Usefulness of the combination of ultrasonography and 99mTc-sestamibi scintigraphy in the preoperative evaluation of uremic secondary hyperparathyroidism.
ABSTRACT The usefulness of the combination of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) parathyroid scintigraphy and ultrasonography to detect parathyroid glands (PTGs) in secondary hyperparathyroidism (SHPT) is still controversial.
In all, 21 patients with SHPT underwent parathyroidectomy. The sensitivity and specificity of ultrasonography and scintigraphy related to site, size, hyperplasia type of PTG, concomitant thyroid disease, and the frequency of intraoperative frozen sections were determined.
The sensitivities of scintigraphy and ultrasonography 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 longitudinal diameter <8 mm, the presence of diffuse hyperplasia, the upper localization of glands, and the presence of concomitant thyroid disease reduced the sensitivity and specificity of imaging techniques. In cases of positive imaging, the rate of intraoperative frozen sections was significantly lower.
The ultrasonography and sestamibi scintigraphy, which showed a higher sensitivity than that of either ultrasonography 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%).
Article: Histopathology and pathophysiology of secondary hyperparathyroidism due to chronic renal failure.[show abstract] [hide abstract]
ABSTRACT: Between 1973 and 1992, 300 patients underwent parathyroidectomy for secondary hyperparathyroidism due to chronic renal failure in our departments. Using parathyroid glands obtained at operation, histopathological studies were performed, and to estimate pathophysiology DNA analysis of parathyroid cell nuclei and calcium-regulated parathyroid hormone (PTH) secretion in vitro were estimated. PTH mRNA expression was evaluated by in situ hybridization. The typical histopathological findings were asymmetric enlargement, nodularities and increased number of oxyphil cells. Secondary hyperplasia was divided into 2 types: diffuse and nodular type hyperplasia. In the histopathological study nodular hyperplasia indicated more aggressive proliferation. In DNA analysis the relative number of scattered cells in the DNA synthesis phase was significantly greater in nodular than in diffuse hyperplasia. The half of the maximal inhibition of PTH secretion for calcium (the set-point) in the cells from nodular hyperplasia was higher than in the cells obtained from diffuse hyperplasia. However, there was no difference in expression of PTH mRNA in nodular and diffuse hyperplasia. These data suggested that nodular hyperplasia was more progressively hyperplastic, had more aggressive proliferative activities and showed more abnormal regulation of PTH secretion. These results imply that to prevent graft-dependent recurrent hyperparathyroidism after parathyroidectomy, the nodular hyperplastic tissue should not be autografted.Clinical nephrology 12/1995; 44 Suppl 1:S42-7. · 1.17 Impact Factor
Article: Histopathology, pathophysiology, and indications for surgical treatment of renal hyperparathyroidism.[show abstract] [hide abstract]
ABSTRACT: Morphological changes in the parathyroid glands evidently occur early during renal failure. Histopathological investigations have suggested that parathyroid cells initially increase diffusely with a normal lobular structure (diffuse hyperplasia). The parathyroid glands then become hyperplastic with some nodules (nodular hyperplasia). Cells in nodules grow monoclonally and proliferate aggressively, possibly induced by some kind of genetic abnormality. Pathophysiologically, in cells consisting of hyperplastic nodules, suppression of parathyroid hormone (PTH) secretion under the influence of excess extracellular calcium is more deranged, possibly due to a reduction of calcium-sensing receptors. Vitamin D receptor density decreases more severely in these cells, possibly causing abnormal PTH synthesis, PTH secretion, and even parathyroid cell proliferation. According to histopathological and pathophysiological findings, patients with nodular hyperplasia during renal hyperparathyroidism may be refractory to medical treatments, including calcitriol pulse therapy, and parathyroidectomy will become necessary. There is a relationship between the pattern of parathyroid hyperplasia and glandular weight in which glands weighing more than 500 mg may be pathognomonic of nodular hyperplasia. Glandular volume, estimated by ultrasonography, is one of several important criteria indicating parathyroidectomy. In order to prevent a recurrence of hyperparathyroidism, all nodular hyperplastic tissue should be extirpated.Seminars in Surgical Oncology 13(2):78-86.
[show abstract] [hide abstract]
ABSTRACT: Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and an important cause of morbidity, decreased quality of life, and extraskeletal calcification that have been associated with increased cardiovascular mortality. These disturbances have traditionally been termed renal osteodystrophy and classified on the basis of bone biopsy. Kidney Disease: Improving Global Outcomes (KDIGO) recently sponsored a Controversies Conference to evaluate this definition. The recommendations were that (1) the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD and (2) the term CKD-mineral and bone disorder (CKD-MBD) be used to describe the broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is manifested by an abnormality of any one or a combination of the following: laboratory-abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; bone-changes in bone turnover, mineralization, volume, linear growth, or strength; and calcification-vascular or other soft-tissue calcification. The pathogenesis and clinical manifestations of these components of CKD-MBD are described in detail in this issue of Advances in Chronic Kidney Disease.Advances in Chronic Kidney Disease 02/2007; 14(1):3-12. · 3.01 Impact Factor
USEFULNESS OF THE COMBINATION OF
ULTRASONOGRAPHYAND 99MTC-SESTAMIBI SCINTIGRAPHY
IN THE PREOPERATIVE EVALUATION OF UREMIC
Carlo Vulpio, MD,1Maurizio Bossola, MD,1Annamaria De Gaetano, MD,2Giulia Maresca, MD,2
Isabella Bruno, MD,3Guido Fadda, MD,4Francesca Morassi, MD,4Sabina C. Magalini, MD,1
Alessandro Giordano, MD,3Marco Castagneto, MD1
1Istituto Clinica Chirurgica, Universita ` Cattolica del Sacro Cuore, Rome, Italy. E-mail: email@example.com
2Istituto di Radiologia, Universita ` Cattolica del Sacro Cuore, Rome, Italy
3Istituto di Medicina Nucleare, Universita ` Cattolica del Sacro Cuore, Rome, Italy
4Istituto di Anatomia Patologica, Universita ` Cattolica del Sacro Cuore, Rome, Italy
Accepted 20 October 2009
Published online 20 January 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/hed.21320
parathyroid scintigraphy and ultrasonography to detect para-
thyroid glands (PTGs) insecondary
(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.
Background. The usefulness of the combination
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%).
Inc. Head Neck 32: 1226–1235, 2010
C 2010 Wiley Periodicals,
Keywords: secondary hyperparathyroidism; parathyroid glands;
echography; scintigraphy; hemodialysis
Secondary hyperparathyroidism (SHPT) is a
severe disease of patients who undergo hemo-
dialysis, causing substantial morbidity and mor-
tality consequent to progressive osteodystrophy
and vascular and soft tissue calcification.1–4
Although underlying mechanisms of SHPT are
not completely known, it seems evident that the
initial stimuli (hypocalcemia, hyerphosphate-
mia, and low calcitriol concentrations), which
cause parathyroid-cell hypertrophy, with time
determine initially diffuse and reversible and
Correspondence to: C. Vulpio
C 2010 Wiley Periodicals, Inc.
1226 Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September2010
successively nodular and irreversible hyperpla-
sia of parathyroid glands (PTGs).5
medical therapy may ultimately fail to control
SHPT and may expose the patients to an unac-
ceptable risk of vascular and soft tissue calcifi-
At this point of SHPT evolution,
surgery may be indicated. However, surgical
results for uremic SHPT are less satisfactory
(PHPT), the rates of persistent and recurrent
disease being higher and ranging between 10%
and 30%.8The principal cause of surgical failure
still remains the incomplete intraoperative iden-
tification of all PTGs.9
Although the use of preoperative localization
studies and intraoperative intact parathyroid
hormone (iPTH) for the management of PHPT
certainly improves the surgical outcome and
facilitates the development of minimal invasive
approach, it is still an argument of debate which
is the best diagnostic tool to preoperatively
localize PTG in SHPT: high-resolution ultraso-
nography, technetium-99m (99mTc) sestamibi
(known as methoxyisobutylisonitrile or MIBI)
scintigraphy, intraoperative gamma probe, or
intraoperative quick iPTH assay.10,11Neverthe-
less, few surgeons actually believe that preoper-
success rate of first surgery in uremic SHPT.12
Indeed, studies on the role of 99mTc sestamibi
in 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 the
sensitivity and specificity of the combination of
high-resolution ultrasonography and 99mTc ses-
tamibi dual-phase scintigraphy in the preopera-
tive localization of PTG as well as at evaluating
their usefulness in surgical decision-making in
hemodialysis patients with SHPT referred for
first parathyroid surgery.
PATIENTS AND METHODS
Between January 2001 and June 2007, at the
Dialysis Unit of the Department of Surgery of
the Catholic University of Rome, 21 patients (8
men, 13 women) with consecutive end-stage re-
nal disease on maintenance bicarbonate hemo-
dialysis were scheduled for parathyroid surgery
for refractory SHPT. The mean age was 46 ? 18
years and the mean dialytic age was 7 ? 4
imaging studies (ultasonography and sestamibi
scintigraphy) and parathyroidectomy (PTX).
The study was approved by the local ethics
committee, and written informed consent was
obtained from all patients before diagnostic ex-
amination and parathyroidectomy.
All patients underwent preoperative
the neck and thorax and magnified views of the
neck were acquired with a gamma camera (e-
CAM, Siemens Medical Solutions USA, Buffalo
Grove, 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 obtained
over 15 minutes using a pinhole collimator (ma-
trix size: 128 ? 128; zoom: 2.0), whereas the
thorax 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 rule
out the presence of thyroid nodules and to aid
in the interpretation of parathyroid images.
Gamma camera settings where identical to
MIBI neck scintigraphy, and the 99mTc-pertech-
netate dose was 148 MBq (4 mCi). Two special-
ists blind toultrasonography,
biochemical findings, interpreted the scans and
defined the PTG number and site in relation to
thyroid lobes. The MIBI scan was considered
positive for PTG when there was a focal area of
increased uptake in the thyroid phase, showing
a relative increase over time and not detectable
in thyroid scintigraphy.
The scintigraphy finding for each gland was
defined as true positive, false positive, true neg-
ative, or false negative on the basis of the pa-
The anteroposterior full views of
formed by a skilled radiologist blind to the MIBI
results, clinical data, and iPTH levels. The same
ultrasound device and setting (Toshiba Aplio;
Toshiba Co. Ltd., Tokyo, Japan) connected to a
multifrequency high-resolution probe was used
in all patients. Usually, normal PTGs are not
visible at ultrasound. Enlarged glands usually
appear as an oval, hypoechoic nodule, located
close to the thyroid gland, but clearly separated
by a well-defined echogenic line that represents
the capsule. The PTG size was defined as the
maximal longitudinal diameter (MLD) of the
Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hedSeptember20101227
gland, as previously described.33Ultrasonogra-
phy finding for each gland was defined as true
positive, false positive, true negative, or false
negative on the basis of the pathology results.
total PTX (tPTX) with implant was performed
in young patients or in candidates for kidney
transplantation, whereas older patients under-
went tPTX without autotransplant. All patients
underwent bilateral transcervical thymectomy.
Results of imaging techniques were used by the
surgeon at the time of surgery. All surgical pro-
cedures were performed by the same surgeon
(M.C.). Intraoperative histological analysis on
deemed necessary by the surgeon.
The sPTX included the ablation of 3 glands
and half of the fourth gland. Half of the gland
with the most normal appearance or with an ana-
tomical position that would have not complicated
reintervention in the case of recurrence was left
in site and marked with a nonresorbable thread
or metallic clip to facilitate further detection. The
choice 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
when possible, absent MIBI uptake. To evaluate
the results of surgery, we adopted the criteria
suggested by Tominaga et al6as follows: when
the lowest PTH value exceeds the upper normal
range (60 pg/mL), we considered that the patient
had persistent SHPT, which means that a gland
or glands have possibly been left behind. When
PTH decreased to a value under 60 pg/mL and
Subtotal PTX (sPTX) or
then reincreased, we were dealing with recurrent
SHPT. The mean follow-up was 30.6 ? 18 months
(means ? SD; range, 6–60).
patients were removed.
The surgical specimens were fixed in 10%
buffered formaldehyde, embedded in paraffin
and the 5-lm-thick sections, and were stained
with hematoxylin-eosin for the histological ex-
amination. Three histologic parameters were an-
presence of parathyroid tissue during the intrao-
perative frozen section examination and both
size and type of glandular hyperplasia of the
removed PTGs. In accord with Tominaga,1the
PTG hyperplasia was classified as follows: dif-
fuse hyperplasia, early nodularity, macronodular
hyperplasia, or single nodular gland hyperplasia
(adenoma like hyperplasia).
When a concurrent thyroidectomy was carried
out, the histological examination was performed
with the same procedure as that for the PTGs.
In all, 78 PTGs belonging to 21
4.0 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
comparison, chi-square test) was used when
comparing groups’ means or frequencies.
Linear correlation was evaluated by Pear-
son’s test or Spearman’ test. Values of p < .05
were considered statistically significant.
GraphPad Prism (version
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.
1228Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hedSeptember2010
present in each patient, the hypothetical total
number of PTGs in the 21 patients would have
been 82 PTGs (1 patient had a previous hemi-
thyroidectomy). In all, 78 PTGs (95%) were
identified and surgically removed.
Fourteen of 21 patients showed 4 PTGs, 2
patients showed 5 PTGs (10%) (1 supernumerary
retroesophageal ectopic glands, 1 intrathyroid), 3
patients showed 3 PTGs, and 2 patients showed 2
PTGs (1 patienthad
In accord with the surgeon’s report, 69 PTGs
were found in typical sites (33 glands were
superior, 36 inferior) and 9 PTGs (12%) in atypi-
cal localizations: 1 intrathyroid (see Figure 1), 1
Assuming that 4 PTGs are
in the upper superior mediastinum, 2 in the left
cervical paratracheal space, 1 in the right cervi-
cal paratracheal space, 2 in the left thymus, 1
groove (see Figure 2), and 1 in the left retro-
esophageal space (Figure 3).
The 9 atypical PTGs were found in 6 of 21
At pathologic examination, 15 PTGs (19%)
ular hyperplasia. Table 1 shows the number of
PTGs detected and removed, surgical procedure,
follow-up, and outcome for each patient.
Eleven of 21 patients (53%) included in the
study had concomitant echographic thyroid abnor-
malities, and 5 patients (24%) had a multinodular
goiter (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 20101229
In 4 of 5 patients, a papillary carcinoma was
detected (1 pT3 multifocal papillary carcinoma, 1
clear cell papillary carcinoma with a diameter of
0.9 cm, 1 microfocal papillary carcinoma with a
diameter of 0.1 cm, 1 multinodular and bilateral
subcentimetral papillary carcinoma). One infil-
trating papillary carcinoma was suspected on
preoperative ultrasonography; another case was
detected during surgical exploration. In these 2
cases, a central compartment lymphectomy was
performed. The remaining 2 cases were inciden-
tally identified at definitive histology.
One case of persistent SHPT (5%) was
observed as well as 2 cases of relapse of SHPT
(9%). No deaths or major postoperative compli-
cations were observed.
of the 78 PTGs that were removed surgically. Sim-
ilarly, scintigraphy detected 49 of 78 PTGs. As
shown in Table 2, of the 43 PTGs detected by
ultrasound, 8 were not detected by scintigraphy.
Of the 49 PTGs detected by scintigraphy, 14 were
not detected by ultrasound. In all, 57 PTGs were
detected by ultrasonography or scintigraphy.
Sestamibi scintiscans had a sensitivity and
specificity of 62% and 95%, and ultrasonography
of 55% and 95%, respectively. The differences
were not statistically significant. The association
of ultrasonography and scintigraphy had a sen-
The PTG size and the PTG diameter detected
on ultrasound and on pathologic examination
were significantly correlated (r ¼ .596; p <
.0001, 95% confidence interval [CI] 0.4286 to
0.7245). As expected, the mean histological
MLD of PTG visualized by ultrasonography and
scintigraphy was higher than that of missed
ones (Table 3).
The scintigraphy was positive in 25% of PTG
with diffuse hyperplasia, in 62% of PTGs with
early micronodular hyperplasia, and in 100% of
cases of adenoma-like hyperplasia (chi-square
test, p < .005) (see Figure 4) The mean ? SD
ultrasound 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 PTGs
localized in atypical sites, ultrasonography was
always negative, whereas scintigraphy was posi-
tive in 7/9 (78%) of cases.
The sonography and scintigraphy sensitiv-
ities were similar in patients with and without
concomitant thyroid diseases. Conversely, ultra-
sonography and scintigraphy specificities were
lower in patients with concomitant thyroid dis-
ease. The scintigraphy was falsely positive in 1
patient (5%) with a voluminous oxyphil ade-
noma in multinodular goiter.
Ultrasonography detected 43
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.]
1230Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hed September2010
Three intraoperative frozen sections were
performed when the ultrasonography and scin-
tigraphy were positive, whereas 20 frozen sec-
tions were performed when ultrasonography
and scintigraphy were negative (p < .0001).
Likewise, frozen sections were more frequently
performed when the PTGs were located in atypi-
cal rather than in typical sites.
The present study shows that the combination
of ultrasonography and 99mTC sestamibi scin-
tigraphy for the preoperative localization of
parathyroid glands in SHPT has a higher sensi-
tivity than ultrasonography or sestamibi scintig-
raphy alone. Furthermore, the combination of
these imaging techniques is particularly useful
and complementary in the planning of the surgi-
cal strategy of uremic SHPT—if we consider the
frequency of patients with concomitant thyroid
diseases (24%), ectopic (29%), and supernumer-
ary glands (10%).
These data are in accord with recent reports
in which the sensitivity of the combination of
the 2 imaging techniques proved to be signifi-
cantly better than that of the single proce-
dures.28–32It is useful to be reminded that the
operators of each of the imaging techniques
were blind to the results of the other exam.
Thus, it is possible that the sensitivity and spec-
ificity are underestimated. Taking into account
these considerations, we propose to perform first
the less operator-dependent scintigraphy, and
thereafter the ultrasonography. In this way, the
radiologist may be easily guided to areas with
suspicious parathyroid tissue.
However, it seems difficult to localize all
PTGs by ultrasonography and scintigraphy in
SHPT because PTG hyperplasia is an asynchro-
nous and asymmetrical process.
As previously reported,34–40the PTG site
(superior or inferior, typical or ectopic), the
Table 1. Number of PTGs detected and removed in each patient by PTX and outcome.
resectionThyroid diseaseFollow-up ResultsDetected Removed
MNG microfocal papillary Ca.
3 and 1/2
3 and 1/2
3 and 1/2
3 and 1/2
3 and 1/2
TotalMNG papillary Ca.
Total MNG oxyphil adenoma þ
microfocal papillary Ca.
MNG papillary Ca. pT3m 16
T þ A
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.
No. by scintigraphy
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 <
Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hedSeptember20101231
diameter, and the type of hyperplasia are the
main factors determining the ultrasonography
patterns and scintigraphy uptake. With regard
to the site, the present study confirms that, de-
spite a similar MLD, the percentage of PTGs
visualized by ultrasonography and scintigraphy
was higher for inferior than that for superior
PTG. Possibly, the superior PTGs are usually
localized at the level of the thyrolaryngeal
groove, a site explorable by ultrasonography
only with some difficulty. In addition, superior
PTGs are just behind thyroid lobes and closed to
the thick thyroid tissue. This makes identifica-
tion by scintigraphy difficult.
With regard to the type of hyperplasia, the
MIBI sensitivity was 67% and 100% for micro-
nodular and macronodular hyperplasia, respec-
tively, and 25% for diffuse hyperplasia. These
data agree with those of Nishida et al,41who
recently reported 28% of positive scintigraphy in
diffuse hyperplasia. Accordingly, it has been
shown that the number of the mitosis and cell
proliferation, of the oxyphil cells and mitochon-
dria prevailing in the advanced forms of PTG
hyperplasia facilitates the cellular sestamibi
uptake.36As suggested by Fuster et al,22the dif-
ferent MIBI uptake in diffuse or nodular hyper-
identification and surgical evaluation of the
PTG to partially spare in case of subtotal
Finally, in accord with other reports, we
found that the PTG diameter is a very impor-
tant predictive factor of nodular hyperplasia
a useful element for
and MIBI uptake. We have observed that PTG
with MLD < 8 mm and absent MIBI uptake
usually showed diffuse hyperplasia. The encour-
aging surgical outcome of this series is possibly
explained by the fact that PTG with a diameter
>10 mm or with positive MIBI uptake were
never left in site or reimplanted.
Another finding of the present study is that
in the localization of ectopic PTG, the scintigra-
phy sensitivity is very high, whereas the ultra-
sonography sensitivity is null. Ultrasonography
always failed to detect PTG localized in atypical
sites, whereas scintigraphy was positive in 78%
of cases, although the mean MLD of PTG was
7.8 ? 2.2 mm. Thus, scintigraphy is the only
imaging technique that can identify ectopic
glands 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 an
ectopic focus. The data are yet limited. However,
the 2009 European Association of Nuclear Medi-
cine (EANM) guidelines42suggest that although
SPECT and SPECT/CT imaging are becoming
very helpful, they cannot replace the standard
planar and ‘‘pinhole’’ protocols that are still
essential for optimal resolution in the thyroid
bed region and for a correct diagnosis.
Patients with SHPT have been found to have
a higher rate of ectopic and or supernumerary
PTG (20% to 43%) than those with primary
disease (6% to 18%).9,43–47However, it should be
stated that there are particularly insidious
ectopic glands that some authors define ‘‘major
ectopy.’’ As suggested by Mariani et al48the
term ‘‘major ectopy’’ refers to PTG located in
the mediastinum, or high in the neck, or lateral
to the cervical neurovascular bundle, or inside
the thyroid gland. This justifies the need for
Table 3. MLD (mean ? SD) of PTGs detected at pathology in
accord with ultrasonography and scintigraphy findings.
ModalityMLD, mean ? SD, mmp value
12.7 ? 0.7
9.3 ? 0.8
13.0 ? 0.7*
9.4 ? 0.8
8.3 ? 2.2*
Abbreviations: MLD, maximum longitudinal diameter; PTG, parathyroid
*t test, p < .03.
FIGURE 4. 99mTc sestamibi uptake in PTG with diffuse hyper-
plasia (25%) or nodular hyperplasia (85%).
1232Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hedSeptember2010
additional diagnostic techniques for surgical ex-
ploration. These ectopic PTGs are those that
most easily can be left in situ in the first
instance, since the routine technique of surgical
exploration does not expose these regions nor
does it usually include thyroidectomy. In the
present study, 3 major ectopic glands (1 intra-
thyroid and 2 retrofaringealesophageal) were
found that would have been hardly removed in
the absence of scintigraphic imaging.
Moreover, in 2 patients (10%) supernumerary
PTGs were found, confirming the reported data
about the increased frequency of supernumerary
PTGs in uremic SHPT (13% to 20%) compared
with normal subjects (5% to 13%).43–47Based on
all these considerations, we suggest the routine
use of ultrasound and sestamibi scans prior to
surgical exploration in SHPT.
These procedures may be associated with the
intraoperative parathyroid hormone (io-PTH)
assay. It is well known that the io-PTH assay
has been proposed to assess the adequacy of sur-
gery and to detect supernumerary glands. Obvi-
ously, the io-PTH assay is not able to indicate
the site of supernumerary glands eventually
Interestingly, in the present study we docu-
mented a reduction of the number of frozen sec-
ultrasonography and scintigraphy were positive,
with a consequent decrease of operative time
and economical costs. Estimated cost reduction
for each omitted frozen section was 100 euros in
our institution. The frozen sections were signifi-
cantly more frequent in cases of ectopic PTG or
reported that in 42 patients with negative imag-
ing a mean of 4 (range, 1–11) frozen sections per
patient were sent for pathologic examination.
To ensure the removal of all PTGs, Tominaga
et al6recommend the histological confirmation
during surgery in all cases. Of note, in the pres-
ent study, when ultrasonography and scintigra-
phy were both positive, histological examination
was always positive for PTG, suggesting that in
these cases the frozen sections may be avoided.
Finally, the utility to perform both ultraso-
nography and scintigraphy preoperatively in
patients with SHPT who are candidates for sur-
gery comes from the observation of concomitant
nodular thyroid disease in 24% of patients
included in the present study. The frequency of
association of thyroid nodular disease or carci-
noma with SHPT ranges between 3% and
37%.50–52Such association is considered casual
and similar to that of the general popula-
tion.15,53,54However, it is well known that the
detection of abnormal PTGs by both ultrasonog-
raphy and scintigraphy may be impaired in the
presence of nodular28,55,56or multinodular thy-
roid disease.16,39Indeed, we did not find signifi-
SHPT with and without concomitant thyroid dis-
ease. Conversely, the specificity of both methods
was 100% in SHPT without thyroid disease and
80% in SHPT with thyroid diseases. The high
prevalence of concomitant nodular thyroid dis-
ease in SHPT further supports the usefulness of
preoperative ultrasound in the correct assess-
ment of parathyroid and thyroid status in
patients with SHPT45and the adjunct of thyroid
scintigraphic imaging to the standard dual-
workup in several European countries with io-
In conclusion, the present study shows that
the combined use of ultrasound and MIBI
Table 4. Number of superior and inferior PTGs detected by ultrasonography, scintigraphy, and histology in typical and ectopic
Ectopic PTGs, no. (%)p valueSuperior, no. (%)Inferior, no. (%)Total
MLD at pathology
10.5 ? 4.6
12.4 ? 4.6
42 7 (78)
8.3 ? 2.2
11.5 ? 4.7 ns
Abbreviations: PTG, parathyroid gland; MLD, maximum longitudinal diameter; ns, not significant.
Ultrasonography and Scintigraphy in Secondary Hyperparathyroidism HEAD & NECK—DOI 10.1002/hedSeptember 20101233
scintigraphy in the preoperative evaluation of
end-stage renal disease patients with SHPT has
an higher sensitivity and leads to detection of
the ectopic and supernumerary PTG and con-
comitant thyroid disease, and to a significant
reduction of the number of intraoperative frozen
sections for histology.
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