ORIGINAL ARTICLE

USEFULNESS OF THE COMBINATION OFULTRASONOGRAPHYAND 99MTC-SESTAMIBI SCINTIGRAPHYIN THE PREOPERATIVE EVALUATION OF UREMICSECONDARY HYPERPARATHYROIDISM

Carlo Vulpio, MD,1 Maurizio Bossola, MD,1 Annamaria De Gaetano, MD,2 Giulia Maresca, MD,2

Isabella Bruno, MD,3 Guido Fadda, MD,4 Francesca Morassi, MD,4 Sabina C. Magalini, MD,1

Alessandro Giordano, MD,3 Marco Castagneto, MD1

1 Istituto Clinica Chirurgica, Universita Cattolica del Sacro Cuore, Rome, Italy. E-mail: c.vulpio@alice.it2 Istituto di Radiologia, Universita Cattolica del Sacro Cuore, Rome, Italy3 Istituto di Medicina Nucleare, Universita Cattolica del Sacro Cuore, Rome, Italy4 Istituto di Anatomia Patologica, Universita Cattolica del Sacro Cuore, Rome, Italy

Accepted 20 October 2009Published online 20 January 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21320

Abstract: Background. The usefulness of the combination

of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI)

parathyroid scintigraphy and ultrasonography to detect para-

thyroid glands (PTGs) in secondary hyperparathyroidism

(SHPT) is still controversial.

Methods. In all, 21 patients with SHPT underwent parathyr-

oidectomy. The sensitivity and specificity of ultrasonography

and scintigraphy related to site, size, hyperplasia type of PTG,

concomitant thyroid disease, and the frequency of intraopera-

tive frozen sections were determined.

Results. The sensitivities of scintigraphy and ultrasonogra-

phy were 62% and 55%, and the specificity was 95% for both

procedures. The sensitivity of combined techniques was 73%.

The scintigraphy detected 7/9 (78%) ectopic PTGs, whereas

ultrasonography was always negative. A PTG maximum longi-

tudinal diameter <8 mm, the presence of diffuse hyperplasia,

the upper localization of glands, and the presence of concomi-

tant thyroid disease reduced the sensitivity and specificity of

imaging techniques. In cases of positive imaging, the rate of

intraoperative frozen sections was significantly lower.

Conclusions. The ultrasonography and sestamibi scintigra-

phy, which showed a higher sensitivity than that of either ultra-

sonography or scintigraphy alone, led to a reduction of

intraoperative frozen sections and to preoperative diagnosis of

ectopic (29%) or supernumerary PTGs (10%) and concomitant

nodular thyroid disease (24%). VVC 2010 Wiley Periodicals,

Inc. Head Neck 32: 1226–1235, 2010

Keywords: secondary hyperparathyroidism; parathyroid glands;

echography; scintigraphy; hemodialysis

Secondary hyperparathyroidism (SHPT) is asevere disease of patients who undergo hemo-dialysis, causing substantial morbidity and mor-tality consequent to progressive osteodystrophyand vascular and soft tissue calcification.1–4

Although underlying mechanisms of SHPT arenot completely known, it seems evident that theinitial stimuli (hypocalcemia, hyerphosphate-mia, and low calcitriol concentrations), whichcause parathyroid-cell hypertrophy, with timedetermine initially diffuse and reversible and

Correspondence to: C. Vulpio

VVC 2010 Wiley Periodicals, Inc.

1226 Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010

successively nodular and irreversible hyperpla-sia of parathyroid glands (PTGs).5

When nodular hyperplasia develops, themedical therapy may ultimately fail to controlSHPT and may expose the patients to an unac-ceptable risk of vascular and soft tissue calcifi-cations.6,7 At this point of SHPT evolution,surgery may be indicated. However, surgicalresults for uremic SHPT are less satisfactorythan those in primary hyperparathyroidism(PHPT), the rates of persistent and recurrentdisease being higher and ranging between 10%and 30%.8 The principal cause of surgical failurestill remains the incomplete intraoperative iden-tification of all PTGs.9

Although the use of preoperative localizationstudies and intraoperative intact parathyroidhormone (iPTH) for the management of PHPTcertainly improves the surgical outcome andfacilitates the development of minimal invasiveapproach, it is still an argument of debate whichis the best diagnostic tool to preoperativelylocalize PTG in SHPT: high-resolution ultraso-nography, technetium-99m (99mTc) sestamibi(known as methoxyisobutylisonitrile or MIBI)scintigraphy, intraoperative gamma probe, orintraoperative quick iPTH assay.10,11 Neverthe-less, few surgeons actually believe that preoper-ative imaging techniques can improve thesuccess rate of first surgery in uremic SHPT.12

Indeed, studies on the role of 99mTc sestamibiin SHPT have led to conflicting results13–27; like-wise for studies that have combined ultrasonog-raphy and sestamibi scintigraphy.28–32

The present study aimed at assessing thesensitivity and specificity of the combination ofhigh-resolution ultrasonography and 99mTc ses-tamibi dual-phase scintigraphy in the preopera-tive localization of PTG as well as at evaluatingtheir usefulness in surgical decision-making inhemodialysis patients with SHPT referred forfirst parathyroid surgery.

PATIENTS AND METHODS

Between January 2001 and June 2007, at theDialysis Unit of the Department of Surgery ofthe Catholic University of Rome, 21 patients (8men, 13 women) with consecutive end-stage re-nal disease on maintenance bicarbonate hemo-dialysis were scheduled for parathyroid surgeryfor refractory SHPT. The mean age was 46 � 18years and the mean dialytic age was 7 � 4

years. All patients underwent preoperativeimaging studies (ultasonography and sestamibiscintigraphy) and parathyroidectomy (PTX).

The study was approved by the local ethicscommittee, and written informed consent wasobtained from all patients before diagnostic ex-amination and parathyroidectomy.

Scintigraphy. The anteroposterior full views ofthe neck and thorax and magnified views of theneck were acquired with a gamma camera (e-CAM, Siemens Medical Solutions USA, BuffaloGrove, IL) with the patient in the supine posi-tion at 10 (thyroid phase) and 120 minutes(parathyroid phase) after intravenous adminis-tration of 370 megabecquerels (MBq) (10 milli-curie [mCi]) of MIBI. The images were obtainedover 15 minutes using a pinhole collimator (ma-trix size: 128 � 128; zoom: 2.0), whereas thethorax images were obtained with a parallel-hole, low-energy, high-resolution collimator (ma-trix size: 256 � 256; zoom: 1.0). At 140 minutes,all patients underwent a thyroid scan to ruleout the presence of thyroid nodules and to aidin the interpretation of parathyroid images.Gamma camera settings where identical toMIBI neck scintigraphy, and the 99mTc-pertech-netate dose was 148 MBq (4 mCi). Two special-ists blind to ultrasonography, clinical, andbiochemical findings, interpreted the scans anddefined the PTG number and site in relation tothyroid lobes. The MIBI scan was consideredpositive for PTG when there was a focal area ofincreased uptake in the thyroid phase, showinga relative increase over time and not detectablein thyroid scintigraphy.

The scintigraphy finding for each gland wasdefined as true positive, false positive, true neg-ative, or false negative on the basis of the pa-thology results.

Ultrasonography. Ultrasonography was per-formed by a skilled radiologist blind to the MIBIresults, clinical data, and iPTH levels. The sameultrasound device and setting (Toshiba Aplio;Toshiba Co. Ltd., Tokyo, Japan) connected to amultifrequency high-resolution probe was usedin all patients. Usually, normal PTGs are notvisible at ultrasound. Enlarged glands usuallyappear as an oval, hypoechoic nodule, locatedclose to the thyroid gland, but clearly separatedby a well-defined echogenic line that representsthe capsule. The PTG size was defined as themaximal longitudinal diameter (MLD) of the

Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010 1227

gland, as previously described.33 Ultrasonogra-phy finding for each gland was defined as truepositive, false positive, true negative, or falsenegative on the basis of the pathology results.

Surgical Procedures. Subtotal PTX (sPTX) ortotal PTX (tPTX) with implant was performedin young patients or in candidates for kidneytransplantation, whereas older patients under-went tPTX without autotransplant. All patientsunderwent bilateral transcervical thymectomy.Results of imaging techniques were used by thesurgeon at the time of surgery. All surgical pro-cedures were performed by the same surgeon(M.C.). Intraoperative histological analysis onfrozen sections was performed only whendeemed necessary by the surgeon.

The sPTX included the ablation of 3 glandsand half of the fourth gland. Half of the glandwith the most normal appearance or with an ana-tomical position that would have not complicatedreintervention in the case of recurrence was leftin site and marked with a nonresorbable threador metallic clip to facilitate further detection. Thechoice of the gland with the lowest chance of re-currence was based on criteria of size, vasculari-zation, appearance at surgical gross examination(homogeneous or nodular hyperplasia), and,when possible, absent MIBI uptake. To evaluatethe results of surgery, we adopted the criteriasuggested by Tominaga et al6 as follows: whenthe lowest PTH value exceeds the upper normalrange (60 pg/mL), we considered that the patienthad persistent SHPT, which means that a glandor glands have possibly been left behind. WhenPTH decreased to a value under 60 pg/mL and

then reincreased, we were dealing with recurrentSHPT. The mean follow-up was 30.6 � 18 months(means � SD; range, 6–60).

Histology. In all, 78 PTGs belonging to 21patients were removed.

The surgical specimens were fixed in 10%buffered formaldehyde, embedded in paraffinand the 5-lm-thick sections, and were stainedwith hematoxylin-eosin for the histological ex-amination. Three histologic parameters were an-alyzed for this study: confirmation of thepresence of parathyroid tissue during the intrao-perative frozen section examination and bothsize and type of glandular hyperplasia of theremoved PTGs. In accord with Tominaga,1 thePTG hyperplasia was classified as follows: dif-fuse hyperplasia, early nodularity, macronodularhyperplasia, or single nodular gland hyperplasia(adenoma like hyperplasia).

When a concurrent thyroidectomy was carriedout, the histological examination was performedwith the same procedure as that for the PTGs.

Statistical Analysis. GraphPad Prism (version4.0 2003) for Microsoft Windows XP (Microsoft,Redmond, WA) was used for data analysis.

Continuous variables are expressed as mean� SD and categorical variables as frequencies.The appropriate test (t test, analysis of variance[ANOVA], Student–Newman–Keuls post hoccomparison, chi-square test) was used whencomparing groups’ means or frequencies.

Linear correlation was evaluated by Pear-son’s test or Spearman’ test. Values of p < .05were considered statistically significant.

FIGURE 1. Technetium-99m (99mTc) sestamibi (known as methoxyisobutylisonitrile or MIBI) scintigraphy: early and delayed anterior

views of the neck are shown in A and B, respectively. 99mTc-pertechnetate thyroid scintigraphy is shown in C. Scintigraphy detected

an intrathyroidal parathyroid gland (PTG) as an abnormal ‘‘hot spot’’ in the 99mTC-sestamibi delayed image (B). The parathyroid rather

than thyroid origin of the scintigraphic finding is demonstrated by the absence of 99mTc- pertechnetate uptake in C.

1228 Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010

RESULTS

Surgical Outcome. Assuming that 4 PTGs arepresent in each patient, the hypothetical totalnumber of PTGs in the 21 patients would havebeen 82 PTGs (1 patient had a previous hemi-thyroidectomy). In all, 78 PTGs (95%) wereidentified and surgically removed.

Fourteen of 21 patients showed 4 PTGs, 2patients showed 5 PTGs (10%) (1 supernumeraryretroesophageal ectopic glands, 1 intrathyroid), 3patients showed 3 PTGs, and 2 patients showed 2PTGs (1 patient had previously undergonehemithyroidectomy).

In accord with the surgeon’s report, 69 PTGswere found in typical sites (33 glands weresuperior, 36 inferior) and 9 PTGs (12%) in atypi-cal localizations: 1 intrathyroid (see Figure 1), 1

in the upper superior mediastinum, 2 in the leftcervical paratracheal space, 1 in the right cervi-cal paratracheal space, 2 in the left thymus, 1behind the right carotid–upper esophagealgroove (see Figure 2), and 1 in the left retro-esophageal space (Figure 3).

The 9 atypical PTGs were found in 6 of 21patients (29%).

At pathologic examination, 15 PTGs (19%)showed diffuse hyperplasia and 63PTGs (81%)nod-ular hyperplasia. Table 1 shows the number ofPTGs detected and removed, surgical procedure,follow-up, and outcome for each patient.

Eleven of 21 patients (53%) included in thestudy had concomitant echographic thyroid abnor-malities, and 5 patients (24%) had a multinodulargoiter (MNG) (4 nontoxic MNGs and 1 toxic MNG).Overall, 5 total thyroidectomies were performed.

FIGURE 2. The right superior and right inferior PTGs were detected in a typical anatomic site; a supernumerary ectopic right superior

PTG was detected in the upper pharyngeal-esophageal-carotid groove. The 99mTc-sestamibi scintigraphy revealed 5 PTGs. T, thyroid;

RS, right superior PTG; RI, right inferior PTG; P, pharynx; C, carotid. Arrow: ectopic supernumerary superior PTG. [Color figure can

be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010 1229

In 4 of 5 patients, a papillary carcinoma wasdetected (1 pT3 multifocal papillary carcinoma, 1clear cell papillary carcinoma with a diameter of0.9 cm, 1 microfocal papillary carcinoma with adiameter of 0.1 cm, 1 multinodular and bilateralsubcentimetral papillary carcinoma). One infil-trating papillary carcinoma was suspected onpreoperative ultrasonography; another case wasdetected during surgical exploration. In these 2cases, a central compartment lymphectomy was

performed. The remaining 2 cases were inciden-tally identified at definitive histology.

One case of persistent SHPT (5%) wasobserved as well as 2 cases of relapse of SHPT(9%). No deaths or major postoperative compli-cations were observed.

Imaging Findings. Ultrasonography detected 43of the 78 PTGs that were removed surgically. Sim-ilarly, scintigraphy detected 49 of 78 PTGs. Asshown in Table 2, of the 43 PTGs detected byultrasound, 8 were not detected by scintigraphy.Of the 49 PTGs detected by scintigraphy, 14 werenot detected by ultrasound. In all, 57 PTGs weredetected by ultrasonography or scintigraphy.

Sestamibi scintiscans had a sensitivity andspecificity of 62% and 95%, and ultrasonographyof 55% and 95%, respectively. The differenceswere not statistically significant. The associationof ultrasonography and scintigraphy had a sen-sitivity and specificity of 73% and 91%,respectively.

The PTG size and the PTG diameter detectedon ultrasound and on pathologic examinationwere significantly correlated (r ¼ .596; p <.0001, 95% confidence interval [CI] 0.4286 to0.7245). As expected, the mean histologicalMLD of PTG visualized by ultrasonography andscintigraphy was higher than that of missedones (Table 3).

The scintigraphy was positive in 25% of PTGwith diffuse hyperplasia, in 62% of PTGs withearly micronodular hyperplasia, and in 100% ofcases of adenoma-like hyperplasia (chi-squaretest, p < .005) (see Figure 4) The mean � SDultrasound MLD of PTGs with diffuse or nodu-lar hyperplasia was 7.1 � 0.92 and 12.10 �0.66, respectively (p < .001).

Table 4 shows that, despite a similar MLD,the percentage of PTGs visualized by ultraso-nography and scintigraphy was higher for infe-rior PTGs than for superior ones. For PTGslocalized in atypical sites, ultrasonography wasalways negative, whereas scintigraphy was posi-tive in 7/9 (78%) of cases.

The sonography and scintigraphy sensitiv-ities were similar in patients with and withoutconcomitant thyroid diseases. Conversely, ultra-sonography and scintigraphy specificities werelower in patients with concomitant thyroid dis-ease. The scintigraphy was falsely positive in 1patient (5%) with a voluminous oxyphil ade-noma in multinodular goiter.

FIGURE 3. The left superior PTG was not detected by ultra-

sound (B) but it was evident at scintigraphy (A). The surgeon

found the PTG behind the upper esophagus (C), in a site that

corresponded to the scintigraphic uptake. Tia, thyroid inferior ar-

tery; T, left thyroid lobe; P-E, pharynx-upper esophagus; PTG,

superior left parathyroid gland. [Color figure can be viewed in

the online issue, which is available at wileyonlinelibrary.com.]

1230 Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010

Three intraoperative frozen sections wereperformed when the ultrasonography and scin-tigraphy were positive, whereas 20 frozen sec-tions were performed when ultrasonographyand scintigraphy were negative (p < .0001).Likewise, frozen sections were more frequentlyperformed when the PTGs were located in atypi-cal rather than in typical sites.

DISCUSSION

The present study shows that the combinationof ultrasonography and 99mTC sestamibi scin-tigraphy for the preoperative localization ofparathyroid glands in SHPT has a higher sensi-tivity than ultrasonography or sestamibi scintig-raphy alone. Furthermore, the combination ofthese imaging techniques is particularly usefuland complementary in the planning of the surgi-cal strategy of uremic SHPT—if we consider thefrequency of patients with concomitant thyroiddiseases (24%), ectopic (29%), and supernumer-ary glands (10%).

These data are in accord with recent reportsin which the sensitivity of the combination ofthe 2 imaging techniques proved to be signifi-cantly better than that of the single proce-dures.28–32 It is useful to be reminded that the

operators of each of the imaging techniqueswere blind to the results of the other exam.Thus, it is possible that the sensitivity and spec-ificity are underestimated. Taking into accountthese considerations, we propose to perform firstthe less operator-dependent scintigraphy, andthereafter the ultrasonography. In this way, theradiologist may be easily guided to areas withsuspicious parathyroid tissue.

However, it seems difficult to localize allPTGs by ultrasonography and scintigraphy inSHPT because PTG hyperplasia is an asynchro-nous and asymmetrical process.

As previously reported,34–40 the PTG site(superior or inferior, typical or ectopic), the

Table 1. Number of PTGs detected and removed in each patient by PTX and outcome.

Patient

PTGs

PTX

Thyroid

resection Thyroid disease Follow-up ResultsDetected Removed

1 2 2 ST 18 Persistence

2 2 2 T Hemi Hishimoto thyroiditis 44 Effective

3 3 3 T Total MNG microfocal papillary Ca. 15 Effective

4 3 3 T 60 Effective

5 4 3 ST 48 Effective

6 4 3 and 1/2 ST Total MNG 12 Effective

7 4 3 and 1/2 ST 45 Effective

8 4 3 and 1/2 ST 60 Effective

9 4 3 and 1/2 ST 38 Effective

10 4 3 and 1/2 ST Total MNG papillary Ca. 20 Effective

11 4 4 T 20 Effective

12 4 4 T 12 Effective

13 4 4 T 54 Effective

14 4 4 T 13 Effective

15 4 4 T Total MNG oxyphil adenoma þmicrofocal papillary Ca.

15 Effective

16 4 4 T Total MNG papillary Ca. pT3m 12 Effective

17 4 4 T þ A 48 Effective

18 5 5 T 21 Effective

19 5 5 T 30 Effective

20 4 4 T 6 Effective

21 3 3 T 6 Relapse

Abbreviations: PTG, parathyroid gland; PTX, parathyroidectomy: ST, subtotal 7/8; T, total; T þ A, total plus autotransplant; MNG, multinodular goiter;Ca., carcinoma; pT3, multifocal papillary carcinoma.

Table 2. Number of PTGs individually detected by

ultrasonography and scintigraphy.

Ultrasound findings

No. by scintigraphy

TotalPositive Negative

Positive 35 8 43

Negative 14 21 35

Total 49 29 78

Abbreviation: PTG, parathyroid gland.Note: When positives are considered together, findings of both sonog-raphy and scintigraphy allowed us to detect 57 PTGs (73%); p <.0001.

Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010 1231

diameter, and the type of hyperplasia are themain factors determining the ultrasonographypatterns and scintigraphy uptake. With regardto the site, the present study confirms that, de-spite a similar MLD, the percentage of PTGsvisualized by ultrasonography and scintigraphywas higher for inferior than that for superiorPTG. Possibly, the superior PTGs are usuallylocalized at the level of the thyrolaryngealgroove, a site explorable by ultrasonographyonly with some difficulty. In addition, superiorPTGs are just behind thyroid lobes and closed tothe thick thyroid tissue. This makes identifica-tion by scintigraphy difficult.

With regard to the type of hyperplasia, theMIBI sensitivity was 67% and 100% for micro-nodular and macronodular hyperplasia, respec-tively, and 25% for diffuse hyperplasia. Thesedata agree with those of Nishida et al,41 whorecently reported 28% of positive scintigraphy indiffuse hyperplasia. Accordingly, it has beenshown that the number of the mitosis and cellproliferation, of the oxyphil cells and mitochon-dria prevailing in the advanced forms of PTGhyperplasia facilitates the cellular sestamibiuptake.36 As suggested by Fuster et al,22 the dif-ferent MIBI uptake in diffuse or nodular hyper-plasia could provide a useful element foridentification and surgical evaluation of thePTG to partially spare in case of subtotalparathyroidectomy.

Finally, in accord with other reports, wefound that the PTG diameter is a very impor-tant predictive factor of nodular hyperplasia

and MIBI uptake. We have observed that PTGwith MLD < 8 mm and absent MIBI uptakeusually showed diffuse hyperplasia. The encour-aging surgical outcome of this series is possiblyexplained by the fact that PTG with a diameter>10 mm or with positive MIBI uptake werenever left in site or reimplanted.

Another finding of the present study is thatin the localization of ectopic PTG, the scintigra-phy sensitivity is very high, whereas the ultra-sonography sensitivity is null. Ultrasonographyalways failed to detect PTG localized in atypicalsites, whereas scintigraphy was positive in 78%of cases, although the mean MLD of PTG was7.8 � 2.2 mm. Thus, scintigraphy is the onlyimaging technique that can identify ectopicglands in SHPT.34

More recently, the use of single-photon emis-sion CT (SPECT) or SPECT/CT has been recom-mended to better define the position of anectopic focus. The data are yet limited. However,the 2009 European Association of Nuclear Medi-cine (EANM) guidelines42 suggest that althoughSPECT and SPECT/CT imaging are becomingvery helpful, they cannot replace the standardplanar and ‘‘pinhole’’ protocols that are stillessential for optimal resolution in the thyroidbed region and for a correct diagnosis.

Patients with SHPT have been found to havea higher rate of ectopic and or supernumeraryPTG (20% to 43%) than those with primarydisease (6% to 18%).9,43–47 However, it should bestated that there are particularly insidiousectopic glands that some authors define ‘‘majorectopy.’’ As suggested by Mariani et al48 theterm ‘‘major ectopy’’ refers to PTG located inthe mediastinum, or high in the neck, or lateralto the cervical neurovascular bundle, or insidethe thyroid gland. This justifies the need for

Table 3. MLD (mean � SD) of PTGs detected at pathology in

accord with ultrasonography and scintigraphy findings.

Modality MLD, mean � SD, mm p value

Typical site

Ultrasonography .004

þ 12.7 � 0.7

– 9.3 � 0.8

Scintigraphy .002

þ 13.0 � 0.7*

– 9.4 � 0.8

Ectopic site

Ultrasonography

þ —

– —

Scintigraphy .03*

þ 8.3 � 2.2*

– 4

Abbreviations: MLD, maximum longitudinal diameter; PTG, parathyroidgland.*t test, p < .03.

FIGURE 4. 99mTc sestamibi uptake in PTG with diffuse hyper-

plasia (25%) or nodular hyperplasia (85%).

1232 Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010

additional diagnostic techniques for surgical ex-ploration. These ectopic PTGs are those thatmost easily can be left in situ in the firstinstance, since the routine technique of surgicalexploration does not expose these regions nordoes it usually include thyroidectomy. In thepresent study, 3 major ectopic glands (1 intra-thyroid and 2 retrofaringealesophageal) werefound that would have been hardly removed inthe absence of scintigraphic imaging.

Moreover, in 2 patients (10%) supernumeraryPTGs were found, confirming the reported dataabout the increased frequency of supernumeraryPTGs in uremic SHPT (13% to 20%) comparedwith normal subjects (5% to 13%).43–47 Based onall these considerations, we suggest the routineuse of ultrasound and sestamibi scans prior tosurgical exploration in SHPT.

These procedures may be associated with theintraoperative parathyroid hormone (io-PTH)assay. It is well known that the io-PTH assayhas been proposed to assess the adequacy of sur-gery and to detect supernumerary glands. Obvi-ously, the io-PTH assay is not able to indicatethe site of supernumerary glands eventuallypresent.

Interestingly, in the present study we docu-mented a reduction of the number of frozen sec-tions performed during surgery when bothultrasonography and scintigraphy were positive,with a consequent decrease of operative timeand economical costs. Estimated cost reductionfor each omitted frozen section was 100 euros inour institution. The frozen sections were signifi-cantly more frequent in cases of ectopic PTG ornegative imaging. Similarly, Chan et al49

reported that in 42 patients with negative imag-ing a mean of 4 (range, 1–11) frozen sections perpatient were sent for pathologic examination.

To ensure the removal of all PTGs, Tominagaet al6 recommend the histological confirmationduring surgery in all cases. Of note, in the pres-ent study, when ultrasonography and scintigra-phy were both positive, histological examinationwas always positive for PTG, suggesting that inthese cases the frozen sections may be avoided.

Finally, the utility to perform both ultraso-nography and scintigraphy preoperatively inpatients with SHPT who are candidates for sur-gery comes from the observation of concomitantnodular thyroid disease in 24% of patientsincluded in the present study. The frequency ofassociation of thyroid nodular disease or carci-noma with SHPT ranges between 3% and37%.50–52 Such association is considered casualand similar to that of the general popula-tion.15,53,54 However, it is well known that thedetection of abnormal PTGs by both ultrasonog-raphy and scintigraphy may be impaired in thepresence of nodular28,55,56 or multinodular thy-roid disease.16,39 Indeed, we did not find signifi-cant differences in the sensitivity ofultrasonography and scintigraphy betweenSHPT with and without concomitant thyroid dis-ease. Conversely, the specificity of both methodswas 100% in SHPT without thyroid disease and80% in SHPT with thyroid diseases. The highprevalence of concomitant nodular thyroid dis-ease in SHPT further supports the usefulness ofpreoperative ultrasound in the correct assess-ment of parathyroid and thyroid status inpatients with SHPT45 and the adjunct of thyroidscintigraphic imaging to the standard dual-phase parathyroid scan (as today routineworkup in several European countries with io-dine-deficient areas).

In conclusion, the present study shows thatthe combined use of ultrasound and MIBI

Table 4. Number of superior and inferior PTGs detected by ultrasonography, scintigraphy, and histology in typical and ectopic

localizations.

Modality

Typical PTGs

Ectopic PTGs, no. (%) p valueSuperior, no. (%) Inferior, no. (%) Total

Ultrasonography .02

þ 14 (42) 29 (81) 43 0 (0)

– 19 7 9

Scintigraphy .03

þ 16 (49) 26 (72) 42 7 (78)

– 17 10 2

Histology 33 (100) 36 (100) 69 9 (100)

MLD at pathology 10.5 � 4.6 12.4 � 4.6 11.5 � 4.7 8.3 � 2.2 ns

Abbreviations: PTG, parathyroid gland; MLD, maximum longitudinal diameter; ns, not significant.

Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September 2010 1233

scintigraphy in the preoperative evaluation ofend-stage renal disease patients with SHPT hasan higher sensitivity and leads to detection ofthe ectopic and supernumerary PTG and con-comitant thyroid disease, and to a significantreduction of the number of intraoperative frozensections for histology.

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