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

PARATHYROID IMAGING

Imaging of the parathyroid glands revolvesaround the detection of parathvroid adenomas andhyperplastic parathyroid glands in the setting oIprimary hyperparathyroidism. Arguments for andagainst imaging and which imaging modality touse have been hotly debated in the radiologic andsurgical literature.

Anatomy and lmaging

The parathyroid glands are derived from the third(lower parathyroid glands) and fourth (upper para-thyroid glands) pharyngeal pouches. Whereas themajority of people have four glands (a pair at theupper and lower poles of the thyroid gland),25%of individuals have more than this number.3e,a0 Al-though the parathyroid glands may be aberrantlylocated anywhere from the carotid bifurcation to theanterior mediastinum, inferior migration of thoseglands derived from the third pharyngeal pouchoccurs most frequently.3t Of the two dominant celltypes in the parathyroid glands, the chief cells andthe oxyphil cells, the former are the predominantsource of parathormone.

Vascular supply to the parathyroid glands is usu-ally through the superior and inferior thyroidal ar-teries, with drainage to thyroidal veins. The glandsare innervated through the cervical sympatheticplexus.

There are several options for imaging the parathy-roid glands; these include ultrasonography, com-puted tomography (CT), magnetic resonance (MR)

PARATHYROID ANDTHYROID IMAGING

David M. Yousem. MD

imaging, angiography, and nuclear medicine scin-tigraphy. The advantages and disadvantages o{each of the imaging modalities described are sum-marized in Table 1.

High frequency (5-10 MHz) ultrasonography isthe least invasive of the imaging modalities usedto search for parathyroid adenomas because it doesnot require intravenous injections of any com-pounds. Unfortunatelp its accuracy is less than thatof the other modalities mainly because of the diffi-culty in identifying ectopic parathyroid adenomasthat may occur throughout the neck, behind air-filled strucfures, or in the anterior mediastinumwhere acoustic impedance by bone or air preventsadequate imaging. Nonetheless, for parathyroid ad-enomas that are located in a perithvroidal location.ultrasonography is an excel lent imaging choice.

CT offers the benefit of cross-sectional imagingfor parathyroid adenoma localization. Because theentire neck from skull base to anterior mediastinumcan be scanned with CT, the possibility of detectingectopic parathyroid adenomas is increased. Distin-guishing lymphadenopathy from parathyroid ade-nomas is a problem encountered with CT (as well aswith ultrasonography and MR imaging). The otherdisadvantage of CT is that it requires the adminis-tration of iodinated intravenous contrast agents.These contrast agents are essential for distinguish-ing blood vessels from adenomas or lymphadenop-athy. Moreover, the use of iodinated contrast agentsprevents subsequent imaging with iodine-based nu-clear medicine agents because of the uptake of con-trast by the thyroid gland. It is necessary to wait atleast 6 weeks after contrast-enhanced CT scans toimage the thyroid gland with iodinated nuclear

From the Departments of Radiology and Otorhinolaryngology-Head and Neck Surgery, The University of PennsylvaniaMedical Center, Philadelphia, Pennsylvania

NEUROIMAGING CLINICS OF NORTH AMERICA

VOLUME 6 . NUMBER 2. i|'{AY '].996 435

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Table 1. ADVANTAGES AND DISADVANTAGES OF VARIOUS IMAGING MODALITIES FOR DETECTION OFPARATHYROID ADENOMAS

Examination Advantages Disadvantages

CT Examines head. neck. and chestEasy detection of calcificationBiopsy capable

Examines head. neck. and chestNo iodinated conlrast reouiredExcellent soft tissue discrimination

Examines head and neck wellFunctional, not anatomic imagingDistinguishes nodes from adenomasReasonable costExamines neck welllnexoensiveNoninvasiveReal-time, biopsy capable

Requires iodinated contrastlodinated contrast affects thyroid imaging by scintigraphyShoulder artifactsDifficult to differentiate node versus adenomaExoensiveDifficult to differentiate node versus adenomaIntravenous gadolinium agent employedRequires patient cooperation, no claustrophobiaVery expensiveLower yield for ectopic glands especially in chestIntrathyroidal masses indistinguishable from adenomasSmaller lesions easily missed

Examines head and chest poorlyCannot differentiate nodes and adenomas

MR imaging

Nuclear medicinescintigraphy

Ultrasonography

medicine agents. Contrast enhancement is not thesolution to parathyroid imaging; only 25% of para-thyroid adenomas demonstrate noticeable enhance-ment.z False-negative studies with CT also may oc-cur in the setting of poor-quality images fromshoulder artifacts.

MR imaging with gadolinium enhancement is an-other useful study for evaluating patients with hy-perparathyroidism. On T2-weighted scans andpost-gadolinium T1-weighted scans, parathyroidadenomas are bright against a dark, fat-suppressedbackground.3l'36'56'67'76 MR imaging is limited by thedistribution and coverage of the surface coil usedto detect parathyroid adenomas and also by anymotion artifact that may occur during imaging.Nonetheless, with the appropriate surface coil andinstructions to the patient, MR imaging is able toadeouatelv evaluate the entire neck and anteriormediastinum. As with the other modalities listed,the potential for misdiagnosing lymphadenopathyas parathyroid adenomas also exists with MR im-aging.

The choices for scintigraphic localization of para-thgoid adenomas include thallium (Tl)-201-tech-netium (Tc)-99m pertechnetate subtraction scanning,ee-Tc-sestamibi (hexakis-2-methoxy-isobutyl-isonitrile) subtraction imaging with iodine-123(I-123) or ehTc pertechnetate, and ee^Tc-sestamibi

imaging without subtraction. The subtractiontechnioues allow tracers that are concentrated inthe thyroid gland (pertechnetate and iodine) to besubtracted from those (thallium and sestamibi) thataccumulate in both thyroid glands and parathyroidadenomas. Thallium is a potassium analogue thatmay concentrate in parathyroid adenomas becauseof changes in potassium turnover in active cells.The mechanism for sestamibi uptake is poorly un-derstood but may relate to mitochondrial densityin oxyphil cells, blood flow within adenomas, or

potassium turnover.ae'sa Because sestamibi uptake inparathyroid adenomas persists after thyroid glandwashout, it can be used without subtraction tech-niques if one performs delayed images. The difficulttask of patient immobilization and accurate su-perimposition of subtracted images, required bythallium-pertechnetate studies, is obviated with de-layed sestamibi imaging.

Of the parathyroid agents, thallium emits low-energy, low-penetrating 80 keV photons andwashes out of parathyroid adenomas relatively rap-idly. ee'Tc-sestamibi has 140 keV photons that pene-trate the anterior neck and mediastinal soft tissuesbetter and is concentrated at a higher rate and fora longer time within an adenoma than thallium.ee*Tc-sestamibi, therefore, produces higher signal-to-noise images than thallium subtraction scans.saSingle-photon emission computed tomography(SPECT) scanning also can be combined with high-dose ee'Tc sestamibi scintigraphy for more accurateparathyroid adenoma localization.ae

Hyperparathyroidism

Hyperparathyroidism has an incidence of 0.0377oin the United States.28 Patients mav present withthe classic findings of stones (renal laiculi), groans(abdominal pain), bones (demineralization or ar-thritis), or moans (psychiatric disturbances). Pri-mary hyperparathyroidism is caused by a solitaryparathvroid adenoma in 80% to 85% of cases.20'21'6a.s+,ss iltp"rplastic parathyroid glands (12-15%),multiple adenomas (2-3E"), and parathyroid carci-noma (<2%) account for the remaining 15Vo to20Va.20, 21' 58, u,85 Parathyroid adenomas may be ectopic(not around the thyroid bed) in 1,0% to 20Vo ofcases.16, 21, 50, 58

Parathyroid imaging is controversial not onlyfrom the standpoint of the indications for imagingbut also from the issue of which modality (if any)to choose. In most institutions, preoperative local-ization of the parathyroid glands by imaging is notperformed before the first surgery (for previouslyoperated patients, see subsequent discussion). Thisstems from the early surgical literature that suggeststhat operative time, morbidity, and mortality is notsignificantly influenced by preoperative localizationof parathyroid adenomas for hyperparathyroid-ism.7' a6,62 The surgical exploration entails bilateraldissection of the perithyroidal region, emphasizingthe inferior poles, where most parathyroid adeno-mas occur. In experienced hands, this surgical pro-cedure can be performed quickly and accuratelywith success rates of over 90Vo.12'5e,62,65,84 This hasled Doppman84 to state that the best localizationprocedure a patient can obtain for parathyroid ade-nomas is to locate "an experienced parathyroidsurgeon."

Proponents of preoperative localization of para-thyroid adenomas even in unoperated cases cite(1) the need for only unilateral dissections when anadenoma is evident on imaging; (2) the identifica-tion of ectopic adenomas preoperatively, allowingbetter planning and patient education; (3) detectionof other head and neck masses that mav reouiretreatment at the same time (e.g., thyroid masies);and (4) the reduction in operating room time, recur-rent laryngeal nerve paralysis, and postoperativehypoparathyroidism when preoperative imaging isperformed.38'43'63'6'86 In two studies bv Russell andtasas and their colleagues, the differ6nce betweenmean operating times with (71 minutes and 135minutes) and without (97 minutes and 180 minutes)preoperative imaging justified the cost of the im-aging test.8'63 The operative success rate also im-proved from 90% to 1,00Vo with preoperative im-aging.8 Uden also noted that the time for surgeryand anesthesia decreased with preoperative im-aging; however, when a cost-benefit analysis wasperformed, he found that the cost of the imagingprocedure outweighed its benefit.8T A reduction of28 minutes of operating room time in the study byRoe and colleagues did not justify the $901 meancost of localization.62 Other surgeons take a centristposition regarding bilateral or unilateral neck ex-plorations. They perform unilateral neck dissectionsif imaging studies are definitive but convert to bilat-eral surgery if (1) imaging is equivocal or showsmultifocal abnormality, (2) more than one enlargedgland is identified at surgery, (3) the patient hasa 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 ina stereotypical perithyroidal location, the surgeonmay empirically explore the anterior mediastinum,deep cervical space, periesophageal grooves, or ca-rotid sheath region. The yield of surgery in this

PARATHYROID AND THYROID IMAGING 437

scenario is much lower (<70% successful) than thatexpected for those adenomas in a perithvroidal loca-tion(>907o success rate), and the surgiial complica-tion rate increases with such blind exoorations.l2The intrathvroidal parathvroid adenomi. which ac-counts for a small'percentage of cases, cannot bereadily distinguished from thyroid adenomas andposes a particularly difficult problem.a5'84 To confusematters further, thyroidal abnormalities occur in asmany as 40% to 48Vo of patients with hyperpara-thyroidism.la 5e. e5 These factors have led less-experienced surgeons and those who have had aIess successful track record to choose preoper-ative localization of parathyroid adenomas.

Parathyroid Adenomas

Exactly how accurate are the imaging studiesfor detecting parathyroid adenomas? On ultraso-nography, parathyroid adenomas appear as oval,oblong, or bulbous lesions with echogenicity lessthan that of the thyroid gland (Fig. t;.s0, u Usinghigh-resolution ultrasound in a study of more than150 patients, a sensitivity of 64Vo and specificityof 94Vo for adenomas and hyperplastic glands wasachieved.5e Of those glands greater than 1 g in size,ultrasonography had a detection rate of 95%.se Otherinvestigators also quote sonographic sensitivities of

Figure 1. Ultrasonogram of parathyroid adenoma. Deepto the thyroid tissue, one can see a hypoechoic mass(arrows) representing a parathyroid adenoma.

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60Va to 707o and specificities in the range of 907a to967a.20,21,36, n

When Stark and colleagues compared the accu-racy of high-resolution CT with ultrasonographyfor detecting parathyroid adenomas, they found thesensitivity of CT to be 70% with a specificity o{90Vo,77 an improvernent over their experience withultrasonography. Sommer and colleagues alsofound CT to be more accurate than ultrasonographyby over 10%; combining the studies yields a detec-tion rate of 89% in patients without previoussurgery.'"

Spritzer and co-workers were among the first toreport on the accuracy of MR imaging (Fig. 2) indetecting parathyroid adenomas.T6 Seventeen pa-tients had adenomas, and MR imaging correctlyidentified 14 of them (82.3Va). Two false-positiveand three false-negative studies for adenomis werereported; given the possibility of 72 glands, thisyields an MR accuracy of 92% for adenomas.

The numerous options for nuclear medicine scan-ning for parathyroid adenomas stem from the factthat there are no agents that are exclusively taken upby the parathyroid glands or adenomas. Therefore,agents that are taken up by parathyroid adenomasand the thyroid glands (thallium and ee^Tc sestam-ibi) must be subtracted from those that are onlytaken up by the thyroid glands (ry*Tc pertechnetateand 123I) (Fig. 3). This then allows visualization ofabnormal uptake by parathyroid adenomas. Com-puter processing is required to enhance accuracywith subtraction techniques.2 At most centers, how-ever, ee^Tc sestamibi imiging is performed withoutsubtraction. Ten to thirtv mCi of ee-Tc sestamibi areinjected with scanning a1 1S-minute intervals for uplo 2 to 4 hours after iniection.aT Because the agentwashes out of the thyroid gland rapidly but iJ re-tained by parathyroid (and thyroid) adenomas, de-Iayed images are all that are usually necessary forgood localization (Fig. 4).

It is not necessary to sacrifice accuracy with thesimpler sestamibi study. The overall sensitivity ofthallium-ee'Tc pertechnetate subtraction scintigra-phy for parathyroid adenoma detection (75-85Vo1z'szis substantially less than that of ee'Tc sestamibi,which runs in the range of 90% to 100%.2e,33,53.54.80No thallium-positive adenomas have been sesta-mibi-negative to date. Furthermore, in a compara-tive study of nonoperated patients, Kneeland andcolleagues found scintigraphy (82Vo) to have highersensitivity rate than MR imaging (74%), CT (74%),and ultrasonography (59%).36 The differences wereonly statistically significant between scintigraphyand ultrasonography.

When Price reviewed the presestamibi literatureup until 1993 Q43 to 1785-cases). he found thatMR imaging had the highest sensitivity rate for thedetection of adenoma (74%) followed by nuclearmedicine studies (72%), CT (65%), and ultrasonog-raphy (63%).58 The false-positive rate of nuclearmedicine (.1.Vo) was lowest compared with MR im-aging (14%), CT (16Vo), and ultrasono graphy (187").Sestamibi data over the past 2 years suggest thatit surpasses all other techniques in sensitivity andaccuracy. Unfortunately, the high rate of thyroidabnormalities (40-487") that coexist with parathy-roid adenomas may lead to false-positive scintigrams because thyroid lesions may concentrate ra-diotracers to the same degree as parathyroidadenomas.as,53,sa Reports of ee*Tc sestamibi uptakein thyroid cancers and their nodal and distant me-tastases signal the possibility for false-positive stud-les.' ' '"

Parathyroid Hype rplasia

Approximately 30% of patients with parathyroidhyperplasia have familial hyperparathyroidism, in-cluding variants of the multiple endocrine neoplasia(MEN) syndromes (Table 2). As noted earlier, hy-

Figure 2. A and B, MR images of parathyroid adenoma. A, A small soft tissue nodule (arror,rr) is seenadjacent to the trachea located below the thyroid gland on the right side. This was a parathyroidadenoma in a low perithyroidal location. A After gadolinium injection, the lesion (arrow'1 enhances avidly.

PARATHYROID AND THYROID IMAGING 439

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

Figure 3. Thallium subtraction study. The thallium scan (top left) can be sequentially subtracted fromthe technetium pertechnetate scan of the thyroid gland (fop right). On the lower set of images, notehow the thyroid gland uptake is eliminated allowing visualization of the inferior pole parathyroid adenomaon the left (arrows\.

Figure 4. A and B, se'Tc sestamibi scan of a parathyroid adenoma. A, Initial technetium-ggm sestamibiscan of the parathyroid region demonstrates uptake in the thyroid gland and parathyroid adenoma(arrows)" B, On delayed imaging, the thyroid uptake has washed out, whereas the parathyroid adenoma(arrow\ has persistent tracer accumulation.

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Table 2. MULTIPLE ENDOCRINE NEOPLASTA (MEN) SyNDROMES

Feature MEN I MEN IIA MEN I IB

EponymParathyroid abnormality

Thyroid lesion

Pituitary lesionsPheochromocytomaOther manifestations

Chromosomal linkage

WermerHyperparathyroidism (90%)

due to hyperplasia morecommonly than adenoma

Goiter, adenomas,thyroiditis are rare

Adenomas (20-30"/.)NoPancreatic islet cell

adenomas ( insul inoma orgastrinoma) 30-35%

Adrenal codex adenomasor carctnomas

Rarely glucagonomas,VlPomas, carcinoid

Zollinger-Ellison syndromeA-D chromosome 11

SippleParathyroid hyperplasia in

20-300/0

Medullary thyroid carcinoma

NoYes

A-D chromosome 10

Mucosal neuroma syndromeVery rare

Medullary thyroid carcinoma

NoYesMucocutaneous neuromasMarfanoid faciesCafe au lait spots

A-D. chromosome 10

perplasia accounts lor 727o to 75% of patients withhyperparathyroidism.

CT is- Leported to have a sensitivity rate of 457oto 88%s'! ultrasonography, 307o to 697o20,21,35,58,n.and MR imaging, 40Vo to 63Va58'76 for detecting hy-perplastic glands. Parathyroid hyperplasia is de-tectedin43% to 657o of cases with thallium subtrac-tion and 55% to 75% with ee-Tc sestamibi.20,21,53, s8' e3

The added accuracy in identifying hyperplasticglands has led to a growing consensus in supportof the use of ee^Tc sestamibi as the optimal agentfor p-alathyroid adenoma and hyperplasia localiza-tion.53,54 80

Parathyroid Carcinoma

Of all patients with hyperparathyroidism, the in-cidence of parathyroid carcinoma (Fig. 5) is only

7% to 2%, although parathyroid carcinoma causeshyperparathyroidism in 85Va to 90Vo of cases.3e,aoMetastases to lymph nodes occur in one third ofcases, and distant metastases in27Vo to287a ofpa-tients. Men and women are affected eouallv.

Edmonson and colleagues noted thai a paratny-roid carcinoma may have the same sonographic ap-pearance as a benign large adenoma (hypoechoicwith or without heterogeneity); only the presenceof local invasion into the thyroid gland, muscles orvessels, or nodal metastases would suggest this di-agnosis.l3

Parathyroid carcinomas have been reported toaccumula te oo'Tc sestamibi.L al

Reoperation for Hyperparathyroidism

During reoperation of previously operated cases,307o to 75% of abnormal parathyroid glands arefound in a perithyroidal location, presumablyoverlooked or missed during the initial opera-tion.12'4s'46'61 Parathyroid adenomas in patients whohave failed initial operation are located in the ante-rior mediastinum in 20Vo to 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 in15% of cases. Of those located in the chest, posteriormediastinal ectopic adenomas are one-fifth as com-mon as anterior ones.s

The risks associated with reoperation outweighthe cost of preoperative imaging. In those patientswho are reoperated, the risk of vocal-cord injurybecause of damage to the recurrent laryngeal nerv-eor vagus nerve is approximately 77o compared withthe initial operating room risk of 1..3%.a6 When im-aging is not performed prior to reoperation for hy-perparathyroidism, surgery is approximately 60Voto707o successful; when imaging is performed prior

Figure 5. MR image of parathyroid carcinoma. A large softtissue mass (arrows) is seen anterolateral to the tracheaon the left side. The mass seems to be invading the inferiorplatysma-sternocleidomastoid musculature and invades ajugular vein (J). Histopathologically, this was a parathy-roid carcinoma.

to reoperation, the success rate increases to 80%to 90%.58 In reoperated cases, the sensitivities ofultrasonography (36-7 6V"),'n'45' 58' 77 scintigr aphy (26-g0 vo), z+, +s,so, sa cT (45_ 63%),24, 4s,s8, 77 and MR imaging(50-91Vo)'n'"'n5'56's8 have ranged widely. In a reviewof the literature, Price concluded that MR imagingwas the best cross-sectional imaging study to per-form in this scenario, and nuclear scintigraphy thebest functional examination.s8 The latest figures onsestamibi scintigraphy have shown sensitivities inthe range of 80% to90Vo.a1'e2Parathyroid hyperplasiais the most difficult diagnosis to make and accountsfor most false-negative studies.al e2 Nonetheless,Majors and colleagues found that sestamibi scan-ning identified parathyroid tissue in all nine pre-viously operated patients, including one with para-thyroid cancer.*t

By combining ultrasonography, CT, and scintig-raphy, one can increase the sensitivity rate to 78%,but at a high cost.as Although more invasive studieshave a greater yield, they are more demanding.Miller and colleagues' study found parathyroid ve-nous sampling (80Vo), intraoperative ultrasonogra-phy (787"), and arteriography (49-60Vo) Io havehigher sensitivity rates than the noninvasive im-aging studies.aa The expense and technical difficultyin performing these invasive examinations pre-cludes their routine use, but they may be held inabeyance for cases with equivocal or nonrevealing,noninvasive sfudies.

In the patient who has failed prior surgery for aparathyroid adenoma, both imaging and surgerymust contend with scar tissue in and around thethyroid glands, a loss of tissue planes, postoperativeinflammation, lymphadenopathy simulating para-thyroid adenomas, and distortion of landmarks.False-negative scans (caused by obscured anatomy)tend to occur in the perithymic or perithyroidaloperative beds. The incidence of false-positive ex-aminations (usually caused by lymphadenopathy)is lowest with nuclear medicine studies, followedby MR imaging, ultrasonography, and CT accordingto Mil ler and col leagues.as

Therefore, which study should one perform in thepreviously operated patient? Two camps of opinionhave formed. Sestamibi scintigraphy is probably themost accurate and affordable studv currentlv avail-able to identify parathyroid adenomas; its disad-vantage is that the surrounding anatomy is not visu-alized for surgical orientation. It alone or combinedwith ultrasonography or CT is an effective option.Alternatively, the most accurate (and most expen-sive) cross-sectional imaging technique is MR im-aging, which provides good anatomic detail, al-though it has the small risk of mistaking a lymphnode for an adenoma. Because re-reoperation is ananathema to the surgeon, multiple studies are notuncommonly performed if one is not definitive. Theidea of using a morphologic test (CT, ultrasonogra-phy, or MR imaging) and a functional test (ee-Tcsestamibi) is appealing. Use of this algorithm in-

PARATHYROID AND THYROID IMAGING 441

creases the reoperation success rate by more than30%.16

Secondary and TertiaryHyperparathyroidism

The evaluation of patients with secondary ortertiary hyperparathyroidism is rarely centeredaround the parathyroid glands because the kidneysare the source ofabnormality in these diseases. Para-thyroid glandular hyperplasia usually occurs in as-sociation with chronic renal failure and renal osteo-dystrophy. e-Tc sestamibi has been able to identifybilateral uptake in hyperplastic glands and residualparathyroid tissue in those individuals treated sur-gically in the neck for secondary hyperparathy-roidism.e3

Therapeutic Techniques

Ethanol ablation of parathyroid adenomas hasbeen performed under ultrasound guidance by per-cutaneous injection of absolute ethanol.sl' 71' 8e Thistechnique may be used in patients with primary orsecondary hyperparathyroidism who are not surgi-cal candidates because of medical illnesses. Approx-imately 0.5 mL to 1 mL of ethanol (95Vo) may beinjected at multiple sites within an adenoma witha22-gauge needle. The success of this technique ismonitored by following serial serum calcium levels;the technique may be repeated until normocalcemiais achieved.

Parathyroid Cysts

Cysts of the parathyroid glands are more com-mon in women than in men and mav be presentin the neck (Fig. 6) or anterior mediastinum. Atpresentation, they may be very large in size, andthe differential diagnosis may include thyroid cysts,thymic cysts, and necrotic lymph nodes. They usu-ally arise in the region of the inferior pole of thethyroid gland. They are virtually never found inchildren; most cases present in the fourth and fifthdecade of life.a0 They are usually unilocular, large,and may have hyperproteinaceous contents yield-ing high intensity on Tl-weighted MR scans. Theetiology may be congenital because of remnants ofpharyngeal pouches, or cysts may develop fromdegenerated parathyroid adenomas.

Hypoparathyroidism

The most common cause of hypoparathyroidismis iatrogenic removal of all functioning parathyroidtissue during surgery for hyperparathyroidism orthyroid disease. Primary idiopathic hypoparathy-

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Figure 6. A and B, MR images of parathyroid cyst.rounded cystic mass (arrows) with low intensity fluid.scan. This patient is status posfthryoidectomy.

A, Coronal T1-weighted scan demonstrates a@ The cyst (c) is bright on axial T2-weighted

roidism is a disease of childhood unassociated withcervical abnormalities. Pseudohypoparathyroidismmay be caused by renal disease; the serum parathor-mone (PTH) levels are paradoxically high becauseof a lack of renal responsiveness to the hormone.The glands may be normal or hyperplastic. In pseu-dopseudohypoparathyroidism, the calcium andphosphate levels are normal, although the physicalfeatures of pseudohypoparathyroidism (coarse fa-cies, dwarfism, mental retardation, round face,stubby fingers) may be present.

Imaging of parathyroid glands in patients withhypoparathyroidism is limited to the surveillancefor congenital absence, which is best accomplishedwith scintigraphic methods

THYROID IMAGING

The thyroid gland offers a multitude of interest-ing pathologic entities and lends itself to many dif-ferent imaging modali t ies. Depending on the cl ini-cal presentation and suspected abnormality, theclinician may order nuclear medicine scintigraphy,ultrasonography, CT, or MR imaging. The evalua-tion of an infant with a midline cystic mass in thelower neck is entirely different from that of a40-year-old man with a solid palpable nodule inthe thyroid gland. Once the anatomy and imagingoptions available to study the thyroid gland areunderstood, it is useful to divide thyroid lesionsinto neoplastic, congenital, and inflammatory cate-gories.

Anatomy

The thyroid gland is positioned anterolateral andsuperficial to the larynx and trachea and is fixed tothe airway by fibrous septa. Although no true lobesof the gland exist, it is enveloped by portions of

the deep cervical fascia. The thyroid isthmus is themidline portion of the gland and from it may arisea pyramidal "lobe" (50-807, of patients) lying su-periicial to the thyroid cartilage.;"

The vascular supply to the thyroid gland is de-rived from paired superior thyroidal arteries(branches of the external carotid arteries) and infe-rior thyroidal arteries (branches of the thyrocervicaltrunks of the subclavian arteries). The inconstantthyroidea ima arises directly from the aortic archand supplies a small inferior portion of the gland.The thyroid gland drains into superior, middle, andinferior thyroidal veins, which pass to internal jugu-lar and brachiocephalic veins. Vagal and sympa-thetic plexus branches provide innervation.

Histologically, the gland contains follicular cellsthat secrete the thyroid hormones and parafollicular("C") cells that elicit thyrocalcitonin. Interspersedwithin the gland one finds fibrous septa arid col-loid deposits.

lmaging Features of Masses

Ultrasonography

The main role of cross-sectional thyroid imaging(ultrasonography, CT, MR) is to evaluate thyioidmasses for_potential malignancy. Ultrasonogriphy,because of its simplicity, low cost, and adility todistinguish cystic from solid lesions is often theiirstmodality used to evaluate a thyroid mass in theeuthyroid patient. Good quality ultrasonographyrequires transducers that have 7.5 to 10 MHz fre-quencies.2o,7E These allow excellent detail of the su-perficial portions of the gland but enough penetra-tion to evaluate posteriorly to the level of the spine.When a solid leiion is hyperechoic, the incidenceof malignancy is only 4%.72 If a solid lesion is iso-echoic, the incidence of malignancy incre ases to 26Voand, if hypoechoic, malignancy occurs in 63%.72Pap-

illary carcinoma most commonly presents as a solidhypoechoic (77Vo) or isoechoic (14%) mass with orwithout calcification (calcifications are hvperechoicbut cause acoustic shadowing that is hypoechoic)(Fig. 7) .?'zIf a cancer is hyperechoic on ultrasonogra-

PARATHYROID AND THYROID IMAGING 443

phy, it is usually because of the sclerosing form ofpapillary carcinoma or medullary carcinoma.r6

If the margins of tumors on ultrasonography arestudied, 16% of malignant lesions will be found tohave sharply marginated, well-defined borders,

Figure 7. ,4-C, Ultrasonograms of papillary carcinoma. A, A reasonably well-defined soft tissue mass(M) is present surrounded by normal thyroid tissue. The mass is hypoechoic. Fine-needle aspirationrevealed papillary carcinoma. B, On transverse sonographic images of a different patient, a soft tissuemass (M) is identified that has internal heterogeneity to its echotexture. This mass was also a papillarycarcinoma of the thyroid gland. C, The longitudinal sonographic view of this mass (M) shows theabsence of an echopenic halo around the lesion and ill-defined inferior borders (arrows\.

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whereas irregular or ill-defined borders occur inapproximately 60% of cancers.T2 Unfortunately, ir-regular or ill-defined borders also occur in approxi-mately 45Vo of benign lesions.T2 When a mass has acomplete halo of echopenia around it, the lesion istwelve times more likely to be benign than malig-nant. If the halo is incomplete, a benign etiology isstill approximately four times more likely than amalignant one.72 Lesions meeting the absolute crite-ria for cysts (well-demarcated, smooth-walled, an-echoic, and demonstrating enhanced through-transmission) are usually benign.t6 A cystic lesionwith punctate, calcified mural nodules is indicativeof papillary carcinoma (Fig. 8).

Nuclear Medicine

A nuclear medicine studv may be another first-line imaging modality in a patieirt with a palpablethyroid mass. The agents used for thyroid imaginginclude 123I, 131l, ee'Tc pertechnetate, and 201T1. Thehalf-lives, whole-bodv radiation doses, and thvroidradiation doses are listed in Table 3.5& e0 Scanningis performed 15 minutes after administration of5 ti, 10 mCi of ee'Tc pertechnetate, 4 to 24 hoursafter administration of 100 to 400 p.Ci of 123I iodine,and 24 to 72 hours after administration of 30 pCiof r31I agents. With 'zolTl, scanning is performed 5 to10 minutes after thallium administration. Becausethe radiation energy of 131I is so high (364 keV), it isthe preferred agent for imaging substernal thyroid

Figure 8. Cyst and nodule. The ultrasonogram shows acyst with a nodule (arrow) protruding into the cyst. Notethe throughtransmission (arrowheads) from the cyst. Thiswas a colloid cyst with benign nodule. Calcification of themural nodule would make papillary carcinoma more likely.

glands or to perform whole-body imaging after thy-roid ablation to detect metastatic foci of thyroidcancer. The other agents have energies of 140 keV(ee-Tc) and 159 keV (123l).eo

The major role of scintigraphy in the evaluationof a thyroid mass is the determination of whetherthe lesion is hot (more uptake than the normal thy-roid gland), warm (some activity but not as much2ts the normal gland), or cold (little to no uptake).The risk of cancer in a hot nodule is between 1%and 4Vo, a warm nodule 8% and'l,jVo, and a coldnodule 15% and ZSVI (FiB. 9).se'0+,0t In a patient whohas a prior historv of head and neck irradiation. therisk oi malignanci itr a cold nodule doubles to 30%to 50%.58 Cold nodules in men have a higher rateof malignancy because women have a greater inci-dence of benign cold nodules from degenerated ad-enomas. If one performs dynamic injection ee-Tc

pertechnetate scintigraphy, one may find that hypo-perfused lesions (less vascularity than that of nativethyroid gland) are virtually never cancers, whereasmost malignancies are "euperfused" or hyperper-fused.35 Increased thallium uptake on both earlvand delayed scintigrams also iras been anecdotallyreported in thyroid malignancies.ra

Rarely, a lesion is cold on 123I scintigraphy buthot or warm on a e-Tc pertechnetate scan (a "discor-dant nodule"). It is beiieved that this phenomenonis caused by a lesion that traps iodine (assessed withpertechnetate) but does not organify it (the iodinescan). 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 acarcinoma (Fig. 10). Peripheral eggshell-like calcifi-cation and large multiple chunks of calcium suggestbenignity, whereas fine punctate calcification ismore indicative of malignancy.60 Calcification oc-curs in 13Vo of all thyroid lesions, including 17% ofall malignancies and 1,1,% of all benign processes.T2Similarly, cystic areas occur in many thyroidmasses; 38% of malignancies have cystic compo-nents, and 62Vo of benign masses may be entirelyor partly cystic.72 Hemorrhage may be found in pap-illary carcinomas or goiters. Multiplicity of nodulesin an enlarged thyroid gland usually suggests abenign process (or metastases).

The presence of lymphadenopathy or infiltrationof adjacent tissues suggests malignancy. More than50Vo of patients with papillary carcinoma havenodal spread at presentation, and 22Vo have occultthyroid tumors.a Curiously, the lymph nodes of thy-roid papillary carcinoma may show calcification,cyst formation, colloid accumulation, hemorrhage,or necrosis.T3'7a Sometimes the wall of a cystic nodemay be unidentifiable, thereby simulating a

PARATHYROID AND THYROID IMAGING 445

Table 3. SCINTIGRAPHIC AGENTS USED FOR THYROID IMAGING

Agent Half-life Total Body Dose (rads) Dose to Thyroid Gland (rads) Dose Administered

t-123t-125l -131Tc-99mTr-201

1 3 . 6 h60.1 d8.05 d6.02 h3 d

0.030.29

o.020.21

2-880-45030-1 00

0.04-2.0o.92

100-400 pCi PO30-1 00 pCi30-100 pCi PO5-10 mCi lV2-3 mOi lV

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

branchial cleft cyst. Papillary carcinoma of the thy-roid may metastasize to posterior triangle, subman-dibular, retropharyngeal, or jugular chain lymphnodes.73'74 The nodes mav enhance uniformlv anddramatically or, as with cystic or calcified nodes,not at all.73,7a Any lymph node seen in a patient withpapillary carcinoma is suspected of being malig-nant, no matter the size because of the relativelyhigh rate of lymphatic spread.

Enhanced CT has a maior drawback in the evalua-tion of thyroid lesions. Because of the iodine uptakefrom the contrast agent, thyroid localization withnuclear scintigraphy and radioactive iodine treat-ment must be delayed 4 to 8 weeks after administra-tion of iodinated contrast agents.

MR lmaging

Histologic specificity of thyroid lesions is not im-proved with MR imaging. The key to the diagnosisof thyroid cancer at MR imaging is the presence of

Figure 9. Cold nodule on scintigraphy. This ee'Tc pertech-netate scan demonstrates a cold nodule (arrows) in thelateral aspect of the left thyroid gland. A solitary cold nodulesuch as this one has a 15% to 25% chance of beino ma-l ignant.

malignant lymphadenopathy. Irregular margina-tion and clustered nodularity is characteristic, butnot specific for carcinomas (Fig. 11).18 Lesions thathave an intact and symmetric pseudocapsule areusually benign, whereas those with pseudocapsulesthat are penetrated or destroved are usually can-cers.18'52 Lesions that have capsules with irrbguhrthicknesses may be malignant or benign. On MRimaging, the nodes of papillary carcinoma may bebright or dark on Tl-weighted and T2-weightedscans, possibly related to the presence of intranodalhemorrhage or colloid accumulation.

Postoperatively, thyroid carcinoma recurren-ces are usually medium to high intensity on T2-weighted scans, whereas scar in the operative bedis usually low intensity.l Postoperative edema, in-fection, or hemorrhage may simulate recurrent tu-mor. 131I scintigrams are the best modality to evaluatethe operative bed and to screen for distant metasta-ses aiter thyroidectomy. MR imaging, in conjunc-tion with 131I radioisotope scanning, has been recom-mended for confusing postoperative cases.6

Fine-Needle Aspiration

Intimately associated with any imaging techniqueis fine-needle aspiration cytology. Many palpablelesions of the thyroid gland may be aspirated with-out imaging, but ultrasound is the most commonmodality used to guide aspirations because it im-ages in real time. Aspiration cytology in skilledhands yields outstanding results. In a series of11,000 guided and unguided samples performed atthe Mavo Clinic. the sensitivitv of the technioue wasfound io be 98% with a 99% positive pr"di.tin"value for cancer.le Nondiagnostic specimens werepresent in21% of cases, however. Using fine needleaspiration with ultrasound guidance yields resultsof 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.The most common histologic subtype is papillarycarcinoma that accounts for 55% to 80% of thyroidmalignancies.3e' 58' 78 Although follicular elements ina papillary carcinoma are common, and this hasled to a "mixed papillary-follicular" or "follicular

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Figure 10. A and B, CT scans of papillary carcinoma. A, This enhanced CT scan demonstrates amass (M), which has irregular calcification within it, in the left side of the thyroid gland. The presenceof lymph nodes (arrouvs) is highly suggestive of papillary carcinoma. & This cystic lesion with peripheralcalcification in the wall (arrowy proved to be a degenerated adenoma.

Figure 11. A-D, Papillary carcinoma on MR scans and scintigraphy.4, Axial T1-weighted scandemonstrates a hyperintense mass (M) with peripheral hypointensity representing calcification. Thewafl, however, is not intact at its anterior-most border (arrows\. The remainder of the gland showsdiffuse enlargement with heterogeneous signal intensity compatible with goiter. The patient presentedwith an enlarging right-sided thyroid mass. 4 Post-gadolinium-enhanced scan demonstrates minimalenhancement because it was bright on pregadolinium T1-weighted scans. No invasion of adjacentstructures was identified. C On T2-weighted scan, the border, though irregular, seems to be intact.Note that on the left side, the signal intensity of the goiterous thyroid gland is inhomogeneous.D, Scintigraphy of this mass revealed bilateral cold areas (C) within the thyroid gland with only a centralarea (arrows) of relatively normal uptake. Biopsy revealed papillary carcinoma of the thyroid gland.This shows how a benign appearance can be present with malignancies of the thyroid gland.

variant" histologic classification, the "mixed can-cer" ultimately behaves like a papillary carcinoma(vide infra). Purely follicular carcinoma occursin 5% to 15%. Anaplastic carcinoma represents 3%lo 10% of all malignancies, with m-edullary orHurthle's cell carcinoma accounting for 4Vo lo5Vo.1e'3e Medullary carcinoma may present in associ-ation with the multiple endocrine neoplasia syn-dromes (see Table 2) and serologically may expresscalcitonin. The other histologic diagnoses to con-sider in thyroid malignancies are non-Hodgkin'slymphoma and metastases.

Imaging has a well-defined role in the workupof the patient with a solitary nodule in the thyroidgland. Unless a classic appearance of a benign con-dition is present, however, pathologic sampling isrequired. This is because the appearance of thyroidmalignancies may simulate many benign processes,and vice versa. The specificity of imaging findingsis low.

The detection and characterization of a thyroidneoplasm is not the only role of imaging. Imagingshould also evaluate for infiltration of the adiacentsoft tissue, aerodigestive tract, paraspinal muscula-ture, and carotid arteries. The presence or absenceof adenopathy is also important for prognostic im-plications with thyroid cancer.

Papillary Carcinoma

The presence of psammoma bodies (laminatedcalcific spherules in25-40Vo of cases), ground glassnuclei, and a branching pattern with a fibrovascularpapillary stroma are the histologic signatures ofpapillary carcinoma of the thyroid gland.3e As notedearlier, follicular growth patterns may coexist. Cystformation (cystadenocarcinoma), encapsulation,multifocality, and anaplasia may be present withina thyroid gland with papillary carcinoma.

Papillary carcinoma is the thyroid malignancythat has the greatest likelihood of spread to lymphnodes; the nodes may be tiny, cystic, hemorrhagic,or calcified (Fig. 12). The incidence of nodal metasta-ses during diagnosis is50%, whereas distant metas-tases are reported to occur in 4Va to 7Vo, usu.ally tothe lungs, bone, or central nervous system.3e Despitethese features, the 2O-year survival rate is reportedto be as high as 90%. Approximately 10% of papil-lary carcinomas are bilateral.ea

Follicular Carcinoma

Pure follicular carcinoma is relatively uncommonwhen the follicular variant of papillary carcinomais excluded. The tumor mav be diffuselv invasiveor well encapsulated. Follicular carcinorna less fre-qently spreads to lymph nodes (2-10%) than doespapillary carcinoma, but disseminates hematoge-nously more readily.3e The prognosis depends onthe presence of hematogenous metastases or localinvasiveness but is not as optimistic as that for papil-

PARATHYROID AND THYROID IMAGING 447

lary carcinoma. No distinguishing features on im-aging studies suggest this diagnosis as opposed toother cancers, although, on ultrasonography, follic-ular carcinoma is isoechoic in 52% and hypoechoicin44Vo.20'72 Compared with papillary carcinoma, fol-licular carcinoma rarely becomes cystic and morefrequently invades vessels.3e

Anaplastic Carcinoma

This type of cancer is one of the most aggressivemalignancies of the head and neck with prognosesmarked in months rather than years. Older patientsare usually affected. Anaplastic thyroid carcinomasoccur within a substrate of goiters in 47Vo of cases3eand often coexist with other forms of better differen-tiated thyroid cancer. The outcome in mixed tumorcases is dominated by the poor prognosis of ana-r:lastic carcinoma.^

On ultrasonography, these carcinomas are mostcommonly hypoechoiq20,D,72 whereas on CT, ana-plastic carcinomas show evidence of dense amor-phous calcification in SBVo of cases and necrosis in74Vo.u Metastatic lymph nodes are present in 74Voto 80% of cases and show necrotic areas 50% of thetime.e'82 Invasion into carotid arteries or adjacentaerodigestive structures occurs in 34% to 55% ofpatients, and in 25Vo the primary tumor extendsinto the mediastinum (Fig. 13).q8'?Rapid growth andobliteration of adjacent tissue planes are hallmarksof this deadly tumor with a median survival ofapproximately 7 months.

Medullary Carcinoma

Medullary carcinoma originates in the parafolli-cular or "C" cells of the thyroid gland, cells derivedfrom neural crest tissue in the ultimobranchial bod-ies of the branchial pouch system. These cells nor-mallv secrete thvrocalcitonin, which decreases se-rum'calcium. Eiahty percent to 90% of medullarycarcinomas express calcitonin. Functioning tumorshave a better prognosis.q

Medullary carcinomas are usually hypoechoic onultrasonographyzo' zz' 72; however, echogenic focicaused by deposits of calcium may be seen withinthese tumors and metastatic lymph nodes whenpresent.22 These tumors usually do not take up io-dine but may be thallium or gallium avid. Somato-statin receptor scintigraphy also may detect medul-lary carcinoma.ll The tumor is solid on CT and MRimaging and spreads to lymph nodes in more than50Va of cases (Fig. 14).

Medullary carcinoma has a familial incidence of"lOVo to 20Vo. Sipple syndrome is the association ofmedullary carcinoma with pheochromocytoma andparathyroid adenoma or hyperplasia. This is alsoknown as the MEN 24. When mucosal neuromasand marfanoid facies coexist, MEN 28 is said to bepresent (see Table 2). Both syndromes have beenlocalized to an abnormal gene on the tenth chro-mosome.

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Figure 12. 4-E, Metastases of papillary carcinoma. A, This postcontrast axial CT scan shows twohypodense lymph nodes (n) on the right side of the neck from papillary carcinoma" 8, Note that thepatient had diffuse metastases to the lungs represented by multiple miliary-like nodules. C, In a differentpatient, a densely enhancing lymph node (n) on the left side is seen deep to the sternocleidomastoidmuscle. D, This patient had a cystic and sotid fymph node metastasis (arrows) from the primary thyroidcarcinoma (c). E, T1-weighted MR scan shows a hyperintense node (arrow) from colloid, hemorrhage,thyroglobul in, or high protein.

Lymphoma

Thyroid lymphoma may present as a solitarymass (80%) or as multiple nodules (20%).81 An ante-cedent history of Hashimoto's thyroiditis in an el-derly female with a rapidly enlarging, compressive,and infiltrative mass suggests lymphoma. Mostare B-cell neoplasms.3e Response to chemotherapyand radiation is variable; some patients do verywell.

Lymphomas are usually hypoechoic at sonogra-phy-z0 z-z t2 Lymphoma is iold bn technetium or"io-dine nuclear medicine studies; however, galliumscans may show increased activity. Other lympho-prol i ferat ive ( leukemia) and granulomatous'dis-eases (e.9., sarcoidosis) also may be gallium avidand are in the differential diagnosis. The tumor ishypodense on unenhanced and enhanced CT stud-ies and shows necrosis or calcification in only 7%of cases (Fig. 15).81 Invasion of the carotid sheath

Figure 13, Anaplastic carcinoma on CT scan. Diffuse en-largement with inegular contrast enhancement is noted inthe thyroid gland of this patient with anaplastic carcinoma.The predominant density is hypodense to the native thyroidtissue. One would expect to see marked enhancement inthe normal thyroid gland due to iodine accumulation.

(19-51,7") or metastases to lymph nodes (1,4-44Vo)are not uncommon.8l The absence of calcificationand necrosis, the rarity of invasion into surroundingsoft tissues, and the lower incidence of nodal dis-semination help to distinguish lymphom a fuom ana-r:lastic carcinoma.^

Lymphoma is usually homogeneously hyperin-tense on T2-weighted MR scans. Although someworkers have found Hashimoto's thyroiditis to below in intensity on T2-weighted images and, there-fore, distinguishable from lymphoma (which isbright),6e most investigators have found their signalintensities to overlap.18, 55' 57

Metastases

Metastases to the thyroid gland are often clini-cally occult. Pathologicallp metastases to the glandmay be present in2% to 4Vo of patients dying frommalignant disease.66 The two most commonprimarytumors to metastasize to the thyroid gland are bron-

PARATHYROID AND THYROID IMAGING 449

Figure 1 5. CT scan of thyroid lymphoma. Diffuse infiltrationof the left thyroid gland is noted on this contrast-enhancedexaminalion.

chogenic carcinoma and renal cell carcinoma. Multi-focality is the norm (Fig. 16), and hemorrhage isnot uncommon with renal metastases.

Benign Masses

F u nction i ng Thyroi d Ade nom as

More than ninety percent of solitary hot noduleson scintigraphy are benign in etiology, usually ade-nomas or hyperplasias that are expressing thyroidhormone. Plummer's disease is hyperthyroidism re-sulting from a solitary autonomous hot nodule (Fig.17).58 The difference between an autonomous anda hypertrophic functioning hot nodule depends onthe response to a thyroid suppression test. After adiagnostic course of thyroid hormone administra-tion (with confirmation of depressed thyroid stimu-Iating hormone [TSH]), a lesion that is persistentlyhot on a eemTc pertechnetate scan is considered anautonomous lesion, whereas one that becomes coldis considered hypertrophic.un Other sources of hot

Figure 14. A and B, Medullary carcinoma of the thyroid gland. l, This patient has a thyroid mass (.)on the right that has invaded the tracheal wall accounting for the thickening (arrows) seen lateral tothe endotracheal tube. lt was medullary carcinoma. B, Note absence of right lateral tracheal wallfurther down.

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Figure 16. Metastatic renal cell carcinoma to the thyroidgland. The multiple masses in this enlarged thyroid glandwere caused by metastases from a primary renal cell carci-noma. Because the thyroid gland absorbs so much iodin-ated dye, they appear as filling defects amidst the gland.

nodules include thyroiditis, normal variation in thy-roid function, and ectopic tissue.58

"Toxic" adenomas rarely cause clinically appar-ent hyperthyroidism until they exceed 2.5 cm insize.16 The patient usually presents with a slowlygrowing neck mass. The imaging features of toxicadenomas are nonspecific on nonscintigraphic mo-dalities. The lesions are usually solid and en-hancing.

N onfu nction i ng Thy roi d Ade n omas

A cold (nonfunctioning) nodule is approachedmore aggressively than a hot nodule because ofthe higher rate of malignancy, especially in youngwomen and in men of all ages. A biopsy or aspira-tion is often required early in the diagnostic algo-

Figure 17. Hot nodule on nuclear scintigraphy. Note in-tense update of radiotracer in this functioning adenoma(arrow). The remainder of the gland shows relatively littleuptake owing to the suppression incurred by reduced TSHfrom the outpouring of thyroid hormone by the "toxicnodule."

rithm. The majority of cold nodules are caused bydegenerated (follicular) adenomas (Fig. 18) nodularhemorrhage, cysts, goiters, inflammatory condi-tions (see subsequent discussion), or amyloid depo-sition.6a Follicular adenomas occur in all age groups,in women more than in men, and are usually lessthan 3 cm in size. As adenomas outgrow their bloodsupply, they may involute or encyst. Alternatively,they may develop intralesional hemorrhage (andacutely expand), necrosis, calcification, or scarring.Malignant degeneration is not believed to occurin adenomas.

Hurthle's cell adenomas (which some investiqa-tors believe are malignant in character) are morevariable in size and shape with less well-definedborders.

Occasionallp one will find a hyperplastic ade-noma that is responsive to TSH in a patient withGrave's disease. this appea.s as a cold nodule be-cause the hyperthyroidism of Grave's disease sup-presses TSH, which in turn suppresses the adenomaon a nuclear medicine studv. This entitv is calledMa r i n e- Le nha r t sy nd ro me.oa

In one of the earliest articles on the subiect of MRimaging, Gefter and colleagues identified adenoma-tous nodules as small as 4 mm to 5 mm in size.l8They noted that follicular adenomas appeared aswell-circumscribed nodules with heterogeneous in-tensity, bright on T2-weighted images (Fig. 19).

Cysts

Most thyroid cysts actually represent degenera-tion of adenomas. Cysts of any kind are anechoicor echopenic on ultrasonography, show a distinctback wall, and demonstrate enhanced through-transmission. They are low density on CT unlesshemorrhagic or infected. The density and intensityof the cyst mav not simulate that of cerebrospinalfluid on CT anci trrtR imaging because of the p.esen"eof hyperproteinaceous colloid within the cyst. Col-Ioid cysts are characterizedby homogeneous high-signal on Tl-weighted scans6a; however, this findingis not specific to colloid cysts because areas of hem-orrhage, also bright on Tl-weighted scans, can beseen in goiters, adenomas, and traumatized cysts.Even thyroglossal duct cysts (vide infra) may behyperintense because of high protein content.

Multinodular Goiter

Another common palpable thyroid abnormalityis the multinodular goiter. A goiter is simply anenlarged thyroid gland that may be seen with hy-perthyroidism or hypothyroidism. In the UnitedStates, the common vernacular is to imply a non-toxic goiter when the term is used. A euthyroidor hypothyroid goiter is the most common thyroidlesion in the United States. Patients, usually olderwomen, present because of hypothyroidism, neckmasses, or tracheal-esophageal compression. In rare

PARATHYROID AND THYROID IMAGING 45'],

Figure 18. A and B, Cold nodule. A, A cold nodule was seen along the lateral aspect of the left sideof the thyroid gland (arrow) on this anteroposterior view. B, The MR scan demonstrates two lesionson this slice that were adenomas in a multinodular goiter. In retrospect, the other lesion could be seenposteriorly on the oblique scintigrams.

instances, a previously nonfunctioning multinodu-lar goiter evolves into one with hyperfunctioningnodules and causes hyperthyroidism. The incidenceof carcinoma in a multiodular goiter is very low(below 3%) and the characteristic appearance ofmultiple cold areas interspersed with hot areas in alarge gland usually obviates the need for aggressivebiopsy of a palpable nodule (Fig. 20).6a A large,dominant, hard, or growing mass amidst a goitershould probably still be biopsied (see Fig. 1).70

Nontoxic multinodular thyroid glands show min-imal to moderate heterogeneity with nodularity andmildly increased signal intensity on T1-weightedMR image.l& s2 Hemorrhagic foci are noted in 60%of cases and the lesions are often heterogenous onT2-weighted scans.s2 Goiters usually dJnot havepseudocapsules.s2 On CT and ultrasonography,

mixed solid and cystic zones within an enlarged,nodular thyroid gland with or without calcificationis the characteristic appearance of a multinodulargoiter (Fig. 21).

Teratomas

These are rare neoplasms of the thyroid gland.As in other locations in the body, thyroid teratomasmay demonstrate fluid, fat, c;lcificatiory and os-seodental densities in various combinations. Theyusually occur in the midline.

Hyperthyroidism

The three most common causes of hyperthyroid-ism are Graves' disease (diffuse toxic goiter), toxic

Figure 19. A and B, MR images of a thyroid adenoma. A, Note the inhomogeneous signal intensityin this hemorrhagic mass (M) on this T2-weighted fat-suppressed MR scan. B, On T1-weighted scan,one sees high signal intensity within the central portion of the mass. lt may be unclear as to whetherthis represents colloid material, hemorrhage, or hyperproteinaceous secretions. The capsule aroundthe lesion (arrows) seems to be well defined, except at its anteromedial aspect.

452 YOUSEM

. . , ,

. . , . i

r i : r i r : : i " l l ' : ' : : '

Figure 20. Goiter. Nuclear scintigraphy demonstrates anenlarged inhomogeneous thyroid gland. Multiple cold areasare present as well as warm areas and hot areas withinthis gland.

multinodular goiter, and toxic adenomas. The toxicadenomas (discussed earlier) are separated intothose that are TSH-responsive (hypertrophic) orTSH-independent (autonomous). Occasionally, in-flammation of the thyroid gland (thyroiditis) pro-duces a transient state of hyperthyroidism. On rareoccasions, ectopic thyroid tissue (lingual or ovarian)causes hyperthyroidism.

Intenzo and colleagues have proposed a uniquealgorithm for evaluating a hyperthyroid patient.3OIf thyroid function tests (TFTs) are elevated and the24-hour radioactive iodine uptake (RAIU) is alsoelevated (normal, below 357"), the differential diag-nosis is Graves' disease or Marine-Lenhardt disease

(Graves' with coexistent TSH-dependent nodules).The latter appears on scintigraphy as a gland withdiffuse increased trapping of the radiotracer withsuperimposed cold nodules. If the TFTs are elevatedbut the RAIU is normal, one should consider Plum-mer's disease (hyperthyroidism due to a solitaryautonomous hot nodule that suPPresses the remain-der of the gland), Graves' disease with rapid iodineturnover, or a laboratory error.m If TFTs are elevatedbut RAIU is depressed, the possibilities include sub-acute granulomatous thyroiditis, subacute lympho-cytic thyroiditis, postpartum thyroiditis, andstruma ovarii. With thyroiditides, thyroid hormonemay escape ruptured follicles leading to transienthyperthyroidism, although the damaged gland can-not concentrate iodine so the RAIU and thyroidscans show depressed uptake.3o

Graves' Disease

Graves' disease is the most common cause of hy-oerthvroidism. This disease affects women moreiommonly than men and a familial tendency is pres-ent. Patients may have heat intolerance, weight loss,fatigue, insomnia, tremors, palpitations, increasedthirst and hunger, and agitation. Exophthalmosmay be present, although thyroid eye disease neednot occur only in the setting of hyperthyroidism; itmay be present post-therapy when the patient iseuthyroid or even hypothyroid. Blood tests are usu-ally able to make the diagnosis of Graves' diseasebecause of the autoimmune phenomenon associ-ated with the disease. Thyroid-stimulating immu-noglobulins, such as long-acting thyroid stimulator,simulate the function of TSH and cause hyperthy-roidism. On iodine scans, there is markedly elevatediodine uptake within a nonfocal, hot, enlarged thy-roid gland.

Figure 21. Ultrasonography and CT scan of goiter. A, This ultrasound examination reveals multiplenodules (arrows\ seen as hypoechoic areas within an enlarged thyroid gland. 4 In a different patient,one can see bilateral enlargement of the thyroid gland with a hypodense central area on the left side andirregularity and inhomogeneity on the right side. The gland is enlarged and, curiously, is predominantlyposterior to the airway.

In a patient who is hyperthyroid, scintigraphymay be useful in distinguishing Graves' disease,which shows homogeneous diffuse intense uptake(70-85%) from thyroidltides (FiB. 22). Thyroiditisis less homogeneous and the uptake may be normal,high, or low depending on the state of the inflam-matory process. Because some thyroiditides (seesubsequent discussion) may revert to euthyroid ac-tivity with time, the implications for theiapy areimportant; Graves' disease requires antithyroidmedication, radioactive iodine obliteration of thegland, or surgery. Thyroiditides are treated conser-vatively.

Diffuse glandular enlargement with avid en-hancement may be noted on CT and MR imagingin patients with Graves' disease. A large pyramidallobe often coexists. Carcinoma of the thyroid glandin a patient with Graves' disease is rare, reportedin only 0.157o to 0.5Vo of patients.l0

Hypothyroidism

Hypothyroid patients have cold intolerance; fa-tigue; apathy; weight gain; bradycardia; constipa-tion; edema; macroglossia; and poor condition ofthe hair, nails, and skin. Women are affected morefrequently than men. The response to thyroid hor-mone replacement is excellent.

Hashimoto's thyroiditis is the most commoncause of hypothyroidism in the United States (seesubsequent discussion). Worldwide, iodine defi-ciency (endemic goiter) is another cause of hypothy-roidism but is infrequently seen in developed coun-

Figure 22. Graves' disease on nuclear scintigraphy. Thisgland was enlarged and showed increased radiotracer up-take. Note the pyramidal lobe (arrows), which is also en-larged.

PARATHYROID AND THYROID IMAGING 453

tries. Other etiologies include the other chronicthyroiditides. Postoperative and postradiotherapy(131I or external beam irradiation) patients also ac-count for more hypothyroid patients. It is commonfor patients treated with radioactive iodine for hy-perthyroidism to become hypothyroid after sev-erar years.

Congenital hypothyroidism occurs more com-monly in the Japanese population (1 in 5500 new-borns).83 Possible causes include thyroid aplasia,hemiaplasia (the left gland is absent more com-monly than the right), or ectopia (80%), dyshormo-nogenesis (10-1,5%), pituitary or hypothalamic de-ficiency (< 5%) and autoimmune disease (< SVo).Prompt replacement of thyroid hormone is criticalbecause mental retardation is a possible complica-tion of undiagnosed neonatal hypothyroidism.83Both ultrasonography and scintigraphy are used toidentify thyroid tissue in this population.

Congenital Lesions

Thyroglossal Duct Cysts

Two of the most common congenital abnormali-ties associated with the thyroid gland are thyroglos-sal duct cysts and lingual thyroid glands. The thyro-glossal duct cyst is a congenital lesion in which thetract of migration of the thyroid gland from theforamen cecum of the tongue (located in the midlineat the circumvallate papillae level) to the normalposition of the thyroid gland is persistent. Althougha congenital lesion, 50% of cases present after age10 years. Any epithelial-lined tract has the potentialfor obstruction and a cyst may occur due to retainedsecretions. In thyroglossal duct cyst, a midline cysticmass is observed, which is located in an infrahyoidlevel in 65V", hyoid level in 1,5%, and suprahyoidlevel in 20Vo of cases.3 It mav occur in a paramedianposition in 25Vo of cases, usually in the infrahyoidcompartment. The stereotypical locations of the thy-roglossal duct cyst are embedded in the strap mus-cles below the hyoid bone, or at the midline junctionof the hyoid bone above the strap muscle insertions(Fig. 23).

Because the fluid in the thyroglossal duct cystmay have a high protein content, it may appearcystic with some internal echoes on ultrasonogra-phy. It moves with swallowing or sticking thetongue out. On CT, the noninfected thyroglossalduct 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 beeither dark or bright on Tl-weighted scans but istypically hyperintense on T2-weighted scans. En-hancement is uncommon in thyroglossal duct cystsunless the lesion has been traumatized or infected.In those instances, peripheral rim enhancementmay occur.

454 YOUSEM

Ectopic thyroid tissue is found in approximately25Vo to 33% of thyroglossal duct cysts.3'27 The inci-dence of carcinoma within the thyroid tissue of athyroglossal duct cyst is less than

'l.Vo.3'27 Y,lhen 1t

occurs, it is usually papillary carcinoma.Recurrence rates of approximately 4% are ob-

served after attempted removal of thyroglossal ductcysts.26 The surgery removes the entire tract of theduct including the middle one fourth of the hyoidbone and a portion of the base of the tongue thatincludes the foramen cecum (Sistrunk procedure).23

Rarely, the tract of the thyroglossil duct mayserve as conduit for infection to the thyroid glandleading to acute suppurative thyroiditis.3'?

LingualThyroid Glands

Lingual thyroid tissue occurs in 1 in 3000 patientswho have thyroid disease and represents the mostcommon form of functioning ectopic thyroid tis-sue.66It is also the most common benign mass foundat the circumvallate papillae. The lingual thyroidgland represents arrest of migration of the thyroidtissue within the tongue, usually in the midline be-tween the circumvallate papillae and the epiglottis.This may be a complete arrest or incomplete arrestof migration. Lingual thyroid glands are associatedwith absence of thyroid tissue in the neck in 70%lo 80Vo of cases and are seen much more commonlyin women.6'23'66 Patients often present in puberty,when the tissue may expand rapidly. Variation insize with menstruation also has been reported.

The primary role of imaging is to identify whethernormal thyroidal tissue is present in the lower neckso that complete excision or transplantation of thelingual thyroid tissue may be contemplated. If noother thyroid tissue is present, the patient is con-signed to lifelong thyroid replacement therapy if thelingual thyroid gland is totally removed. A nuclear

Figure 23. A and B, Thyroglossal duct cyst. A, A cyst embedded in the strap muscle can be seen onthis T2-weighted MR scan" Note the tract (arrows) extending from the midline to the right lateral positionin this paramedian thyroglossal ductal cyst. B, A different patient had a hyperintense midline thyroglossalductal cyst (arrows) on this T1-weighted scan.

medicine study to determine whether a lingual massrepresents thyroid tissue, and also to search forother (ectopic or normally located) thyroid tissue, isfavored over cross-sectional imaging. The thyroidaltissue within the tongue can be identified by its highattenuation on CT (due to iodine accumulation) orits avid contrast enhancement. In a similar fashion,the MR scan demonstrates bright tissue that avidlyenhances in the middle of the tongue.

A malignancy arising within a lingual thyroidgland is more common than one in a thyroglossalduct cyst. At least one report noted an incidenceof 2.8%.aB

Aberrant Thyroid Tissue

Thyroid tissue lateral to the jugular vein unassoci-ated with lymphadenopathy may occur due toanomalous development and is termed lateral aber-rant thyroid tissue. This phrase is rarely used noqbecause most cases of lateral aberrant thyroid tissueactually represented thyroid carcinoma metastasesto lymph nodes. Nonetheless, in rare instances, thy-roid tissue may be "seeded" to this location bytrauma, surgery, thyroiditis, or goiters, and must bedistinguished from metastatic thyroid carcinoma.

Undescended thyroid tissue sometimes may beseen in the anterior neck superficial to the hyoidbone. Aberrant thyroid tissue also may be found inthe trachea. In this site, women are affected morecommonly than men, and the thyroid tissue mayresPond to hormonal influences.

Substernal thyroid tissue is not uncommon butusually occurs in association with a goitrous glandextending downward rather than as isolated tissue.Tracheal or esophageal compression on a chest ra-diograph may be the presenting finding. Imaging todistinguish a goiter from mediastinal adenopathy,thymoma, Iymphoma, teratoma, carcinoma, or an

unusual bronchogenic cyst is usually pursuedwith CT.

Struma ovarii, the presence of functioning thy-roid tissue in the ovaries or in an ovarian teratomaor dermoid, is rare.

Inflammatory Lesions

No specific scintigraphic, sonographic, CT, or MRappearances differentiate among the various in-flammatory processes involving the thyroid gland.The most useful imaging study is the nuclear medi-cine scan, performed with ee'Tc pertechnetate orradioactive iodins (tzal or 131I), which determinesthe activity of the thyroid gland. The value of theimaging studies, however, pales in comparisionwith that of serology for distinguishing various in-flammatory lesions of the thyroid gland. On theother hand, if imaging is to be used as a map forsurgical correction or resection of the thyroid gland,MR imaging and ultrasonography seem to be ofparticular benefit. In some instances, the adminis-tration of iodine on an enhanced CT scan mightprecipitate thyroid storm (acute outpouring of thy-roid hormone), so CT usually is avoided.

Suppu rative Thyroiditis

Acute suppurative thyroiditis presents with acuteonset of pain and swelling in the thyroid glandassociated with fever, odynophagia, and dyspha-gia.25 The role of imaging is to exclude a pyriformsinus or thyroglossal duct fistula as an etiology forthe acute suppurative thyroiditis. This entity occurssometimes in association with a fourth branchialcleft anomaly and has a left-sided predominance.2sImaging may identify leakage from the pyriformsinus to the lateral neck at the thyroid gland level.Acute suppurative thyroiditis is the rarest form of

PARATHYROID AND THYROID IMAGING 455

thyroiditis but has the most fulminant clinical pre-sentation.

Hashimoto's Thyroiditis

Most other forms of thyroiditis are subacute orchronic diseases. Hashimoto's (chronic lymphocyticthyroiditis) is the most common of the chronic thy-roiditides, being five to ten times more frequentthan subacute thyroiditis.s8 It is the most commonthyroiditis in children. The diagnosis is based onserology because the disease is an autoimmune pro-cess with antigenic stimulation to thyroglobulin,colloid, and other thyroid cell antigens. Serum levelsof antimicrosomal antibodies are elevated andFNAs may reveal a preponderance of lymphocytes,centroblasts, and Hurthle's cells.el Women are af-fected nearly 20 times more frequently than men,and the chief complaint is usually enlargement andtenderness of the thyroid gland. Hypothyroidismis present at presentation or develops later in 50%of cases.

The gland with Hashimoto's thyroiditis is en-larged and shows multinodularity and heteroge-neous increased or decreased uptake of radiotrac-ers. Although early in the disease there may beincreased uptake of iodine on nuclear medicinestudies, the usual response is diminished or normalthyroid uptake on imaging.el Patients who trapmore tracer have a greater chance of returning to aeuthyroid state than those who do not. AlthoughHashimoto's thyroiditis shows no greater risk forcarcinoma, it seems to predispose to non-Hodgkin'slymphoma.sl Hashimoto's thyroiditis in the pres-ence of thyroid lymphoma is seen In 25% to 67Voof cases.e'81

On ultrasonography, the thyroid gland is sym-metrically enlarged and hypoechoic but may havenodules within it (Fig. 24). Calcification is seen inthe chronic stages. On T2-weighted scans, MR im-

Figure 24. A and B, Hashimoto's thyroiditis on ultrasonography. 4, Sagittal scan through the right lobeshows an enlarged gland with some nodularity (arrows) to it. B, The transverse view also depicts aprominent irregular gland.

456 YOUSEM

aging has shown increased signal intensity, some-times with linear low intensity bands thought torepresent fibrosis.18, 57

Hashimoto's disease has been associated withother autoimmune entities, such as pernicious ane-mia, Sjogren's syndrome, lupus, rheumatoid arthri-tis, Addison's disease, and Graves' disease.

Riedel's Thyroiditis

Reidel's thyroiditis (struma thyroiditis) is an un-common chronic inflammatorv lesion of the thvroidgland and neck. The disease may be bilateial orunilateral and is more common in women than inmen. Patients present with evidence of mass effectwith compression of the trachea, hoarseness, anddifficulty ln swallowing. The patients are usuallyhypothyroid. On imaging, Riedel thyroiditis is ho-mogeneously hypoechoic on ultrasound and is usu-ally hypodense to normal thyroid tissue on CT.20.s7The lesion may be isodense to muscle on unen-hanced CT. Riedel thyroiditis may spread to outsideof the thyroid gland, infiltrating and obliteratingadjacent tissue planes (Fig. 25). The characteristicfinding on MR images is hypointensity on T1- andT2-weighted sequences with infiltration of adjacentstructures of the neck.sT The low intensity on MRimages is believed to be caused by the fibrotic natureof the disorder. This lesion may be associated withretroperitoneal fibrosis, mediastinal fibrosis, scle-rosing cholangitis, and orbital pseudotumor. It isdistinguished from Hashimoto's thyroiditis, whichis typically increased in intensity on T2-weightedMR images.

de Queruain's Thyroiditis

de Quervain's thyroiditis (subacute thyroiditis)is a disease of middle age occurring most commonlyin women after an upper respiratory infection. Cox-sackie, ECHO, and mumps viruses have been impli-

Figure 25. A and B, Riedel's thyroiditis. ,4, This thyroid "mass" has infiltrated the subglottis, causingthickening of the mucosa. Obliteration of the fat planes between thyroid gland and right side of esophagusalso is present. B, AI a more inferior level, one can see the diffuse infiltrative nature of the lesion intothe tracheal rinos.

cated.3e Pain, fever, and fatigue are common pres-enting symptoms. Subacute thyroiditis may present(50% of cases) with acute toxic hyperthyroidismwith subsequent return to a euthyroid state after1 to 2 months.66 Hypothyroidism occurs approxi-mately 2 to 4 months after onset and, typically by6 months after the acute onset, the patient revertsto euthyroidism.s8 Patients are treated medically be-cause the prognosis is good for return of normalthyroid function. Subacute thyroiditis is hypoechoicon ultrasonography, although there may be atrophyof thyroidal tissue with time.20 Nuclear medicinestudies show heterogeneous uptake that varies ac-cording to the stage of the disease.

Miscellaneous

External beam radiation may cause a chronic thy-roiditis associated with fibrosis. In low doses (usedin years past for radiating the thymus, adenoids,acne/ or ringworm), radiation predisposes to papil-lary carcinoma. Radioactive iodine treatment alsocauses severe fibrosis and atrophy of the gland.

Amyloidosis and hemochromatosis may affectthe thyroid gland and lead to decreased signal inten-sity on T2-weighted MR scans.

Tuberculosis, sarcoidosis, and fungal infectionsmay cause a granulomatous inflammation of thethyroid gland but are uncommon conditions.2

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