal presentation and suspected abnormality, the lmaging Features of Masses clinician may order nuclear medicine scintigraphy, ultrasonography, CT, or MR imaging. The evalua- Ultrasonography tion of an infant with a midline cystic mass in the lower neck is entirely different from that of a The main role of cross-sectionalthyroid imaging 40-year-old man with a solid palpable nodule in (ultrasonography, CT, MR) is to evaluate thyioid the thyroid gland. Once the anatomy and imaging massesfor_potential malignancy. Ultrasonogriphy, options available to study the thyroid gland are becauseof its simplicity, low cost, and adility to understood, it is useful to divide thyroid lesions distinguish cystic from solid lesionsis often theiirst into neoplastic, congenital, and inflammatory cate- modality used to evaluate a thyroid mass in the gories. euthyroid patient. Good quality ultrasonography requirestransducers that have 7.5 to 10 MHz fre- quencies.2o,7EThese allow excellentdetail of the su- Anatomy perficial portions of the gland but enough penetra- tion to evaluateposteriorly to the level of the spine. The thyroid gland is positioned anterolateraland When a solid leiion is hyperechoic, the incidence superficial to the larynx and tracheaand is fixed to of malignancy is only 4%.72If a solid lesion is iso- the airway by fibrous septa.Although no true lobes echoic,the incidenceof malignancy incre asesto 26Vo of the gland exist, it is enveloped by portions of and, if hypoechoic,malignancy occursin 63%.72Pap- PARATHYROID AND THYROID IMAGING 443 illary carcinoma most commonly presents as a solid phy, it is usually becauseof the sclerosingform of hypoechoic (77Vo)or isoechoic (14%) mass with or papillary carcinoma or medullary carcinoma.r6 without calcification (calcifications are hvperechoic If the margins of tumors on ultrasonography are but cause acoustic shadowing that is hypoechoic) studied, 16% of malignant lesions will be found to (Fig. 7) .?'zIfa cancer is hyperechoic on ultrasonogra- have sharply marginated, well-defined borders,

Figure 7. ,4-C, Ultrasonogramsof papillarycarcinoma. A, A reasonablywell-defined soft tissuemass (M) is presentsurrounded by normalthyroid tissue. The mass is hypoechoic.Fine-needle aspiration revealedpapillary carcinoma. B, On transversesonographic images of a differentpatient, a softtissue mass (M) is identifiedthat has internalheterogeneity to its echotexture.This masswas also a papillary carcinomaof the thyroid gland. C, The longitudinalsonographic view of this mass (M) shows the absenceof an echopenichalo aroundthe lesionand ill-definedinferior borders (arrows\. 444 YOUSEM

whereas irregular or ill-defined borders occur in glands or to perform whole-body imaging after thy- approximately 60% of .T2Unfortunately, ir- roid ablation to detect metastatic foci of thyroid regular or ill-defined borders also occur in approxi- cancer. The other agents have energies of 140 keV mately 45Voof benign lesions.T2When a mass has a (ee-Tc)and 159 keV (123l).eo complete halo of echopenia around it, the lesion is The major role of scintigraphy in the evaluation twelve times more likely to be benign than malig- of a thyroid mass is the determination of whether nant. If the halo is incomplete, a benign etiology is the lesion is hot (more uptake than the normal thy- still approximately four times more likely than a roid gland), warm (some activity but not as much malignant one.72Lesions meeting the absolute crite- 2ts the normal gland), or cold (little to no uptake). ria for cysts (well-demarcated, smooth-walled, an- The risk of cancer in a hot nodule is between 1% echoic, and demonstrating enhanced through- and 4Vo, a warm nodule 8% and'l,jVo, and a cold transmission) are usually benign.t6 A cystic lesion nodule 15% and ZSVI(FiB. 9).se'0+,0tIn a patient who with punctate, calcified mural nodules is indicative has a prior historv of head and neck irradiation. the of papillary carcinoma (Fig. 8). risk oi malignanci itr a cold nodule doubles to 30% to 50%.58Cold nodules in men have a higher rate Nuclear Medicine of malignancy because women have a greater inci- dence of benign cold nodules from degenerated ad- A nuclear medicine studv may be another first- enomas. If one performs dynamic injection ee-Tc line imaging modality in a patieirt with a palpable pertechnetate scintigraphy, one may find that hypo- thyroid mass. The agents used for thyroid imaging perfused lesions (less vascularity than that of native include 123I,131l, ee'Tc pertechnetate, and 201T1.The thyroid gland) are virtually never cancers, whereas half-lives, whole-bodv radiation doses, and thvroid most malignancies are "euperfused" or hyperper- radiation doses are listed in Table 3.5&e0 Scanning fused.35 Increased thallium uptake on both earlv is performed 15 minutes after administration of and delayed scintigrams also iras been anecdotally 5 ti, 10 mCi of ee'Tc pertechnetate, 4 to 24 hours reported in thyroid malignancies.ra after administration of 100 to 400 p.Ci of 123Iiodine, Rarely, a lesion is cold on 123Iscintigraphy but and 24 to 72 hours after administration of 30 pCi hot or warm on a e-Tc pertechnetate scan (a "discor- of r31Iagents. With 'zolTl,scanning is performed 5 to dant nodule"). It is beiieved that this phenomenon 10 minutes after thallium administration. Because is caused by a lesion that traps iodine (assessedwith the radiation energy of 131Iis so high (364 keV), it is pertechnetate) but does not organify it (the iodine the preferred agent for imaging substernal thyroid scan). The differential diagnosis includes malig- nancy/ goiter, or follicular adenomas. Often, a bi- opsy is required in this situation.

Computed Tomography The presence of calcification, cysts, hemorrhage, hypodensity or hyperdensity, or well-defined bor- ders in a solitary mass on CT does not exclude a carcinoma (Fig. 10). Peripheral eggshell-like calcifi- cation and large multiple chunks of calcium suggest benignity, whereas fine punctate calcification is more indicative of malignancy.60 Calcification oc- curs in 13Voof all thyroid lesions, including 17% of all malignancies and 1,1,%of all benign processes.T2 Similarly, cystic areas occur in many thyroid masses; 38% of malignancies have cystic compo- nents, and 62Vo of benign masses may be entirely or partly cystic.72Hemorrhage may be found in pap- illary carcinomas or goiters. Multiplicity of nodules in an enlarged thyroid gland usually suggests a benign process (or metastases). The presence of lymphadenopathy or infiltration of adjacent tissues suggests malignancy. More than 50Vo of patients with papillary carcinoma have nodal spread at presentation, and 22Vohave occult Figure 8. Cyst and nodule.The ultrasonogramshows a thyroid tumors.a Curiously, the lymph nodes of thy- cyst with a nodule (arrow) protruding into the cyst. Note roid papillary carcinoma may show calcification, the throughtransmission(arrowheads) from the cyst.This cyst formation, colloid accumulation, hemorrhage, was a colloidcyst with benignnodule. Calcification of the or necrosis.T3'7aSometimes the wall of a cystic node muralnodule would make papillary carcinoma more likely. may be unidentifiable, thereby simulating a PARATHYROID AND THYROID IMAGING 445

Table3. SCINTIGRAPHICAGENTS USED FOR THYROID IMAGING Agent Half-life Total Body Dose (rads) Dose to Thyroid Gland (rads) Dose Administered t-123 13.6h 0.03 2-8 100-400pCi PO t-125 60.1d 0.29 80-450 30-1 00 pCi l-131 8.05d 30-100 30-100 pCi PO Tc-99m 6.02h o.02 0.04-2.0 5-10 mCilV Tr-201 3d 0.21 o.92 2-3 mOi lV

h : hours;d: days;PO: oral;lV = intravenous;Ci : curies.

branchial cleft cyst. Papillary carcinoma of the thy- malignant lymphadenopathy. Irregular margina- roid may metastasize to posterior triangle, subman- tion and clustered nodularity is characteristic, but dibular, retropharyngeal, or jugular chain lymph not specific for carcinomas (Fig. 11).18Lesions that nodes.73'74The nodes mav enhance uniformlv and have an intact and symmetric pseudocapsule are dramatically or, as with cystic or calcified nodes, usually benign, whereas those with pseudocapsules not at all.73,7aAny lymph node seen in a patient with that are penetrated or destroved are usually can- papillary carcinoma is suspected of being malig- cers.18'52Lesions that have capsules with irrbguhr nant, no matter the size because of the relatively thicknesses may be malignant or benign. On MR high rate of lymphatic spread. imaging, the nodes of papillary carcinoma may be Enhanced CT has a maior drawback in the evalua- bright or dark on Tl-weighted and T2-weighted tion of thyroid lesions. Because of the iodine uptake scans, possibly related to the presence of intranodal from the contrast agent, thyroid localization with hemorrhage or colloid accumulation. nuclear scintigraphy and radioactive iodine treat- Postoperatively, thyroid carcinoma recurren- ment must be delayed 4 to 8 weeks after administra- ces are usually medium to high intensity on T2- tion of iodinated contrast agents. weighted scans, whereas scar in the operative bed is usually low intensity.l Postoperative edema, in- fection, or hemorrhage may simulate recurrent tu- MR lmaging mor. 131Iscintigrams are the best modality to evaluate Histologic specificity of thyroid lesions is not im- the operative bed and to screen for distant metasta- proved with MR imaging. The key to the diagnosis ses aiter thyroidectomy. MR imaging, in conjunc- of at MR imaging is the presence of tion with 131Iradioisotope scanning, has been recom- mended for confusing postoperative cases.6

Fine-Needle Aspiration Intimately associated with any imaging technique is fine-needle aspiration cytology. Many palpable lesions of the thyroid gland may be aspirated with- out imaging, but ultrasound is the most common modality used to guide aspirations because it im- ages in real time. Aspiration cytology in skilled hands yields outstanding results. In a series of 11,000 guided and unguided samples performed at the Mavo Clinic. the sensitivitv of the technioue was found io be 98% with a 99% positive pr"di.tin" value for cancer.le Nondiagnostic specimens were present in21% of cases,however. Using fine needle aspiration with ultrasound guidance yields results of nearly 1,00%sensitivity and specificities near9}Vo, while reducing nondiagnostic samples.l6

Malignancies of the Thyroid Gland

Thyroid cancers are a mixed group of lesions. Figure 9. Cold noduleon scintigraphy.This ee'Tcpertech- The most common histologic subtype is papillary netate scan demonstratesa cold (arrows) carcinoma that accounts for 55% to 80% of thyroid nodule in the 58'78 lateralaspect of the leftthyroid gland. A solitarycold nodule malignancies.3e' Although follicular elements in such as this one has a 15% to 25% chanceof beino ma- a papillary carcinoma are common, and this has lignant. led to a "mixed papillary-follicular" or "follicular 446 YOUSEM

Figure 10. A and B, CT scans of papillarycarcinoma. A, This enhancedCT scan demonstratesa mass (M), which has irregularcalcification within it, in the left side of the thyroidgland. The presence of lymphnodes (arrouvs) is highlysuggestive of papillarycarcinoma. & This cysticlesion with peripheral calcificationin the wall (arrowyproved to be a degeneratedadenoma.

Figure 11. A-D, Papillarycarcinoma on MR scans and scintigraphy.4, Axial T1-weightedscan demonstratesa hyperintensemass (M) with peripheralhypointensity representing calcification. The wafl, however,is not intact at its anterior-mostborder (arrows\.The remainderof the gland shows diffuseenlargement with heterogeneoussignal intensity compatible with goiter.The patientpresented with an enlargingright-sided thyroid mass. 4 Post-gadolinium-enhancedscan demonstratesminimal enhancementbecause it was bright on pregadoliniumT1-weighted scans. No invasionof adjacent structureswas identified.C On T2-weightedscan, the border,though irregular,seems to be intact. Note that on the left side, the signal intensityof the goiterousthyroid gland is inhomogeneous. D, Scintigraphyof this mass revealedbilateral cold areas (C) within the thyroidgland with onlya central area (arrows)of relativelynormal uptake.Biopsy revealedpapillary carcinoma of the thyroidgland. This shows how a benignappearance can be presentwith malignanciesof the thyroidgland. PARATHYROID AND THYROID IMAGING 447 variant" histologic classification, the "mixed can- lary carcinoma. No distinguishing features on im- cer" ultimately behaves like a papillary carcinoma aging studies suggest this diagnosis as opposed to (vide infra). Purely follicular carcinoma occurs other cancers, although, on ultrasonography, follic- in 5% to 15%. Anaplastic carcinoma represents 3% ular carcinoma is isoechoic in 52% and hypoechoic lo 10% of all malignancies, with m-edullary or in44Vo.20'72Compared with papillary carcinoma, fol- Hurthle's cell carcinoma accounting for 4Vo lo licular carcinoma rarely becomes cystic and more 5Vo.1e'3eMedullary carcinoma may present in associ- frequently invades vessels.3e ation with the multiple endocrine neoplasia syn- dromes (see Table 2) and serologically may express Anaplastic Carcinoma . The other histologic diagnoses to con- This type cancer is of the most sider in thyroid malignancies are non-Hodgkin's of one aggressive head neck with and metastases. malignancies of the and prognoses marked months rather than years. Older patients Imaging has a well-defined role in the workup in are usually affected. Anaplastic thyroid carcinomas of the patient with a solitary nodule in the thyroid occur within substrate goiters in 47Voof cases3e gland. Unless a classic appearance of a benign con- a of and often coexist with other forms of better differen- dition is present, however, pathologic sampling is tiated thyroid cancer. The in mixed tumor required. This is because the appearance of thyroid outcome cases is dominated by the poor prognosis of ana- malignancies may simulate many benign processes, carcinoma. and vice versa. The specificity of imaging findings ^r:lastic is low. On ultrasonography, these carcinomas are most whereas on The detection and characterization of a thyroid commonly hypoechoiq20,D,72 CT, ana- plastic carcinomas show of dense neoplasm is not the only role of imaging. Imaging evidence amor- should also evaluate for infiltration of the adiacent phous calcification in SBVoof cases and necrosis in 74Vo.u lymph present in 74Vo soft tissue, aerodigestive tract, paraspinal muscula- Metastatic nodes are to 80% of and show necrotic areas the ture, and carotid arteries. The presence or absence cases 50% of time.e'82 Invasion into arteries of adenopathy is also important for prognostic im- carotid or adjacent in 34% plications with thyroid cancer. aerodigestive structures occurs to 55% of patients, and in 25Vo the primary tumor extends into the mediastinum (Fig. 13).q8'?Rapidgrowth and PapillaryCarcinoma obliteration of adjacent tissue planes are hallmarks of this deadly tumor with a median The presenceof psammoma bodies (laminated survival of 7 months. calcific spherulesin25-40Vo of cases),ground glass approximately nuclei, and a branching pattern with a fibrovascular papillary stroma are the histologic signatures of Medullary Carcinoma papillary carcinomaof the thyroid gland.3eAs noted Medullary carcinoma originates in the parafolli- earlier, follicular growth patterns may coexist.Cyst cular or "C" cells of the thyroid gland, cells derived formation (cystadenocarcinoma), encapsulation, from neural cresttissue in the ultimobranchial bod- multifocality, and anaplasiamay be present within ies of the branchial pouch system.These cells nor- a thyroid gland with papillary carcinoma. mallv secretethvrocalcitonin, which decreasesse- Papillary carcinoma is the thyroid malignancy rum'calcium. Eiahty percent to 90% of medullary that has the greatestlikelihood of spread to lymph carcinomasexpress calcitonin. Functioning tumors nodes; the nodes may be tiny, cystic, hemorrhagic, have a better prognosis.q or calcified(Fig. 12).The incidenceof nodal metasta- Medullary carcinomasare usually hypoechoicon sesduring diagnosisis50%, whereas distant metas- ultrasonographyzo'zz' 72; however, echogenic foci tasesare reported to occur in 4Vato 7Vo,usu.ally to causedby deposits of calcium may be seenwithin the lungs, bone,or central nervous system.3eDespite these tumors and metastatic lymph nodes when thesefeatures, the 2O-yearsurvival rate is reported present.22These tumors usually do not take up io- to be as high as 90%. Approximately 10% of papil- dine but may be thallium or gallium avid. Somato- lary carcinomasare bilateral.ea statin receptor scintigraphy also may detect medul- lary carcinoma.llThe tumor is solid on CT and MR imaging and spreadsto lymph nodes in more Follicular Carcinoma than 50Vaof cases(Fig. 14). Pure follicular carcinomais relatively uncommon Medullary carcinoma has a familial incidence of when the follicular variant of papillary carcinoma "lOVoto 20Vo.Sipple syndrome is the associationof is excluded. The tumor mav be diffuselv invasive medullary carcinomawith pheochromocytomaand or well encapsulated.Follicular carcinornaless fre- parathyroid adenoma or hyperplasia. This is also qently spreadsto lymph nodes (2-10%) than does known as the MEN 24. When mucosal neuromas papillary carcinoma, but disseminates hematoge- and marfanoid facies coexist,MEN 28 is said to be nously more readily.3eThe prognosis depends on present (see Table 2). Both syndromes have been the presenceof hematogenousmetastases or local localized to an abnormal gene on the tenth chro- invasivenessbut is not asoptimistic asthat for papil- mosome. 448 YOUSEM

Figure 12. 4-E, Metastasesof papillarycarcinoma. A, This postcontrastaxial CT scan shows two hypodenselymph nodes (n) on the right side of the neck from papillarycarcinoma" 8, Note that the patienthad diffuse metastases to the lungsrepresented by multiplemiliary-like nodules. C, In a different patient,a denselyenhancing lymph node (n) on the left side is seen deep to the sternocleidomastoid muscle.D, This patienthad a cysticand sotidfymph node metastasis(arrows) from the primarythyroid carcinoma(c). E, T1-weightedMR scan showsa hyperintensenode (arrow) from colloid,hemorrhage, thyroglobulin,or highprotein.

Lymphoma are usually hypoechoic at sonogra- z-zt2 phy-z0 Lymphoma is iold bn technetium or"io- may present as a solitary dine nuclear medicine studies; however, gallium mass(80%) (20%).81 or asmultiple nodules An ante- scans may show increased activity. Other lympho- cedent history of Hashimoto's thyroiditis in an el- proliferative (leukemia) and granulomatous'dis- derly female with a rapidly enlarging, compressive, eases (e.9., sarcoidosis) also may be gallium avid and infiltrative mass suggests lymphoma. Most and are in the differential diagnosis. The tumor is are B-cell neoplasms.3eResponse to chemotherapy hypodense on unenhanced and enhanced CT stud- and radiation is variable; some patients do very ies and shows necrosis or calcification in only 7% well. of cases (Fig. 15).81Invasion of the carotid sheath PARATHYROID AND THYROID IMAGING 449

Figure 13, Anaplasticcarcinoma on CT scan. Diffuseen- Figure 15. CT scanof thyroidlymphoma. Diffuse infiltration largementwith inegularcontrast enhancement is notedin of the leftthyroid gland is notedon this contrast-enhanced the thyroidgland of this patientwith anaplasticcarcinoma. examinalion. The predominantdensity is hypodenseto the nativethyroid tissue.One would expectto see markedenhancement in the normalthyroid gland due to iodineaccumulation. chogenic carcinoma and renal cell carcinoma. Multi- focality is the norm (Fig. 16), and hemorrhage is (19-51,7") or metastases to lymph nodes (1,4-44Vo) not uncommon with renal metastases. are not uncommon.8l The absence of calcification and necrosis, the rarity of invasion into surrounding soft tissues, and the lower incidence of nodal dis- BenignMasses semination help to distinguish lymphom a fuom ana- r:lastic^ carcinoma. Fu nction ing Thyroid Adenom as Lymphoma is usually homogeneously hyperin- tense on T2-weighted MR scans. Although some More than ninety percent of solitary hot nodules workers have found Hashimoto's thyroiditis to be on scintigraphy are benign in etiology, usually ade- low in intensity on T2-weighted images and, there- nomas or hyperplasias that are expressingthyroid fore, distinguishable from lymphoma (which is hormone.Plummer's diseaseis hyperthyroidism re- bright),6e most investigators have found their signal sulting from a solitary autonomoushot nodule (Fig. intensities to overlap.18,55' 57 17).58The difference between an autonomous and a hypertrophic functioning hot nodule depends on the response thyroid test. Metastases to a suppression After a diagnostic course of thyroid hormone administra- Metastasesto the thyroid gland are often clini- tion (with confirmation of depressedthyroid stimu- cally occult. Pathologicallp metastasesto the gland Iating hormone [TSH]), a lesion that is persistently may be present in2% to 4Voof patients dying from hot on a eemTcpertechnetate scan is considered an malignant disease.66The two most commonprimary autonomouslesion, whereasone that becomescold tumors to metastasizeto the thyroid gland are bron- is considered hypertrophic.unOther sourcesof hot

Figure 14. A and B, Medullarycarcinoma of the thyroidgland. l, This patienthas a thyroidmass (.) on the rightthat has invadedthe trachealwall accountingfor the thickening(arrows) seen lateralto the endotrachealtube. lt was medullarycarcinoma. B, Note absence of right lateraltracheal wall furtherdown. 450 YOUSEM

rithm. The majority of cold nodules are causedby degenerated(follicular) adenomas(Fig. 18)nodular hemorrhage, cysts, goiters, inflammatory condi- tions (seesubsequent discussion), or amyloid depo- sition.6aFollicular adenomasoccur in all agegroups, in women more than in men, and are usually less than 3 cm in size.As adenomasoutgrow their blood supply, they may involute or encyst.Alternatively, they may develop intralesional hemorrhage (and acutely expand), necrosis,calcification, or scarring. Malignant degeneration is not believed to occur Figure 16. Metastaticrenal cell carcinomato the thyroid in adenomas. gland.The multiplemasses in this enlargedthyroid gland Hurthle's cell adenomas(which some investiqa- werecaused by metastasesfrom a primaryrenal cell carci- tors believe are malignant in character) are more noma. Becausethe thyroidgland absorbs so much iodin- variable in size and shape with less well-defined ated dye, they appearas fillingdefects amidst the gland. borders. Occasionallp one will find a hyperplastic ade- noma that is responsive to TSH in a patient with nodules include thyroiditis, normal variation in thy- Grave'sdisease. this appea.sas a cold nodule be- roid function, and ectopic tissue.58 causethe hyperthyroidism of Grave's diseasesup- TSH, "Toxic" adenomas rarely cause clinically appar- presses which in turn suppressesthe adenoma ent hyperthyroidism until they exceed 2.5 cm in on a nuclear medicine studv. This entitv is called r n Le size.16The patient usually presents with a slowly Ma i e- nhar t synd ro me.oa growing . The imaging features of toxic In one of the earliestarticles on the subiectof MR adenomas are nonspecific on nonscintigraphic mo- imaging, Gefter and colleaguesidentified adenoma- dalities. The lesions are usually solid and en- tous nodules as small as 4 mm to 5 mm in size.l8 hancing. They noted that follicular adenomas appeared as well-circumscribednodules with heterogeneousin- tensity, bright on T2-weighted images (Fig. 19). N onfu nction i ng Thy roi d Ade n omas A cold (nonfunctioning) nodule is approached Cysts more aggressively than a hot nodule because of the higher rate of malignancy, especially in young Most thyroid cysts actually represent degenera- women and in men of all ages. A biopsy or aspira- tion of adenomas.Cysts of any kind are anechoic tion is often required early in the diagnostic algo- or echopenic on ultrasonography, show a distinct back wall, and demonstrate enhanced through- transmission. They are low density on CT unless hemorrhagic or infected. The density and intensity of the cyst mav not simulate that of cerebrospinal fluid on CT ancitrrtR imaging becauseof the p.esen"e of hyperproteinaceouscolloid within the cyst. Col- Ioid cysts are characterizedby homogeneoushigh- signal on Tl-weighted scans6a;however, this finding is not specificto colloid cystsbecause areas of hem- orrhage, also bright on Tl-weighted scans,can be seen in goiters, adenomas,and traumatized cysts. Even thyroglossal duct cysts (vide infra) may be hyperintensebecause of high protein content.

Multinodular Goiter Another common palpable thyroid abnormality is the multinodular goiter. A goiter is simply an enlarged thyroid gland that may be seenwith hy- perthyroidism or hypothyroidism. In the United States,the common vernacular is to imply non- Figure 17. Hot noduleon nuclearscintigraphy. Note in- a tense update of radiotracerin this functioningadenoma toxic goiter when the term is used. A euthyroid (arrow).The remainderof the gland shows relativelylittle or hypothyroid goiter is the most common thyroid uptakeowing to the suppressionincurred by reducedTSH lesion in the United States.Patients, usually older from the outpouringof thyroid hormone by the "toxic women, present becauseof hypothyroidism, neck nodule." masses,or tracheal-esophagealcompression. In rare PARATHYROID AND THYROID IMAGING 45'],

Figure 18. A and B, Cold nodule.A, A cold nodulewas seen alongthe lateralaspect of the left side of the thyroid gland(arrow) on this anteroposteriorview. B, The MR scan demonstratestwo lesions on this slicethat were adenomasin a multinodulargoiter. In retrospect,the other lesioncould be seen posteriorlyon the obliquescintigrams. instances, a previously nonfunctioning multinodu- mixed solid and cystic zones within an enlarged, lar goiter evolves into one with hyperfunctioning nodular thyroid gland with or without calcification nodules and causes hyperthyroidism. The incidence is the characteristicappearance of a multinodular of carcinoma in a multiodular goiter is very low goiter (Fig. 21). (below 3%) and the characteristic appearance of multiple cold areas interspersed with hot areas in a large gland usually obviates the need for aggressive biopsy of a palpable nodule (Fig. 20).6aA large, These are rare neoplasms of the thyroid gland. dominant, hard, or growing mass amidst a goiter As in other locationsin the body, thyroid teratomas should probably still be biopsied (see Fig. 1).70 may demonstrate fluid, fat, c;lcificatiory and os- Nontoxic multinodular thyroid glands show min- seodental densities in various combinations. They imal to moderate heterogeneity with nodularity and usually occur in the midline. mildly increased signal intensity on T1-weighted s2 MR image.l& Hemorrhagic foci are noted in 60% Hyperthyroidism of cases and the lesions are often heterogenous on T2-weighted scans.s2Goiters usually dJnot have The three most common causesof hyperthyroid- pseudocapsules.s2 On CT and ultrasonography, ism are Graves' disease(diffuse toxic goiter), toxic

Figure 19. A and B, MR imagesof a thyroidadenoma. A, Note the inhomogeneoussignal intensity in this hemorrhagicmass (M) on this T2-weightedfat-suppressed MR scan. B, On T1-weightedscan, one sees high signalintensity within the centralportion of the mass. lt may be unclearas to whether this representscolloid material, hemorrhage, or hyperproteinaceoussecretions. The capsulearound the lesion(arrows) seems to be well defined,except at its anteromedialaspect. 452 YOUSEM

(Graves' with coexistentTSH-dependent nodules). The latter appearson scintigraphy as a gland with diffuse increased trapping of the radiotracer with superimposedcold nodules.If the TFTsare elevated but the RAIU is normal, one should consider Plum- mer's disease (hyperthyroidism due to a solitary autonomoushot nodule that suPPressesthe remain- der of the gland), Graves' diseasewith rapid iodine turnover, or a laboratory error.mIf TFTsare elevated but RAIU is depressed,the possibilitiesinclude sub- acute granulomatousthyroiditis, subacutelympho- cytic thyroiditis, postpartum thyroiditis, and . With thyroiditides, thyroid hormone may escaperuptured follicles leading to transient hyperthyroidism, although the damagedgland can- not concentrate iodine so the RAIU and thyroid scansshow depresseduptake.3o ri:rir::i"ll':'::' , i .. , ..,. Figure 20. Goiter.Nuclear scintigraphy demonstrates an Graves' Disease enlargedinhomogeneous thyroid gland. Multiple cold areas are presentas well as warm areas and hot areas within Graves' diseaseis the most common causeof hy- this gland. oerthvroidism. This disease affects women more iommonly than men and a familial tendencyis pres- ent. Patientsmay have heat intolerance,weight loss, multinodular goiter, and toxic adenomas. The toxic fatigue, insomnia, tremors, palpitations, increased adenomas (discussed earlier) are separated into thirst and hunger, and agitation. Exophthalmos those that are TSH-responsive (hypertrophic) or may be present, although thyroid eye diseaseneed TSH-independent (autonomous). Occasionally, in- not occur only in the setting of hyperthyroidism; it flammation of the thyroid gland (thyroiditis) pro- may be present post-therapy when the patient is duces a transient state of hyperthyroidism. On rare euthyroid or even hypothyroid. Blood testsare usu- occasions, ectopic thyroid tissue (lingual or ovarian) ally able to make the diagnosis of Graves' disease causes hyperthyroidism. becauseof the autoimmune phenomenon associ- Intenzo and colleagues have proposed a unique ated with the disease.Thyroid-stimulating immu- algorithm for evaluating a hyperthyroid patient.3O noglobulins, such as long-acting thyroid stimulator, If thyroid function tests (TFTs) are elevated and the simulate the function of TSH and causehyperthy- 24-hour radioactive iodine uptake (RAIU) is also roidism. On iodine scans,there is markedly elevated elevated (normal, below 357"), the differential diag- iodine uptake within a nonfocal, hot, enlarged thy- nosis is Graves' disease or Marine-Lenhardt disease roid gland.

Figure 21. Ultrasonographyand CT scan of goiter.A, This ultrasoundexamination reveals multiple nodules(arrows\ seen as hypoechoicareas within an enlargedthyroid gland. 4 In a differentpatient, one can see bilateralenlargement of the thyroidgland with a hypodensecentral area on the leftside and irregularityand inhomogeneityon the rightside. The glandis enlargedand, curiously, is predominantly posteriorto the airway. PARATHYROID AND THYROID IMAGING 453

In a patient who is hyperthyroid, scintigraphy tries. Other etiologies include the other chronic may be useful in distinguishing Graves' disease, thyroiditides. Postoperative and postradiotherapy which shows homogeneous diffuse intense uptake (131Ior external beam irradiation) patients also ac- (70-85%) from thyroidltides (FiB. 22). Thyroiditis count for more hypothyroid patients. It is common is less homogeneous and the uptake may be normal, for patients treated with radioactive iodine for hy- high, or low depending on the state of the inflam- perthyroidism to become hypothyroid after sev- matory process. Because some thyroiditides (see eraryears. subsequent discussion) may revert to euthyroid ac- Congenital hypothyroidism occurs more com- tivity with time, the implications for theiapy are monly in the Japanesepopulation (1 in 5500 new- important; Graves' disease requires antithyroid borns).83Possible causes include thyroid aplasia, medication, radioactive iodine obliteration of the hemiaplasia (the left gland is absent more com- gland, or surgery. Thyroiditides are treated conser- monly than the right), or ectopia (80%),dyshormo- vatively. nogenesis(10-1,5%), pituitary or hypothalamic de- Diffuse glandular enlargement with avid en- ficiency (< 5%) and autoimmune disease(< SVo). hancement may be noted on CT and MR imaging Prompt replacementof thyroid hormone is critical in patients with Graves' disease. A large pyramidal becausemental retardation is a possible complica- lobe often coexists. Carcinoma of the thyroid gland tion of undiagnosed neonatal hypothyroidism.83 in a patient with Graves' disease is rare, reported Both ultrasonography and scintigraphy are used to in only 0.157oto 0.5Voof patients.l0 identify thyroid tissue in this population.

Hypothyroidism Congenital Lesions Hypothyroidpatients have cold intolerance;fa- tigue; apathy;weight gain;bradycardia; constipa- Thyroglossal Duct Cysts tion; edema; macroglossia; and poor condition of Two of the most common congenital abnormali- the hair, nails, and skin. Women are affected more ties associatedwith the thyroid gland are thyroglos- frequently than men. The response to thyroid hor- sal duct cystsand lingual thyroid glands.The thyro- mone replacement is excellent. glossal duct cyst is a congenital lesion in which the Hashimoto's thyroiditis is the most common tract of migration of the thyroid gland from the cause of hypothyroidism in the United States (see foramen cecumof the tongue (locatedin the midline subsequent discussion). Worldwide, iodine defi- at the circumvallate papillae level) to the normal ciency (endemic goiter) is another cause of hypothy- position of the thyroid gland is persistent.Although roidism but is infrequently seen in developed coun- a congenital lesion, 50% of casespresent after age 10 years.Any epithelial-lined tract has the potential for obstruction and a cyst may occur due to retained secretions.In thyroglossalduct cyst,a midline cystic massis observed,which is located in an infrahyoid level in 65V",hyoid level in 1,5%,and suprahyoid level in 20Voof cases.3It mav occur in a paramedian position in 25Voof cases,usually in the infrahyoid compartment.The stereotypicallocations of the thy- roglossalduct cyst are embedded in the strap mus- clesbelow the hyoid bone, or at the midline junction of the hyoid bone abovethe strap muscle insertions (Fig. 23). Becausethe fluid in the thyroglossal duct cyst may have a high protein content, it may appear cystic with some internal echoeson ultrasonogra- phy. It moves with swallowing or sticking the tongue out. On CT, the noninfected thyroglossal duct cyst varies in intensity from markedly hypo- dense (with no protein content) to slightly hyper- dense (with high protein or hemorrhage within). On MR scans,the thyroglossal duct cyst may be either dark or bright on Tl-weighted scansbut is typically hyperintense on T2-weighted scans.En- Figure 22. Graves'disease on nuclearscintigraphy. This hancementis uncommon in thyroglossal duct cysts glandwas enlargedand showedincreased radiotracer up- unless the lesion has been traumatized or infected. take. Note the pyramidallobe (arrows),which is also en- In those instances, peripheral rim enhancement larged. may occur. 454 YOUSEM

Figure 23. A and B, Thyroglossalduct cyst.A, A cyst embeddedin the strap musclecan be seen on thisT2-weighted MR scan"Note the tract(arrows) extending from the midlineto the rightlateral position in thisparamedian thyroglossal ductal cyst. B, A differentpatient had a hyperintensemidline thyroglossal ductalcyst (arrows)on this T1-weightedscan.

Ectopic thyroid tissue is found in approximately medicine study to determine whether a lingual mass 25Voto 33% of thyroglossal duct cysts.3'27The inci- represents thyroid tissue, and also to search for dence of carcinoma within the thyroid tissue of a other (ectopic or normally located) thyroid tissue, is 'l.Vo.3'27 thyroglossal duct cyst is less than Y,lhen 1t favored over cross-sectional imaging. The thyroidal occurs, it is usually papillary carcinoma. tissue within the tongue can be identified by its high Recurrence rates of approximately 4% are ob- attenuation on CT (due to iodine accumulation) or served after attempted removal of thyroglossal duct its avid contrast enhancement. In a similar fashion, cysts.26The surgery removes the entire tract of the the MR scan demonstrates bright tissue that avidly duct including the middle one fourth of the hyoid enhances in the middle of the tongue. bone and a portion of the base of the tongue that A malignancy arising within a lingual thyroid includes the foramen cecum (Sistrunk procedure).23 gland is more common than one in a thyroglossal Rarely, the tract of the thyroglossil duct may duct cyst. At least one report noted an incidence serve as conduit for infection to the thyroid gland of 2.8%.aB leading to acute suppurative thyroiditis.3'? Aberrant Thyroid Tissue LingualThyroid Glands Thyroid tissue lateral to the jugular vein unassoci- Lingual thyroid tissue occurs in 1 in 3000 patients ated with lymphadenopathy may occur due to who have thyroid disease and represents the most anomalous development and is termed lateral aber- common form of functioning ectopic thyroid tis- rant thyroid tissue. This phrase is rarely used noq sue.66Itis also the most common benign mass found because most casesof lateral aberrant thyroid tissue at the circumvallate papillae. The lingual thyroid actually represented thyroid carcinoma metastases gland represents arrest of migration of the thyroid to lymph nodes. Nonetheless, in rare instances, thy- tissue within the tongue, usually in the midline be- roid tissue may be "seeded" to this location by tween the circumvallate papillae and the epiglottis. trauma, surgery, thyroiditis, or goiters, and must be This may be a complete arrest or incomplete arrest distinguished from metastatic thyroid carcinoma. of migration. Lingual thyroid glands are associated Undescended thyroid tissue sometimes may be with absence of thyroid tissue in the neck in 70% seen in the anterior neck superficial to the hyoid lo 80Voof cases and are seen much more commonly bone. Aberrant thyroid tissue also may be found in in women.6'23'66Patients often present in puberty, the trachea. In this site, women are affected more when the tissue may expand rapidly. Variation in commonly than men, and the thyroid tissue may size with menstruation also has been reported. resPond to hormonal influences. The primary role of imaging is to identify whether Substernal thyroid tissue is not uncommon but normal thyroidal tissue is present in the lower neck usually occurs in association with a goitrous gland so that complete excision or transplantation of the extending downward rather than as isolated tissue. lingual thyroid tissue may be contemplated. If no Tracheal or esophageal compression on a chest ra- other thyroid tissue is present, the patient is con- diograph may be the presenting finding. Imaging to signed to lifelong thyroid replacement therapy if the distinguish a goiter from mediastinal adenopathy, lingual thyroid gland is totally removed. A nuclear thymoma, Iymphoma, , carcinoma, or an PARATHYROID AND THYROID IMAGING 455 unusual bronchogenic cyst is usually pursued thyroiditis but has the most fulminant clinical pre- with CT. sentation. Struma ovarii, the presenceof functioning thy- roid tissue in the ovaries or in an ovarian teratoma Hashimoto's Thyroiditis or dermoid, is rare. Most other forms of thyroiditis are subacute or chronic diseases. Hashimoto's (chronic lymphocytic Inflammatory Lesions thyroiditis) is the most common of the chronic thy- roiditides, being five to ten times more frequent No specificscintigraphic, sonographic, CT, or MR than subacute thyroiditis.s8 It is the most common appearancesdifferentiate among the various in- thyroiditis in children. The diagnosis is based on flammatory processesinvolving the thyroid gland. serology because the disease is an autoimmune pro- The most useful imaging study is the nuclear medi- cess with antigenic stimulation to thyroglobulin, cine scan, performed with ee'Tc pertechnetateor colloid, and other thyroid cell antigens. Serum levels radioactive iodins (tzal or 131I),which determines of antimicrosomal antibodies are elevated and the activity of the thyroid gland. The value of the FNAs may reveal a preponderance of lymphocytes, imaging studies, however, pales in comparision centroblasts, and Hurthle's cells.el Women are af- with that of serology for distinguishing various in- fected nearly 20 times more frequently than men, flammatory lesions of the thyroid gland. On the and the chief complaint is usually enlargement and other hand, if imaging is to be used as a map for tenderness of the thyroid gland. Hypothyroidism surgical correctionor resectionof the thyroid gland, is present at presentation or develops later in 50% MR imaging and ultrasonography seem to be of of cases. particular benefit. In some instances,the adminis- The gland with Hashimoto's thyroiditis is en- tration of iodine on an enhanced CT scan might larged and shows multinodularity and heteroge- precipitate thyroid storm (acuteoutpouring of thy- neous increased or decreased uptake of radiotrac- roid hormone), so CT usually is avoided. ers. Although early in the disease there may be increased uptake of iodine on nuclear medicine Suppurative Thyroiditis studies, the usual response is diminished or normal thyroid uptake on imaging.el Patients who trap Acute suppurative thyroiditis presentswith acute more tracer have a greater chance of returning to a onset of pain and swelling in the thyroid gland euthyroid state than those who do not. Although associatedwith fever, odynophagia, and dyspha- Hashimoto's thyroiditis shows no greater risk for gia.25The role of imaging is to exclude a pyriform carcinoma, it seems to predispose to non-Hodgkin's sinus or thyroglossal duct fistula as an etiology for lymphoma.sl Hashimoto's thyroiditis in the pres- the acutesuppurative thyroiditis. This entity occurs ence of thyroid lymphoma is seen In 25% to 67Vo sometimes in associationwith a fourth branchial of cases.e'81 cleft anomaly and has a left-sided predominance.2s On ultrasonography, the thyroid gland is sym- Imaging may identify leakage from the pyriform metrically enlarged and hypoechoic but may have sinus to the lateral neck at the thyroid gland level. nodules within it (Fig. 24). Calcification is seen in Acute suppurative thyroiditis is the rarest form of the chronic stages. On T2-weighted scans, MR im-

Figure 24. A and B, Hashimoto'sthyroiditis on ultrasonography.4, Sagittalscan through the rightlobe shows an enlargedgland with some nodularity(arrows) to it. B, The transverseview also depictsa prominentirregular gland. 456 YOUSEM

Figure 25. A and B, Riedel'sthyroiditis. ,4, This thyroid"mass" has infiltratedthe subglottis,causing thickeningof the mucosa.Obliteration of thefat planesbetween thyroid gland and rightside of esophagus also is present.B, AI a more inferiorlevel, one can see the diffuseinfiltrative nature of the lesioninto the trachealrinos.

aging has shown increased signal intensity, some- cated.3ePain, fever, and fatigue are common pres- times with linear low intensity bands thought to enting symptoms.Subacute thyroiditis may present represent fibrosis.18,57 (50% of cases)with acute toxic hyperthyroidism Hashimoto's disease has been associated with with subsequentreturn to a euthyroid state after other autoimmune entities, such as pernicious ane- 1 to 2 months.66Hypothyroidism occurs approxi- mia, Sjogren's syndrome, lupus, rheumatoid arthri- mately 2 to 4 months after onset and, typically by tis, Addison's disease, and Graves' disease. 6 months after the acute onset, the patient reverts to euthyroidism.s8Patients are treatedmedically be- Riedel's Thyroiditis cause the prognosis is good for return of normal thyroid function. Subacutethyroiditis is hypoechoic Reidel's thyroiditis (struma thyroiditis) is an un- on ultrasonography,although there may be atrophy common chronic inflammatorv lesion of the thvroid of thyroidal tissue with time.20Nuclear medicine gland and neck. The disease may be bilateial or studies show heterogeneousuptake that varies ac- unilateral and is more common in women than in cording to the stage of the disease. men. Patients present with evidence of mass effect with compression of the trachea, hoarseness, and difficulty ln swallowing. The patients are usually Miscellaneous hypothyroid. On imaging, Riedel thyroiditis is ho- External beam radiation may causea chronic thy- mogeneously hypoechoic on ultrasound and is usu- roiditis associatedwith fibrosis. In low doses(used ally hypodense to normal thyroid tissue on CT.20.s7 in years past for radiating the thymus, adenoids, The lesion may be isodense to muscle on unen- acne/or ringworm), radiation predisposesto papil- hanced CT. Riedel thyroiditis may spread to outside lary carcinoma. Radioactive iodine treatment of the thyroid gland, infiltrating and obliterating also causessevere fibrosis and atrophy of the gland. adjacent tissue planes (Fig. 25). The characteristic Amyloidosis and hemochromatosis may affect finding on MR images is hypointensity on T1- and the thyroid gland and lead to decreasedsignal inten- T2-weighted sequences with infiltration of adjacent sity on T2-weighted MR scans. structures of the neck.sTThe low intensity on MR Tuberculosis, sarcoidosis,and fungal infections images is believed to be caused by the fibrotic nature may cause a granulomatous inflammation of the of the disorder. This lesion may be associated with thyroid gland but are uncommon conditions.2 retroperitoneal fibrosis, mediastinal fibrosis, scle- rosing cholangitis, and orbital pseudotumor. It is distinguished from Hashimoto's thyroiditis, which is typically increased in intensity on T2-weighted References MR images. 1. AuffermannW, ClarkOH, Thurnher S, et al: Recurrent de Queruain'sThyroiditis thyroid carcinoma: Characteristics on MR images. Ra- -7 de thyroiditis (subacute diology'1. 68:753 57, 1.988 Quervain's thyroiditis) 2. Basso LV, Keeling C, Goris ML: Parathyroid imaging. is a disease of middle age occurring most commonly Use of dual isotope scintigraphy for the localization in women after an upper respiratory infection. Cox- of adenomas before surgery. Clin Nucl Med 17:380- sackie, ECHO, and mumps viruses have been impli- 383,1.992 PARATHYROID AND THYROID IMAGING 457

3. BatsakisJG: Tumors of the Head and Neck. Clinical 22. Gorman B, CharboneauJW, JamesEM, et al: Medul- and Pathological Considerations. Baltimore, Wil- lary thyroid carcinoma: Role of high-resolution US. liams & Wilktns, "1979. Radiology 762:'1 47 -1,50, 7987 4. BeahrsOH, Kiernan PD, Hubert JP Jr: Cancer of the 23. Guneri A, Ceryan K, Igci E. et al: Lingual thyroid: thyroid gland. In Suen JY, Myers E (eds): Cancer of The diagnostic value of magnetic resonanceimaging. the Head and Neck. New York, Churchill Livingstone, J Laryngol Otol 105:493-495,7997 1981,pp 599-632 24. Hamilton R"Greenburg BM, GefterW, et al: Successful 5. Brown LR" Aughenbaugh LG: Massesof the anterior localizationof parathyroid adenomasby magneticres- mediastinum: CT and MR imaging. AJR Am J Roent- onanceimaging. Am I Surg 155:370-373,7988 genol L57:1.77 7-7780, 7997 25. Hatabu H, KasagiK, YamamotoK, et al: Acute suppu- 6. Burman KD, AndersonJH, Wartofsky L, et al: Manage- rative thyroiditis associatedwith pyriform sinus fis- ment of patients with thyroid carcinoma:Application tula: Sonographic findings. AJR Am J Roentgenol of thallium-20l scintigraphy and magnetic resonance 755:845-847,1990 imaging. I Nucl Med 31:1958-1964,7990 26. Hawkins DB, JacobsenBE, Klatt EC:Cysts of the thp'o- 7. Carlson GL, Farndon JR, Clayton B, et al: Thallium glossal duct. Laryngoscope92:7254-7258, L982 isotope scintigraphy and ultrasonography:Compara- 27. Hays LL, Marlow SF Jr: Papillary carcinoma arising tive studies of localization techniquesin primary hy- in a thyroglossal duct cyst. Laryngoscope 78:2L89- perparathyroidism. Br J Stulrg77:327-329,7990 2793,1968 8. CasasAT, Burke Gj, MansbergerAR jr, et al: Impact 28. Health H, Hodgson SF,Kennedy MA: Primary hyper- of technetium-99m-sestamibilocalization on operative parathyroidism, incidence, morbidity, and potential time and successof operationsfor primary hyperpara- impact in a community. N Engl J Med 302:189-193, thyroidism. Am Surg 60:72-76,7994 1980 29. Hindie E, Melliere D, Simon D, Primary hyper- 9. Compagno J, Oertel fE: Malignant lymphoma and et aI: other lymphoproliferative disorders of the thyroid parathyroidism: Is technetium 99m-sestamibi/iodine- 123subtraction scanningthe best procedure to locate gland: Clinicopathologic study of 245cases. Am J Clin Pathol74:1-11,1980 enlarged glands before surgery? J Clin Endocrinol Metab 80:302-307,1,995 10. CompagnoJ: Diseasesof the thyroid. In BarnesL (ed): Surgical Pathology of the Head and Neck. New York, 30. Intenzo CM, Park CH, Kim SM: Thyroid scintigraphy Marcel Dekker, 1,985,pp 7435-1486 of hyperthyroxinemia [review]. Clin Nucl Med 1.8:987-985,7993 11. Dorr U, Wurstlin S, Frank-RaueK, et al: Somatostatin 31. Kang YS, Rosen K, Clark OH, et al: Localization receptor scintigraphy and magnetic resonance im- of abnormalparathyroid glands of the mediastinum with aging in recurrent medullary thyroid carcinoma: A MR imaging. Radiology 789:737-747, 7993 comparative study. Horm Metab Res Suppl 27:48- 32. Kawanaka M, Sugimoto Y, Suehiro M, et al: Thyroid 55, 1,993 imaging in a typical caseof acutesuppurative thyroidi- 12. Edis AJ,Sheedy PF, Beahrs OH, et al: Resultsof reoper- tis with abscessformation due to infection from a ation for hyperparathyroidism,with evaluationof pre- persistent thyroglossal duct. Ann Nucl Med 8:159- operative localization studies. Surgery 84:384-397, 762,7994 7978 33. Khan A, Samtani S, Varma VM, et al: Preoperative 13. EdmonsonG& Charboneau EM, et aI: JW,James Para- parathyroid localization: Prospective evaluition of thyroid carcinoma:High-frequency sonographic fea- technetium 99m sestamibi. Otolaryngol Head Neck tures. Radiology 767:65-67,7986 Surg 1.71:467 - 472,1,99 4 14. el-Desouki M: T1-201thyroid imaging in differentiat- 34. Kitapci MT, TastekinG, Turgut M, et ai: Preoperatrve ing benign from malignant thyroid nodules.Clin Nucl localization of parathyroid carcinoma using Tc-99m Med'16:425-430,1991 MIBI. Clin Nucl Med 78:277-279,7993 15. FoldesI, Levay A,Stotz G: Comparativescanning of 35. Klieger PS,Wilson GA, GreenspanBS: The usefulness thyroid nodules with technetium-99m pertechnetate of the dynamic phasein pertechnetatethyroid imaging and technetium-99m methoxyisobutylisonitrile. Eur for solitary hypofunctioning nodules. Clin Nucl Med J Nucl Med 20:330-333,7993 17:617-622,1992 16. Freitas Freitas AE: Thyroid JE, and parathyroid im- 36. Kneeland JB,Kruback AJ, Lawson TL, et al: Enlarged aging [review]. Semin Nucl Med 24:234-245,7994 parathyroid glands:High-resolution local coil MR im- 17. Funari M, Campos Z, Gooding GA, et al: MRI and aging. Radiology 162:143-746,1987 ultrasound detection of asymptomatic thyroid nod- 37. Lebouthillier G, Morais f, Picard M, et al: Tc-99mses- ules in hyperparathyroidism. Journal of Computed tamibi and other agentsin the detection of metastatic Axial Tomography 76:675-679,1992 medullary carcinoma of the thyroid. Clin Nucl Med 18. Gefter WB, Spritzer CE, LiVolsi VA, et al: Thyroid 18:657-661,1993 imaging with high-field strength surface-coilMR. Ra- 38. Levin KE, Clark AH, Duh QY, et al: Reoperativethy- diology 764:483- 490, 1987 roid surgery. Surgery 171:604-609,1992 19. Gharib H, Goellner JR"Johnson DA: FNA cytology of 39. Livolsi V: The thyroid and parathyroid.Iz SternbergSS the thyroid: A 12year experiencewith 11,000biopsies. (ed): Diagnostic Surgical Pathology, ed 2. New York, Clin Lab Med 13:699-71,0,1995 Raven Press,7994, pp 523-560 20. Gooding GA: Sonography of the thyroid and par athy- 40. Livolsi VA: Pathology of the parathyroid glands. 1z roid. Radiol Clin North Am 37:967-989,7993 Barnes L (ed): Surgical Pathology of the Head and 21. Gooding GAW, Okerlund MD, Stark DD, et al: Para- Neck. Marcel Dekker, New York, 1985,pp 1487-7563 th1'roid imaging: Comparison of double-tracer 41. Majors JD, Burke GJ,Mansberger AR Jr, et al: Techne- (Tl-201,Tc-99m) scintigraphy and high-resolution ul- tium Tc-99m sestamibi scan for localizing abnormal trasound. Radiology 161,:57-64,1,986 parathyroid glands after previous neck operations: 458 YoUSEM

Preliminary experience in reoperative cases. South 63. Russell CF, Laird JD, Ferguson WR: Scan-directed uni- Med J 88:327-330, l9c5 lateral cervical exploration for parathyroid adenoma: 42. Mancuso AA, Dillon WP: The neck. Radiol Ciin North A legitimate approach? World J Surg 74:406-409, 1,990 Am 27:407-434, 7989 64. Sandler MP, Patton JA, Ossoff RH: Recent advances 43. Mattar AG, Wright ES, Chittal SM, et al: Impact on in thyroid imaging. Otolaryngol Clin North Am surgery of preoperative localization of parathyroid le- 23:257-270,1990 sions with dual radionuclide subtraction scanning. 65. Satava RM, Beahrs OH, Scholz DA: Success rate of Can Surg 29:57-59,7986 J cervical exploration for hyperparathyroidism. Arch 44. Miller DL, Doppman JL, Krudy AG, et al: Localization Surg 110:625-627,1975 of parathyroid adenomas in patients who have under- 66. Schwartz SI, Shires GT, Spencer FC, et al: Principles gone surgery. Part IL lnvasive procedures. Radiology of Surgery, ed 3. New Yorl McGraw Hill, 7979, p 7547 762:138-747, 1987 67. Seelos KC, DeMarco R, Clark OH, et al: Persistent 45. Miller DL, Doppman Shawker TH, et al: Localiza- JL, and recurrent hyperparathyroidism: Assessment with tion of parathyroid adenomas in patients who have gadopentetate dimeglumine-enhanced MR imaging. undergone surgery. Part L Noninvasive imaging Radiology 177:373-378, 1990 methods. Radiology 162:133-737, 7987 68. Shamma FN, Abrahams Jj: Imaging in endocrine dis- 46. Miller DL: Pre-operative localization and international orders. J Reprod Med 37:39-45, 1992 treatment of parathyroid tumors: When and how? 69. Shibata T, Noma S, Nakano Y, et al: Primary thyroid World J 9:rg 75:706-775, 7997 lymphoma: MR appearance. Comput Assist Tomogr 47. Mitchell BK, Kinder BI(, Cornelius E, et aI: Primary J 15:629-633,7997 hyperparathyroidism: Preoperative localization using 70. Shulkin BL, Shapiro B: The role of imaging tests in technetium-sestamibi scanning. J Clin Endocrinol Met- abol 80:7-70,1995 the diagnosis of thyroid carcinoma. Endocrinol Metab 48. Montgomery ML: Lingual thyroid: Comprehensive re- Clin North Am 79:523-543, 1990 71. Solbiati L, A, De view. West J St:ng 43:66L-677, 1.935 Giangrande Pra L, et aI: Percutaneous 49. Morita ET, Kwan WP, Clark OH: Technetium Tc-99m ethanol inlection of parathyroid tumors and ultra- sestamibi for parathyroid imaging. West Med sound guidance: Treatment for secondary hyperpara- 761,:41,3,1994 thyroidism. Radiology 755:607-670, 7985 72. 50. Neumann DR, Esselstyn CB, Eastwood J, et al: Local- Solbiati L, Volterrani L,Rizzatto G, et aI: The thyroid ization of mediastinal parathyroid adenoma in recur- gland with low uptake lesions: Evaluation by ultra- rent postoperative hyperparathyroidism with Tc-99m sound. Radiology 755:187-197, 1985 sestamibi SPECT. Clin Nucl Med 20:775, 1.995 73. Som PM, Brandwein M, Lidov M, et al: The varied 51. Nishimura K: Imaging of the thyroid and parathyroid. appearance of papillary carcinoma cervical nodal dis- Curr Opin Radiol 4:136-1 40, 1992 ease: CT and MR findings. AINR Am J Neuroradiol 52. Noma S, Kanaoka M, Minami S, et al: Thvroid masses: 75:71.29-11.38, 7994 MR imaging and patholgic correlation. Radiology 74. Som PM: Lymph nodes of the neck. Radiology 768:759*764, 1988 165:593-600, 7987 53. O'Doherty MJ, Kettle AG, Wells P, et al: Parathyroid 75. Sommer B, Welter HF, Spelsberg R et al: Computed imaging with technetium-99m-sestamibi: Preopera- tomography for localizing enlarged parathyroid tive localization and tissue uptake studies. J Nucl Med glands in primary hyperparathyroidism. ]ournal of 33:373-378, 1,992 Computer Assisted Tomography 6:521-526, 1982 54. Oates E: Improved parathyroid scintigraphy with Tc- 76. Spritzer CE, Gefter WB, Hamilton R" et al: Abnormal 99rn a MIBI, superior radiotracer. Appl Radiol 37- paratyroid glands: High resolution MR imaging. Radi- 42,7994 ology 162-487 -491, 1987 55. Ohnishi T, Noguchi S, Murakami N, et aI: MR imaging 77. Stark DD, Cooding GAW, Moss AA: Parathyroid im- in patients with primary thyroid lymphoma. AJNR aging: Comparison of high-resolution CT and high- Am J Neuroradiol 13:1196-1198,7992 resolution sonography. AJR Am J Roentgenol 141:633- 56. Peck WW, Higgins CB, Fisher MR, et al: Hyperpara- 638,1983 thyroidism: Comparison of MR imaging with radionu- 78. Sutton RT, Reading CC, Charboneau et aI: US- clide scanning. Radiology 1 63:41.5-420, 1.987 JW, guided biopsy of neck masses in postoperative man- 57. Perez Fontan FJ, Cordido Carballido F, Pombo agement of patients with thyroid cancer. Radiology Felipe F, et al: Riedel thyroiditis: US, CT, and MR 168:769-772, 1988 evaluation. J Comput Assist Tomogr 77:324-325,1993 79. Szybinski Z, Huszno B, Golkowski F, 58. Price DC: Radioisotopic evaluation of the thyroid and et al: Technetium the parathyroids. Radiol Clin North Am 31:991- 99m-methoxyisobutylisonitrile in early diagnosis of 7075, 1,993 thyroid cancer. Endokrynologia Polska 44:427-433, 7993 59. Reading CC, Charboneau JW, James EM, et al: High- 80. Taillefer R, Boucher Y, Potvin C, resolution parathyroid sonography. AIR Am J Roent- et al: Detection and genol 139:539-546, 7982 localization of parathyroid adenomas in patients with 60. Reading CC, Gorman CA: Thyroid imaging tech- hyperparathyroidism using a single radionuclide im- '13:777-724, niques. Clin Lab Med 1993 aging procedure with technetium-99m-sestamibi 61. Rodriquez JM, Tezelman S, Siperstein AE, et al: Local- (double phase study). J Nucl Med 33:7801-7807, 7992 ization procedures in patients with persistent or recur- 81. Takashima S, Ikezoe J, Morimoto S, et al: Primary rent hyperparathyroidism. Arch Surg. 1.29:870-875, thyroid lymphoma: Evaluation with CT. Radiology 1.994 768:765-768, 1988 62. Roe SM, Burns RP, Graham LD et al: Cost-effectiveness 82. Takashima S, Morimoto S, Ikezoe J, et al: CT evalua- of preoperative localization studies in primary hyper- tion of anaplastic thyroid carcinoma. AJR Am J Roent- . Ann Surg 219:582-586, 1994 genol 754:7079 -1.985, 7990 PARATHYROID AND THYROID IMAGING 459

83.TakashimaS, Nomura N, TanakaH, et al: Congenital 91. Wang PW, Chen HY, Li CH, et al: Tc-99m pertechne- hypothyroidism: Assessmentwith ultrasound. AJNR tatetrapping and thyroid function in Hashimoto'sthy- Am J Neuroradiol 16:"11,1,7-1,'123, 7995 roiditis. Clin Nucl Med 79:777-780,1994 84. Thompson CT: Localization studies in patients with 92. Weber CJ, Vansant J, Alazraki N, et al: Value of hyperparathyroidism. Br J Surg 75:97-98,7988 technetium 99m sestamibi iodine 123 imaging in 85. Thompson NW, EckhauserFE, HarnessJK: The anat- reoperative parathyroid surgery. Surgery 174:1,077- omy of primary hyperparathyroidism. Surgery 92:81.4- 7078, 1993 821.,1.982 93. Wei fP, Burke GJ, Mansberger AR Jr: Preoperative Tibblin S,Bondeson AG, LjungbergO: Unilateral para- imaging of abnormal parathyroid glands in patients thyroidectomy in hyperparathyroidism due to single with hyperparathyroid disease using combination adenoma.Ann Surg 795:245-252,1,982 Tc-99m-pertechnetateand Tc-99m-sestamibiradionu- 87. Uden P, Aspelin P, Berglund f, et al: Preoperative clide scans.Ann Surg 279:568-572,7994 localization in unilateral parathyroid surgery. A cost- 94. Woolner LB, BeahsOH, Black BM, et al: Classification benefit study on ultrasound, computed tomography and prognosis of thy'roid cancer.Am J Surg 102:354- and scintigraphy. Acta Chir Scand 1,50:29-35,1,990 387,1961. 88. van Heerden|A, Weiland LH, ReMineWH, et al: Can- 95. Yao M, JamiesonC, Blend R: Magnetic resonanceim- cer of the . Arch *rg 774:475- aging in preoperativelocalization of diseasedparathy- 479,1.979 roid glands: A comparisonwith isotopescanning and 89 VergesB, CercueilJP, Pfitzenmyer P, et al: Percutane- ultrasonography. Can J Swg 36:241-244,1993 ous ethanol injection of parathyroid adenomasin pri- 96. Yen TC, Lin HD, Lee CH, et al: The role of technetium- mary hyperparathyroidism. Lancet 337:7421,-7422, 99m sestamibiwhole-body scansin diagnosing meta- 1,997 staticHurthle cell carcinomaof the thyroid gland after 90.Walker JM, Margouleff D: A Clinical Manual of Nu- total thvroidectomv: A comparison with iodine-131 clear Medicine. Norwalk, CT, Appleton-Century- and thailium-2Of #note-Uoay scans.Eur J Nucl Med Crofts, 1984 27:980-983,7994

Addressreprint requeststo David M. Yousem, MD Department of Radiology University of PennsylvaniaMedical Center 3400Spruce Street Philadelphia, PA 19104