The Laryngoscope
C 2013 The American Laryngological,
V
Rhinological and Otological Society, Inc.
The Diagnostic Value of Parathyroid Hormone Washout After
Fine-Needle Aspiration of Suspicious Cervical Lesions in Patients
With Hyperparathyroidism
Ramsy Abdelghani, MD; Salem Noureldine, MD; Ali Abbas, MD, MPH; Krzysztof Moroz, MD;
Emad Kandil, MD, FACS
Objectives/Hypothesis: We aimed to study the diagnostic value of parathyroid hormone (PTH) concentration in the
needle washout of fine-needle aspiration (FNA) compared to cytology of suspicious lesions suggestive of culprit parathyroid
glands in patients with recurrent or persistent primary hyperparathyroidism (PHPT).
Study Design: Retrospective review.
Methods: Patients with recurrent or persistent PHPT, who were referred to one surgeon and underwent FNA of the
culprit parathyroid lesion preoperatively, were included in this study. All patients underwent comprehensive neck ultrasound,
and suspicious lesions underwent ultrasound-guided FNA by the same surgeon. The aspiration cytology was read by a single
dedicated cytopathologist blinded to the PTH washout results. A positive cutoff value for PTH washout concentration was
defined as superior to serum PTH level obtained at the same time. The final diagnosis after reoperative surgery was
confirmed by the same cytopathologist.
Results: Twenty-four consecutive patients were included. The mean serum PTH and calcium were 111.5 6 106.25
pg/mL (normal: 15–65 pg/mL) and 10.8 6 0.5 mg/dL (normal: 8.6–10.2 pg/mL), respectively. Twenty-two patients (91.6%)
had elevated PTH washout concentrations with a positive predictive value (PPV) of 100%. Cytopathology was successful in
confirming parathyroid tissue only in seven patients (29%). An adenoma was identified in 19 patients (79.1%); however, five
patients (20.8%) were found to have multiglandular disease.
Conclusions: An elevated PTH washout concentration can help identify culprit parathyroid gland lesions with a high
PPV in patients requiring reoperative parathyroid surgery. This diagnostic technique allows for targeted surgical approach in
reoperative settings, especially in patients with negative preoperative sestamibi scans.
Key Words: Hyperparathyroidism, fine-needle aspiration, parathyroid hormone, parathyroid assay, parathyroid
hormone washout, recurrent hyperparathyroidism, persistent hyperparathyroidism.
Level of Evidence: 4.
Laryngoscope, 123:1310–1313, 2013
INTRODUCTION
Primary hyperparathyroidism (PHPT) is one of the
most common endocrine disorders in the United States.
A single parathyroid adenoma is the cause of PHPT in
85% of cases.1 Traditionally, bilateral neck exploration
with excision of hyperfunctioning parathyroid glands
has been the standard in treatment of hyperparathyroid-
From the Division of Endocrine and Oncologic Surgery, Department
of Surgery (R.A., S.N., A.A., E.K.), and Section of Surgical Pathology and
Cytopathology, Department of Pathology (K.M.), Tulane University School
of Medicine, New Orleans, Louisiana, U.S.A.
Editor’s Note: This Manuscript was accepted for publication
October 10, 2012.
Presented at the 8th International Conference on Head and Neck
Cancer, Toronto, Ontario, Canada, July 21–25, 2012.
The authors have no funding, financial relationships, or conflicts
of interest to disclose.
Send correspondence to Emad Kandil, MD, Edward G. Schlieder
Chair in Surgical Oncology, Assistant Professor of Surgery, Otolaryngology and Medicine, Chief, Endocrine Surgery Section, Department of
Surgery, Tulane University School of Medicine, 1430 Tulane Ave., New
Orleans, LA 70124. E-mail: ekandil@tulane.edu
DOI: 10.1002/lary.23863
Laryngoscope 123: May 2013
1310
ism. However, in 2% to 7% of cases, surgery is not
curative at first operation, even by an experienced surgeon, and requires another surgery.2–4
Reoperations are technically difficult due to dense
scarring and tissue distortion after a previous cervical
operation. There is also a higher total complication rate
(8.3%–13%) and risk of injury to the recurrent laryngeal
nerve (0.8%–6.6%) with these reoperative surgeries.5,6
Preoperative localization of the remaining hyperfunctioning parathyroid glands in patients with previous
cervical operations is helpful in minimizing surgical
effort and complication rates during reoperation.7–9
Recent studies have shown multiple benefits to targeted parathyroidectomy for patients with PHPT. These
include less postoperative pain, decreased need for analgesia, a lower incidence of postoperative hypocalcaemia,
shorter operative times, and better cosmesis.10,11
Currently, ultrasonography and sestamibi scan are
the most popular methods used to locate the culprit
parathyroid gland in reoperative settings.12,13 One of the
major limitations of these imaging studies is the high
rate of false positives caused by other cervical pathologies and undergoing a previous surgery.14
Abdelghani et al.: PTH FNA Washout in Hyperparathyroid Patients
One of the newest adjuncts to parathyroid surgery
is fine-needle aspiration (FNA) with parathyroid washout. This method has been used to confirm or deny if the
tissue being sampled is of parathyroid origin.15–17 There
are very few studies with small numbers of patients that
have shown the use of preoperative FNA to localize
parathyroid adenomas and determine the eligibility of
patients for minimally invasive thyroid surgery with a
high sensitivity (94%), specificity (100%), and positive
predictive value (PPV) (100%).16,17
We aimed to study the diagnostic value of the parathyroid hormone (PTH) concentration found in the
needle washout of FNA performed preoperatively in
comparison to cytological evaluation of suspicious lesions
that were suggestive of enlarged parathyroid glands in
patients with recurrent or persistent PHPT.
TABLE I.
Demographics and Biochemical Features of the Patients (n 5 24).
Mean 6 SD
Range
Age (yr)
56 6 12
30–80
Female
87.5%
10.21 6 1.18
7.5 12.6
8.84 6 0.92
6.7 10.2
Serum calcium 6 months
postoperative (mg/dL)
9.23 6 1.07
8.7 10.4
Serum albumin (g/dL)
Serum PTH preoperative
(pg/mL)
Serum PTH postoperative
(pg/mL)
PTH washout (pg/mL)
3.86 6 0.57
2.6 4.5
111.5 6 106.25
31 356
45.1 6 21.3
5 74
4,393.2 6 1,074.8
743 17,413
PTH ¼ parathyroid hormone; SD ¼ standard deviation.
MATERIALS AND METHODS
A retrospective analysis of our endocrine surgery
database was performed. Between April 2009 and September 2011, all consecutive patients with recurrent or
persistent PHPT referred to a single surgeon were evaluated. The biochemical diagnosis of PHPT was arrived at
through standardized criteria. Before the washout was
preformed, PTH, thyroid-stimulating hormone, free thyroxin, and total calcium were evaluated in all patients.
Written informed consent was obtained from all patients.
In all patients, comprehensive ultrasound examination of
the neck was performed by the same operating surgeon.
This was compared with other imaging studies, including
computed tomography scan, when available.
FNA was done under ultrasound guidance on all
patients with nodular lesions suspected of being
enlarged parathyroid tissue. A 25-gauge needle was
used for the FNA as we and others have described
before.18–20 After insertion of the needle, negative pressure was applied to the suspicious lesion. Aspirated
material was smeared on glass slides for cytologic examination, and then the needle was washed out with 2 mL
of 0.9% normal saline. The cell block for immunohistochemical staining was performed whenever possible. The
cytopathology report is usually available 1 to 2 days after the biopsy compared to several days for the PTH
washout results. Nonetheless, the cytopathologist was
blinded to the PTH washout results. The resulting supernatant was the source of our measured PTH
concentrations. A positive cutoff value for the PTH
washout was defined as being superior to the patient’s
serum PTH level at the time of sampling. It was later
compared to the washout results when they became
available. We routinely performed intraoperative PTH
level monitoring in all cases.
Sensitivities of the cytology and the PTH washout
were calculated. We used the Fisher exact test to compare the two sensitivities. The analysis was generated
using SAS software version 9.3 for Windows (SAS Institute Inc., Cary, NC). The results were considered
statistically significant if the two-tailed P value was
<.05. All values are expressed as mean 6 standard deviation, range, or absolute number.
Laryngoscope 123: May 2013
—
Serum calcium
preoperative (mg/dL)
Serum calcium 1 week
postoperative (mg/dL)
RESULTS
The study consisted of 24 consecutive patients. All
patients had a history of prior neck exploration for PHPT,
with persistent (n ¼ 17) or recurrent (n ¼ 7) hyperparathyroidism after the initial procedure. The average age of
the patients was 55 6 12 years, with the majority of the
patients being female (87.5%). The mean preoperative serum PTH level was 111.5 6 106.25 pg/mL (normal: 15–65
pg/mL). The average preoperative serum calcium level
was 10.8 6 0.5 mg/dL (normal: 8.6–10.2 mg/dL). The
mean PTH washout level was 4393 6 1074.8 pg/mL and
ranged from 743 to 17413 pg/mL. The demographic and
biochemical features of the patients are shown in Table I.
The parathyroid lesions were identified by surgeonperformed ultrasound in all 24 patients. Parathyroid adenoma was found in 19 patients (79.1%), and five
(20.8%) patients were found to have parathyroid hyperplasia requiring removal of additional parathyroid
glands. After identifying the hyperplastic parathyroid
glands, resection was performed with the goal of leaving
the smallest parathyroid gland. We believe that routine
intraoperative PTH monitoring is essential in identifying
these patients with hyperplasia. However, the aim of the
current study was to compare the diagnostic value of cytology of FNA of suspicious lesions to needle washout for
PTH levels. Therefore, this did not change the accuracy
of the washout in identifying the culprit lesion. Twentytwo patients had an elevated PTH washout concentration showing a PPV of 100%. Cytologic examination
detected parathyroid cells in seven patients (29%). The
remaining 17 negative cytological results consisted of
nine (53%) follicular cell specimens and eight (47%) with
a nondiagnostic or suboptimal result. We believe the reason for finding these follicular cells is due to the needle
passing through the thyroid to get access to the parathyroid gland located posterior to the thyroid gland. The
sensitivity of cytological examination for finding the culprit parathyroid adenoma was 29% versus 91.6% with a
PPV of 100% for PTH washout (P < .001). Four (16.6%)
of the cases had confirmatory immunostaining
Abdelghani et al.: PTH FNA Washout in Hyperparathyroid Patients
1311
performed that revealed parathyroid cells staining with
parathormone and chromogranin antibodies (Fig. 1).
Preoperative sestamibi scans detected parathyroid adenoma in this select group in only nine patients (37.5%).
The FNA procedure was well tolerated by all
patients. There was no pain at the site of the wound,
and there were no episodes of seroma or hemorrhaging.
Table II shows the sensitivity of the PTH washout
compared to that of cytology.
The average patient follow-up time was 3.5 6 4.2
months and ranged from 9 days to 11 months. During
follow-up, all patients were normocalcemic, with an average PTH value of 57 6 34.5 pg/mL and an average
calcium level of 8.84 6 0.92 mg/dL, postoperatively. At
the 6-month mark, the average calcium level for the
patients in the study was 9.23 6 1.07 mg/dL.
DISCUSSION
Targeted parathyroidectomy has many advantages
over other conventional methods.19 The success rate of
targeted parathyroidectomy depends on accurately localizing the hyperfunctioning gland. Some popular
localizing techniques currently are ultrasound, sestamibi
scan, and parathyroid hormone washout.
Ultrasound is easily available and performed in an
office-based setting. Also, ultrasound allows for real-time
visualization of the needle in relation to the lesion.21 On
the other hand, ultrasound has a sensitivity of 72% to
85% in detecting parathyroid lesions22–24 and can be the
only adjunct needed for a select group of patients with
PHPT.25 Nonetheless, normal parathyroid glands are still
rarely visible on ultrasound, depending on the skill of the
person performing the ultrasound. In addition, ultrasound can show false positives secondary to thyroid
pathology, blood vessels, lateral cervical lymph nodes, or
the esophagus. False negatives found on ultrasound could
be caused by an atypically located parathyroid gland.26
Sestamibi scan is widely used in preoperative localization of parathyroid adenomas. Sestamibi scan is
especially useful in isolated and ectopic adenomas rather
than in multiple adenomas.27 False negative results are
due to the small size, site, and histological characteristics of such lesions.28
TABLE II.
Sensitivity of PTH Washout Compared to Sensitivity of Cytology.
No. of
Patients
True
Positive
False
Negative
Sensitivity
P Value
<.001*
Cytology
24
7
17
29%
PTH washout
24
22
2
91.6%
*P value was calculated from Fisher exact tests.
PTH ¼ parathyroid hormone.
Our data show 29% of FNA biopsies had cytologic
specimens indicative of parathyroid tissue that were
later confirmed by surgical pathology. The results of our
cohort compel us to agree with the opinion that the low
sensitivity of cytological diagnosis decreases the reliability of this method for preoperative confirmation.29,30
PTH washout is an accurate way to localize culprit
lesions in patients with findings indicating parathyroid
lesions on neck ultrasound. Frasoldati and colleagues
showed that a PTH washout result of more than 101 pg/mL
had a 100% sensitivity and specificity for verification of
parathyroid tissue.31 Marcocci and colleagues regarded a
PTH washout value of >50 pg/mL as positive for sampling
in parathyroid tissue,32 whereas Maser and colleagues
reported that a PTH washout value of >1,000 pg/mL indicates sampling of parathyroid tissue.33 Sacks and
colleagues reported 45 patients with PHPT who underwent
FNA of suspected parathyroid adenomas. Thirty-seven of
the 45 patients had elevated PTH levels, with a specificity
of 100% at the time of operation.34 These results are consistent with our own. However, it is important to note that the
PTH values from different assays are not interchangeable.
Our data show that a PTH washout value above the
serum PTH level is a valid indication that hyperfunctioning
parathyroid tissue was sampled. A PTH washout value
higher than the serum PTH should be considered diagnostic in localizing the parathyroid due to the hormone
dilution in the FNA. One must consider that the aspirate is
rinsed and diluted before being measured. Given this, the
measured PTH level of the aspirate most likely corresponds
to a much higher concentration in the original sample.32
Because a cutoff is needed, we used any value higher than
the serum PTH as our cutoff point, signifying the sample
was parathyroid tissue. Our data concluded that a parathyroid FNA value over the patient’s serum PTH level
indicated a hyperfunctioning parathyroid was sampled.
Further studies with larger numbers at different institutions are needed to determine the PTH FNA cutoff value
required to confirm a hyperfunctioning parathyroid lesion.
CONCLUSION
Fig. 1. Parathyroid cells stained with parathormone and chromogranin antibodies. [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]
Laryngoscope 123: May 2013
1312
Our study confirms the high reliability of parathyroid FNA washout in locating hyperfunctioning
parathyroid tissue when the results are of a greater
value than the serum PTH level. Considering its low
sensitivity, cytomorphology alone is not sufficient to confirm a parathyroid lesion. PTH washouts can contribute
significantly in establishing the parathyroid nature of
cervical lesions. With its high specificity, an FNA with
washout should be considered to confirm abnormal
Abdelghani et al.: PTH FNA Washout in Hyperparathyroid Patients
ultrasound findings in patients who underwent an
unsuccessful parathyroidectomy.
17.
18.
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