Original article
Radioguided parathyroidectomy in patients with secondary
hyperparathyroidism due to chronic renal failure
Jun Chen and Jia-dong Wang
Objective The aim of the study was to determine the
effectiveness of radioguided parathyroidectomy in patients
with secondary hyperparathyroidism (sHPT) due to chronic
renal failure (CRF).
Methods Between August 2003 and October 2011, CRF
patients undergoing parathyroidectomy for sHPT received
conventional parathyroidectomy with preoperative
ultrasound localization or radioguided surgery. For
radioguided surgery, 370 MBq of 99mTc-sestamibi was
injected intravenously 1.52 h before surgery, and a gamma
probe was used intraoperatively to identify the parathyroid
glands by radioactivity count.
c 2014 Wolters Kluwer Health |
Results Twenty-five patients underwent conventional
parathyroidectomy and 25 underwent radioguided
parathyroidectomy. The median patient age was 55 years
(range, 3775 years). In the conventional surgery group,
the parathyroid glands were removed in 18 patients, and
seven patients experienced recurrence as determined
by intact parathyroid hormone (iPTH) levels. One patient
in the radioguided surgery group experienced recurrence
due to ectopic parathyroid tissue in the mediastinum. The
operative time of radioguided surgery was shorter than
that of conventional surgery [median (interquartile range),
100.0 (84.0118.0) vs. 114.0 (103.0134.0) min,
Introduction
Hyperparathyroidism (HPT) is one of the most common
endocrine disorders, and secondary HPT (sHPT) is
common in patients with chronic renal failure
(CRF) [1]. Renal impairment results in phosphorus
retention with subsequent hypocalcemia, which in turn
stimulates parathyroid hormone (PTH) secretion, and
renal damage prevents the kidneys from fully responding
to increased levels of PTH by activating tubular calcium-
sparing. Elevated phosphorus levels also inhibit the
calcemic action of PTH on skeletal muscle. These
factors, in addition to downregulation of PTH receptors
and increased calcitonin secretion, result in a hyperpar-
athyroid state [1]. With the widespread availability of
dialysis, the survival time of patients with CRF is
increasing, and as a result the incidence of sHPT is also
increasing. It is reported that approximately one in three
patients undergoing long-term dialysis is affected by
sHPT [24]. Drug treatment for sHPT due to CRF is
available at the early stage of the disease, but it is not as
effective for patients with later-stage disease. Once
complications including skeletal malformations, fractures,
0143-3636
c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
respectively; P = 0.015]. On postoperative day 1, iPTH
and serum calcium levels were significantly lower in the
radioguided surgery group than in the conventional surgery
group [median (interquartile range), iPTH: 3 (320) vs. 53
(11230) ng/l; P = 0.006, calcium: 1.72 (1.631.85) vs. 2.06
(1.922.12) mmol/l; P < 0.001]. Radioactivity counts
of parathyroid glands were significantly higher than
in thyroid tissue, lymph nodes, and fat (all, P < 0.001).
Conclusion Radioguided localization of the parathyroid
glands improves the success rate of surgery in patients
with CRF undergoing parathyroidectomy for sHPT. Nucl
Med Commun 35:391397
Lippincott Williams & Wilkins.
Nuclear Medicine Communications 2014, 35:391397
Keywords: chronic renal failure, hyperparathyroidism, MIBI scan
sestamibi scan
Department of Otolaryngology Head and Neck Surgery, Shanghai RenJi hospital,
School of Medicine, Shanghai JiaoTong University, Shanghai, China
Correspondence to Jia-dong Wang, MD, Department of Otolaryngology Head
and Neck Surgery, Shanghai RenJi hospital, Shanghai JiaoTong University,
#1630, Dongfang Road, Pudong New District, Shanghai 200127, China
Tel: + 86 136 018 55150; e-mail: drjiadongw@aliyun.com
Received 18 September 2013 Revised 7 November 2013
Accepted 9 November 2013
and extensive metastatic calcification in the cardiovas-
cular system have occurred, the quality of life of the
patients will be affected and life expectancy will be
reduced [1].
Although subtotal parathyroidectomy can be performed,
studies have shown that the effect of subtotal parathyr-
oidectomy is less than ideal as compared with total
parathyroidectomy with autotransplantation. Serum cal-
cium and alkaline phosphatase levels are more likely to
normalize after total parathyroidectomy with autotrans-
plantation, recurrence is more common with subtotal
parathyroidectomy, and reoperation in the autograft in
the forearm is much simpler than reoperation in the
neck [2,5]. Because of their small size, localization of
parathyroid glands using ultrasound, computed tomogra-
phy (CT), or MRI is difficult [68], although precise
localization of the parathyroid glands allows complete
resection and improves the result of parathyroidectomy.
Technetium (99mTc)-sestamibi scanning (MIBI) is the
primary method used for localization of hyperfunctioning
parathyroid glands [9,10], and as little as 100 mg of
DOI: 10.1097/MNM.0000000000000062
392 Nuclear Medicine Communications 2014, Vol 35 No 4
hyperfunctioning parathyroid gland tissue can be de-
tected [10]. However, imaging is not always reliable and
false-negative results are possible. Radioguided resection
of the hyperfunctioning parathyroid glands involves the
preoperative intravenous injection of 99mTc-sestamibi,
and intraoperatively a hand-held gamma probe is used to
facilitate localization of hyperfunctioning parathyroid
tissue. The technique has been used successfully for
the removal of parathyroid adenomas and has reduced the
need for extensive surgical exploration [1116]. However,
there are no reports on the use of radioguided surgery for
the resection of all four parathyroid glands as is necessary
for the treatment of sHPT in patients with CRF.
The purpose of this study was to compare the results of
radioguided resection of the parathyroid glands with
those of conventional surgical removal in patients
with CRF and sHPT.
Patients and methods
Patients
Between March 2003 and September 2011, we performed
total parathyroidectomy with autotransplantation in 50
consecutive patients with sHPT due to CRF. The
50 patients were assigned to conventional parathyroi-
dectomy with ultrasound localization or radioguided
parathyroidectomy by alternating patients between
groups. Patients with primary HPT were excluded from
this study. This study was approved by the Institutional
Review Board of the hospital, and all patients provided
written informed consent.
In all patients, conventional treatments such as dietary
restriction and vitamin D therapy failed to decrease the
serum PTH level. All patients in both groups received
preoperative ultrasound localization of the parathyroid
glands and underwent examination of the thyroid gland.
Patients in the radioguided surgery group who provided
consent also underwent preoperative 99mTc-sestamibi
scans. No gamma camera scanning was performed
preoperatively.
All the patients were hemodialyzed the day before
surgery and 1 or 2 days after the surgery; thereafter, their
normal dialysis schedule was resumed. Before surgery all
patients were administered calcitriol to decrease the
secretion of PTH.
99m
Preoperative Tc-sestamibi scanning protocol
Double-phase 99mTc-MIBI imaging (1530 min, early
phase; 90120 min, late phase) was performed preopera-
tively in patients who provided consent. A dosage of
370 MBq was injected intravenously to perform neck and
upper chest and anterior planar imaging; lateral imaging
was performed if necessary. Machine settings were as
follows: matrix 256  256, magnification  23, and
acquisition time 300 s (Infinia Hawkeye 4 SPECT/CT
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
scanner; GE Healthcare, Pewaukee, Wisconsin, USA).
Image fusion acquisitions were collected for patients with
abnormal uptake of radioactivity outside of thyroid
lesions. For image fusion acquisitions, the scan field was
adjusted to the patients neck and upper chest for nuclear
medicine acquisitions and the settings were matrix
128  128, magnification  1.5, 60 frames, 40 s/frame,
and rotation 1800.
After the nuclear medicine acquisition was completed,
the nuclear medicine instrument with an automatic scan
horizon bed was rotated to a certain position so that CT
scanning and vision-y imaging could be performed in the
same Ci. Single-photon emission computed tomography
and CT images were obtained through computer proces-
sing of the respective transverse, coronal, and sagittal
images, as well as of the corresponding fused image.
Surgical procedure
Surgery was performed under general anesthesia. Briefly,
in both groups a frontal cervical transverse incision was
made, similar to that for thyroidectomy, and the tissues
were dissected in a stepwise manner until the thyroid
gland was exposed. The middle thyroid veins were
ligated, and the thyroid gland was turned over medially.
In patients undergoing conventional parathyroidectomy,
intraoperative exploration and preoperative ultrasound
findings were used to identify the hyperplastic parathyr-
oid glands, which were then dissected and removed.
For patients undergoing radioguided parathyroidectomy,
370 MBq of 99mTc-sestamibi was injected intravenously
1.52 h before surgery. This is the standard dose used at
our institution and is similar to that reported by other
authors [17]. In the operating room, background radio-
activity counts were obtained by placing a gamma probe
on the thyroid isthmus before making the surgical
incision. After the incision, intraoperative scanning was
performed to detect background radioactivity counts to
locate the abnormal parathyroid glands. For in-vivo
scanning, the probe was placed such that it was directly
facing the suspicious glands during surgery, and the
counts were noted. The counts obtained by scanning the
identified hyperplastic parathyroid gland in situ were
defined as in vivo counts and were expressed as a
percentage of the background count. A number of
techniques were used to address the potential of scatter
from organs with high counts. A more sophisticated probe
was used. The suspicious glands were completely
separated from the surrounding tissue to avoid any
interference of radioactivity from the surrounding tissue.
In addition, the surgical field was irrigated with normal
saline before probing to avoid interference by blood.
Hyperplastic parathyroid glands and adenomatous glands
were excised. After excision of the parathyroid gland, the
tissue was placed on top of the gamma probe (directed
away from the patient) to determine ex vivo counts.

Ex-vivo counts were expressed as a percentage of the
background count. Biopsy of normal thyroid tissue, lymph
nodes, and fat was also performed and the radioactivity of
the tissues was tested as described for the parathyroid
glands. All excised tissues in both groups were sent for
histopathological analysis.
Autotransplantation was performed in all patients. Glands
with a relatively healthy color, with a good blood supply,
and with a normal texture were used for autotransplanta-
tion. In brief, 30 pieces of sliced hyperplastic glands
(1 mm3) were implanted into muscles in the forearm
without the arteriovenous fistula for hemodialysis.
Postoperative care
Intact PTH (iPTH), calcium, and phosphorus levels were
measured before the surgery and then again 1 day
postoperatively, and patients complications were fol-
lowed up at 3 months after surgery. Serum calcium
concentration was monitored 12 times/day in the
immediate postoperative period. To prevent transient
hypocalcemia after the removal of all parathyroid glands,
every patient was given an intravenous calcium supple-
ment postoperatively to maintain adequate calcium
levels. The protocol for calcium administration after
parathyroidectomy depended on the calcium levels after
the surgery. Calcium gluconate, 1020 g/24 h, was admi-
nistered for 35 days, and then an oral calcium
supplement was administered. Patient symptoms related
to sHPT were monitored before surgery and postopera-
tively.
Data analysis
Continuous variables were summarized by median with
interquartile range (IQR, the range between the 25 and
75th percentile) because of the small sample size or non-
normality of data; categorical variables were expressed in
frequencies and percentages. Differences between pa-
tients in the two groups were detected by the Wilcoxon
rank sum test for continuous variables and by the w2-test
or Fishers exact for categorical variables, as appropriate.
Changes in preoperative and postoperative symptoms
relevant to sHPT were detected by MacNemars test.
Differences in in-vivo counts or ex-vivo counts (% of
background count) were compared using the Kruskal
Wallis test with Bonferronis post-hoc test among four
different tissues (hyperplastic parathyroid, thyroid tissue,
lymph nodes, and fat) and using the Wilcoxon rank sum
test between parathyroid glands with different MIBI scan
results (positive vs. negative). The proportions of ex-vivo
counts greater than 20% of the background count among
four different tissues were compared using Fishers exact
test. Statistical analyses were performed with SAS
software, version 9.2 (SAS Institute Inc., Cary, North
Carolina, USA). A two-tailed P-value less than 0.05
indicated statistical significance.
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Radioguided parathyroidectomy in sHPT Chen and Wang 393
Results
Patient demographics and clinical characteristics
A total of 50 patients (31 male and 19 female) with a
median age of 55 years (range, 3775 years) who
underwent parathyroidectomy with autotransplantation
were included in this study. Twenty-five patients under-
went conventional parathyroidectomy and 25 underwent
radioguided parathyroidectomy. The median time of
sHPT was 9 years (range, 515 years), and the median
time of dialysis was 8 years (range, 415 years). The
median follow-up time was 25.5 months (range, 336
months). Patient data are summarized in Table 1.
Patients in the two groups did not differ with respect to
age, sex, length of disease, duration of dialysis, length of
hospital stay, or length of follow-up (all, P > 0.05).
Surgical outcomes and intact parathyroid hormone,
calcium, and phosphorus levels
In the conventional surgery group, parathyroid glands
were removed from 18 patients, and seven patients
experienced recurrence as determined by iPTH levels at
3 weeks to 4 months after the surgery because of remnant
glands. In these seven patients, recurrence was due to
residual parathyroid glands and in these patients three
glands were resected in six patients and four glands were
resected in one patient. Postoperatively, a decrease in
PTH level was observed in all of these patients, but it did
not decrease to the normal range.
In the radioguided surgery group, all glands were removed
in 24 patients and none of the 24 patients experienced
recurrence as determined by postoperative iPTH levels.
One patient experienced recurrence as a result of an
ectopic gland in the mediastinum, which was identified
on parathyroid scintigraphy. Patients who underwent
radioguided surgery had a significantly shorter operative
time [median (IQR), 100.0 (84.0118.0) vs. 114.0
(103.0134.0) min, respectively; P = 0.015] and lower
recurrence rate (4.0 vs. 28.0%, respectively; P = 0.049)
compared with those who underwent conventional
surgery (Table 1). No serious intraoperative or post-
operative complications such as recurrent laryngeal nerve
damage, wound infection, or massive hemorrhage oc-
curred in any patients.
Preoperative iPTH, calcium, and phosphorus levels were
not different between the two groups (all, P > 0.05). On
postoperative day 1, iPTH and serum calcium levels were
significantly lower in the radioguided surgery group as
compared with the conventional surgery group [median
(IQR), iPTH: 3 (320) vs. 53 (11230) ng/l, respectively;
P = 0.006, calcium: 1.72 (1.631.85) vs. 2.06 (1.922.12)
mmol/l, respectively; P < 0.001]. Moreover, patients in
the radioguided surgery group showed a more profound
decrease in iPTH level [median (IQR), 99.8 ( 99.9 to
99.1) vs. 97.5 ( 99.6 to 89.1)%, respectively;
P = 0.006] and calcium level [median (IQR), 29.4
394 Nuclear Medicine Communications 2014, Vol 35 No 4

Table 1 Patient demographic and laboratory data

Conventional surgery (n = 25) Radioguided surgery (n = 25) P-value
Demographic characteristics
Age (years) 56.0 (48.061.0) 55.0 (51.060.0) 0.969wb
Sex
Male 15 (60.0) 16 (64.0) 0.771c
Female 10 (40.0) 9 (36.0)
Laboratory data
Preoperative iPTH (pmol/l) 232.03 (207254) 249.84 (223265) 0.325b
Postoperative iPTH (day 1) (pmol/l) 5.62 (1.224.4) 0.32 (0.322.12) 0.006b
Percentage changea in iPTH (%) 97.5 ( 99.6 to 89.1) 99.8 ( 99.9 to 99.1) 0.006b
Preoperative serum calcium (mmol/l) 2.44 (2.342.64) 2.47 (2.372.79) 0.336b
Postoperative serum calcium (day 1) (mmol/l) 2.06 (1.922.12) 1.72 (1.631.85) < 0.001b
Percentage changea in serum calcium (%) 17.9 ( 22.1 to 13.3) 29.4 ( 36.1 to 25.7) < 0.001b
Preoperative serum phosphorus (mmol/l) 2.26 (2.192.39) 2.35 (2.232.53) 0.210b
Postoperative serum phosphorus (day 1) (mmol/l) 1.64 (1.521.74) 1.61 (1.441.72) 0.356b
Percentage changea in serum phosphorus 29.4 ( 34.2 to 23.7) 31.8 ( 43.3 to 23.7) 0.322b
Clinical data
Course of the disease (years) 9.0 (8.012.0) 9.0 (8.012.0) 0.822b
Duration of dialysis (years) 8.0 (7.09.0) 8.0 (7.09.0) 0.333b
Operative time (min) 114.0 (103.0134.0) 100.0 (84.0118.0) 0.015b
Hospital stay (days) 5.0 (4.05.0) 4.0 (4.05.0) 0.131b
Follow-up time (months) 26.0 (21.028.0) 25.0 (17.030.0) 0.437b
Recurrence 7 (28.0) 1 (4.0) 0.049d

Data are presented as median (interquartile range) or number (percentage).

iPTH, intact parathyroid hormone.
a
Percentage change = [(post pre)/pre]  100%.
b
Wilcoxon rank sum test.
c 2
w -test.
d
Fishers exact test.

( 36.1 to 25.7) vs. 17.9 ( 22.1 to 13.3)%,
respectively; P < 0.001] on postoperative day 1 compared
with those in the conventional surgery group (Table 1).
Postoperative phosphate levels were not significantly
different between the two groups (Table 1).
Symptoms relevant to secondary hyperparathyroidism
Symptoms relevant to sHPT are summarized in Table 2.
Before surgery, the most frequently reported symptoms in
the conventional surgery group were fatigue (80%), bone
pain (72%), movement disorder (40%), and renal stones
(40%), and those in the radioguided surgery group were
fatigue (96%), bone pain (76%), and movement disorder
(56%). Postoperatively, patients in both groups experi-
enced significant improvement in symptoms of renal
stones, bone pain, movement disorder, fatigue, and
pruritus (all, P < 0.05). No significant difference, however,
was found in preoperative or postoperative symptoms
between the two groups.
Radioactivity in resected tissues: in-vivo and ex-vivo
counts
A total of 196 hyperfunctioning parathyroid glands were
resected from the 50 patients: 95 in the conventional
surgery group and 101 in the radioguided surgery group.
In addition, in the radioguided surgery group 20 samples
of thyroid tissue, 15 lymph nodes, and 18 samples of fat
were resected. Histopathological examination of all
tissues removed in both groups was performed to confirm
the diagnosis. The levels of radioactivity among four
types of tissue resected in the radioguided surgery group
are shown in Table 3. The in-vivo and ex-vivo radio-
activity counts in the hyperplastic parathyroid glands
were significantly higher than that in thyroid tissue,
lymph nodes, and fat (all, P < 0.001). In addition, the
counts in thyroid tissue and lymph nodes were also
significantly higher than that in fat (both, P < 0.05). All
hyperplastic parathyroid glands had ex-vivo counts greater
than 20% of the background count, whereas the other
three types of tissue had ex-vivo counts less than 20%
of the background count (all, P < 0.001). We did not
encounter any issues with scatter from organs with high
counts.
Preoperative MIBI scans
A total of 66 parathyroid glands in the radioguided surgery
group received a preoperative MIBI scan, and of these 24
scans were negative and 42 were positive. A representa-
tive positive scan is shown in Fig. 1. All 66 glands were
found to be hyperplastic on pathological examination and
had elevated intraoperative radioactivity counts; thus, the
sensitivity of the preoperative MIBI scanning was 64%
(42/66). Parathyroid glands with either negative or
positive MIBI scans had in-vivo radioactivity counts
greater than 100% of the background count. Parathyroid
glands with positive scans had in-vivo and ex-vivo
radioactivity counts that were significantly greater than
those with negative scans (Table 4). Moreover, all 66
parathyroid glands had ex-vivo counts greater than 20%
of the background count.
Discussion
The results of this study showed that radioguided surgical
removal of the parathyroid glands in patients with sHPT

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 Radioguided parathyroidectomy in sHPT Chen and Wang 395

Table 2 Preoperative and postoperative symptoms associated with secondary hyperparathyroidism

Conventional surgery (n = 25) Radioguided surgery (n = 25)

Symptom Preoperative Postoperative day 1 P-valuea Preoperative Postoperative day 1 P-valuea

None 1 (4.0) 3 (12.0) 0.157 0 (0.0) 2 (8.0) NA
Renal stones 10 (40.0) 5 (20.0) 0.025 12 (48.0) 4 (16.0) 0.005
Hypertension 5 (20.0) 4 (16.0) 0.317 6 (24.0) 4 (16.0) 0.157
Bone pain 18 (72.0) 5 (20.0) < 0.001 19 (76.0) 3 (12.0) < 0.001
Movement disorder 10 (40.0) 5 (20.0) 0.025 14 (56.0) 9 (36.0) 0.025
Fatigue 20 (80.0) 12 (48.0) 0.005 24 (96.0) 11 (44.0) < 0.001
Depression 5 (20.0) 4 (16.0) 0.317 4 (16.0) 4 (16.0) NA
Nervousness 3 (12.0) 2 (8.0) 0.317 2 (8.0) 2 (8.0) NA
Ulcer disease 1 (4.0) 1 (4.0) NA 0 (0.0) 0 (0.0) NA
Anorexia 8 (32.0) 5 (20.0) 0.083 12 (48.0) 9 (36.0) 0.083
Pruritus 7 (28.0) 2 (8.0) 0.025 6 (24.0) 1 (4.0) 0.025

Data are presented as number (percentage).

NA, not applicable.
a
McNemars test.

Table 3 In-vivo and ex-vivo radioactivity counts between different tissues in the radioguided surgery group
Pathological diagnosis of excised tissue

Hyperplastic parathyroid (n = 101) Thyroid tissue (n = 20) Lymph node (n = 15) Fat (n = 18) P-value
In-vivo counts (% background) 154.0 (125.0182.0)a,b,c 74.5 (68.577.5)c 68.0 (59.077.0)c 51.5 (44.063.0) < 0.001d
Ex-vivo counts > 20% background 101 (100.0)a,b,c 0 (0.0) 0 (0.0) 0 (0.0) < 0.001e
Ex-vivo counts (% background) 81.0 (52.0111.0)a,b,c 8.0 (6.511.5)c 7.0 (4.012.0)c 2.0 (1.03.0) < 0.001d

Data are presented as median (interquartile range) or number (percentage).

a
P < 0.05 compared with thyroid tissue.
b
P < 0.05 compared with lymph node.
c
P < 0.05 compared with fat.
d
KruskalWallis test.
e
Fishers exact test.

Fig. 1

WEN DA XUAN N010926 PARATHYROID August 19, 2013 Shanghai Renji Hospital

R L R L

20 min 120 min

A representative case with a positive preoperative 99mTc-MIBI scintigraphy scan. The report of this patient did not show obvious abnormality in the
parathyroid glands; however, through the intraoperative 99mTc-MIBI scintigraphy, abnormal proliferation of four glands was observed.

due to CRF was more effective than conventional surgery removal in only 18 of 25 patients in the conventional
with preoperative ultrasound localization. Using the surgery group. In addition, surgical time and recurrence
radioguided technique all hyperfunctioning glands were rate were both significantly lower in the radioguided
removed in 24 of 25 patients as compared with complete surgery group. Of note, the one recurrence in the

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396 Nuclear Medicine Communications 2014, Vol 35 No 4
Table 4 In-vivo and ex-vivo radioactive counts between parathyroid glands with positive and negative MIBI scans in the radioguided
surgery group
Negative scan (n = 24)
In-vivo count (% background) 123.0 (114.0140.5)
Ex-vivo count > 20% background 24 (100.0)
Ex-vivo count (% of background) 43.0 (34.052.0)
Data are presented as median (interquartile range) or number (percentage).
NA, not applicable.
wWilcoxon rank sum test.
radioguided surgery group was due to ectopic tissue in
the mediastinum, thus highlighting the importance of
ruling out ectopic parathyroid tissue.
The most common method of treating sHPT is
parathyroidectomy; however, surgery is complicated
because the glands are small and localization is difficult.
Normally, there are four parathyroid glands that measure
B6  4  2 mm and divided into two pairs distributed
symmetrically on each side of the thyroid. However, in
some cases one or more extra parathyroid glands are
present, and ectopic parathyroid tissue can also occur.
Because the parathyroid glands are small, and extra or
ectopic glands may be present, it is challenging to excise
all of the glands using only intraoperative exploration. In
addition to the postoperative hyperplasia of transplanted
tissues, the presence of remnant glands is the most
common cause of sHPT recurrence [2,3,18]. Thus, one of
the key factors for a successful operation is precise
localization of the parathyroid glands so that they are
totally excised. To prevent recurrence, it is essential to
remove all of the hyperplastic parathyroid tissue.
Commonly used imaging methods for the preoperative
localization of parathyroid glands include ultrasonography,
CT, MRI, and MIBI imaging [68]. Enlarged parathyroid
glands show nodular, hypoechoic, and homogenous
images on ultrasonography, and the overall sensitivity of
ultrasound for the detection of parathyroid adenomas is
7080% [19,20] and that for the detection of enlarged
glands is 3090% [16]. Advantages of ultrasound are that
it is noninvasive, the cost is low, and no ionizing radia-
tion is used; however, it is highly dependent on
the experience of the operator; accuracy varies with the
location of the parathyroid gland, and other structures in
the neck can mimic parathyroid enlargement. False-
negative results for ultrasound depend on the volume and
location of the glands and on the skill of the operator [15].
The overall sensitivity of CT for preoperative identifica-
tion of hyperplastic parathyroid glands ranges between 46
and 80%, with higher sensitivities associated with
intravenous contrast enhancement because adenomas
and hyperplastic parathyroid glands are hypervascu-
lar [7,8]. MRI is ineffective for the imaging of normal
parathyroid glands because of their small size, whereas
enlarged parathyroid glands display a medium intensity
on T1-weighted images but have increased intensity
on T2-weighted and proton density images; however,
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Positive scan (n = 42) P-valuew
174.5 (154.0190.0) < 0.001
42 (100.0) NA
96.5 (78.0122.0) < 0.001
distinguishing parathyroid adenomas from simple hyper-
plasia or carcinoma is not reliable [6,7]. Intraoperative
measurement of iPTH can be used to assess an
inadequate resection; a high level of iPTH after the
resection may suggest the incomplete removal of
the glands, or the existence of ectopic glands [18,21].
However, this test is not widely used in developing
countries because of the cost.
MIBI scanning is the most common method used for
parathyroid localization. The uptake of 99mTc-sestamibi
in hyperplastic or adenomatous parathyroid glands is
related to blood flow, gland size, and mitochondrial
activity [7,8,10,22]. Although 99mTc-sestamibi rapidly
accumulates both in thyroid and parathyroid tissue, it is
released much faster from thyroid than from parathyroid
tissue. With the appropriate technique, as little as 100 mg
of hyperfunctioning parathyroid gland can be de-
tected [10]. The combination of ultrasonography and
MIBI scanning may improve the detection rate of
hyperplastic parathyroid glands and adenomas [7,9].
Radioguided parathyroidectomy has been described
primarily for treatment of primary HPT, and many reports
have shown the effectiveness of this technique in
patients with parathyroid adenomas [1113,23]. Chen
et al. [24] reported the results of 669 patients with
primary HPT who had preoperative MIBI scans and who
underwent radioguided parathyroidectomy using a hand-
held gamma probe. All enlarged parathyroid glands were
localized with the gamma probe in patients with negative
and positive MIBI scans with similar sensitivity. The
technique has also proven useful in patients with prior
neck surgery [25].
Using the gamma probe, we were able to determine
whether the resected tissue was composed of hyperplas-
tic parathyroid gland, because all hyperplastic parathyroid
glands had ex-vivo counts that were greater than 20% of
the background counts, and other tissues had counts that
were all lower than 20% of the background counts [14].
Because we did not need to wait for frozen sections for
identification of excised tissue [21], the operative time
was relatively short. Similar to the results of Chen
et al. [24], we found that radioguided techniques are
equally effective in patients with negative and positive
MIBI scans. Thus, technologies such as radioguided
surgery have the potential to aid surgeons in these

potentially difficult cases. In addition, forearm graft
hyperplasia can be detected using 99mTc-sestamibi
scanning [2628].
The primary limitation of the study is the relatively small
number of patients. In addition, not all patients in the
radioguided surgery group received preoperative MIBI
scans.
Conclusion
Radioguided localization of the parathyroid glands
improves the success rate of surgery and outcomes in
patients with CRF undergoing parathyroidectomy for
sHPT. The technique provides faster and more accurate
localization of hyperplasic parathyroid glands during
surgery.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
References
1 Drueke TB. Cell biology of parathyroid gland hyperplasia in chronic renal
failure. J Am Soc Nephrol 2000; 11:11411152.
2 Rothmund M, Wagner PK, Schark C. Subtotal parathyroidectomy versus
total parathyroidectomy and autotransplantation in secondary
hyperparathyroidism: a randomized trial. World J Surg 1991; 15:745750.
3 Hargrove GM, Pasieka JL, Hanley DA, Murphy MB. Short- and long-term
outcome of total parathyroidectomy with immediate autografting versus
subtotal parathyroidectomy in patients with end-stage renal disease. Am J
Nephrol 1999; 19:559564.
4 Saunders RN, Karoo R, Metcalfe MS, Nicholson ML. Four gland
parathyroidectomy without reimplantation in patients with chronic renal
failure. Postgrad Med J 2005; 81:255258.
5 Tominaga Y. Surgical management of secondary hyperparathyroidism in
uremia. Am J Med Sci 1999; 317:390397.
6 Chien D, Jacene H. Imaging of parathyroid glands. Otolaryngol Clin North
Am 2010; 43:399415.
7 Phillips CD, Shatzkes DR. Imaging of the parathyroid glands. Semin
Ultrasound CT MR 2012; 33:123129.
8 Vazquez BJ, Richards ML. Imaging of the thyroid and parathyroid glands.
Surg Clin North Am 2011; 91:1532.
9 Kunstman JW, Kirsch JD, Mahajan A, Udelsman R. Clinical review:
parathyroid localization and implications for clinical management. J Clin
Endocrinol Metab 2013; 98:902912.
10 Ugur O, Bozkurt MF, Rubello D. Nuclear medicine techniques for radio-
guided surgery of hyperparathyroidism. Minerva Endocrinol 2008; 33:
95104.
11 Costello D, Norman J. Minimally invasive radioguided parathyroidectomy.
Surg Oncol Clin N Am 1999; 8:555564.
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Radioguided parathyroidectomy in sHPT Chen and Wang 397
12 Norman J, Chheda H. Minimally invasive parathyroidectomy facilitated by
intraoperative nuclear mapping. Surgery 1997; 122:9981003.
13 Rubello D, Casara D, Giannini S, Piotto A, Dalle Carbonare L, Pagetta C,
et al. Minimally invasive radioguided parathyroidectomy: an attractive
therapeutic option for elderly patients with primary hyperparathyroidism.
Nucl Med Commun 2004; 25:901908.
14 Chen H, Mack E, Starling JR. Radioguided parathyroidectomy is equally
effective for both adenomatous and hyperplastic glands. Ann Surg 2003;
238:332337.
15 Mariani G, Gulec SA, Rubello D, Boni G, Puccini M, Pelizzo MR, et al.
Preoperative localization and radioguided parathyroid surgery. J Nucl Med
2003; 44:14431458.
16 Casara D, Rubello D, Pelizzo MR, Shapiro B. Clinical role of 99mTcO4/MIBI
scan, ultrasound and intra-operative gamma probe in the performance of
unilateral and minimally invasive surgery in primary hyperparathyroidism. Eur
J Nucl Med 2001; 28:13511359.
17 Arici C, Cheah WK, Ituarte PH, Morita E, Lynch TC, Siperstein AE, et al. Can
localization studies be used to direct focused parathyroid operations.
Surgery 2001; 129:720729.
18 Chou FF, Lee CH, Chen JB, Hsu KT, Sheen-Chen SM. Intraoperative
parathyroid hormone measurement in patients with secondary
hyperparathyroidism. Arch Surg 2002; 137:341344.
19 Ammori BJ, Madan M, Gopichandran TD, Price JJ, Whittaker M,
Ausobsky JR, et al. Ultrasound guided unilateral neck exploration for
sporadic primary hyperparathyroidism: is it worthwhile? Ann R Coll Surg
Engl 1998; 80:433437.
20 Geatti O, Shapiro B, Orsolon PG, Proto G, Guerra UP, Antonucci F, et al.
Localization of parathyroid enlargement: experience with technetium 99m
methoxyisobutylisonitrile and thallium-201 scintigraphy, ultrasound and
computed tomography. Eur J Nucl Med 1994; 21:1723.
21 Goldstein RE, Billheimer D, Martin WH, Richards K. Sestamibi scanning and
minimally invasive radioguided parathyroidectomy without intraoperative
parathyroid hormone measurement. Ann Surg 2003; 237:722730.
22 Mordechai L, Tiberiu E, Pinhas S. Preoperative technetium Tc 99m sestamibi
SPECT imaging in the management of primary hyperparathyroidism in
patients with concomitant multinodular goiter. Arch Surg 2005; 140:
656660.
23 Usmani S, Khan HA, al Mohannadi S, Javed A, al Nafisi N, abu Huda F, et al.
Minimally invasive radionuclide-guided parathyroidectomy using 99mTc-
sestamibi in patients with primary hyperparathyroidism: a single-institution
experience. Med Princ Pract 2009; 18:373377.
24 Chen H, Sippel RS, Schaefer S. The effectiveness of radioguided
parathyroidectomy in patients with negative technetium Tc 99m-
sestamibi scan. Arch Surg 2009; 144:643648.
25 Sar S, Erbil Y, Ersoz F, Olmez A, Salmasloglu A, Adalet I, et al. Radio-
guided excision of parathyroid lesions in patients who had previous neck
surgeries: a safe and easy technique for re-operative parathyroid surgery.
Int J Surg 2011; 9:339342.
26 Chen H, Civelek AC, Westra WH, Scheel PJ, Udelsman R. Use of
technetium Tc 99m sestamibi scintigraphy for recurrent tertiary
hyperparathyroidism from a parathyroid forearm graft. South Med J 2000;
93:215217.
27 Cutress RI, Manwaring-White C, Dixon K, Dhir A, Skene AI. Gamma probe
radioguided parathyroid forearm surgery in recurrent hyperparathyroidism.
Ann R Coll Surg Engl 2009; 91:13.
28 Sippel RS, Bianco J, Chen H. Radioguided parathyroidectomy for recurrent
hyperparathyroidism caused by forearm graft hyperplasia. J Bone Miner Res
2003; 18:939942.