Neuroradiolog y / Head and Neck Imaging • Original Research

Johnson et al.
Sonography of Cystic Parathyroid Adenoma

Neuroradiology/Head and Neck Imaging

Original Research

Cystic Parathyroid Adenoma:

Sonographic Features and
Correlation With 99mTc-Sestamibi
SPECT Findings
Nathan A. Johnson1 OBJECTIVE. The purpose of this study was to describe the typical ultrasound features
Linwah Yip 2 of cystic parathyroid adenoma.
Mitchell E. Tublin1 MATERIALS AND METHODS. A review of a surgical database and electronic medi-
cal records from 2006 to 2009 identified the cases of 15 patients who underwent preoperative
Johnson NA, Yip L, Tublin ME cervical sonography for primary hyperparathyroidism with subsequent resection of patholog-
ically proven parathyroid adenoma with predominantly cystic components. Two radiologists
retrospectively evaluated the preoperative ultrasound images and assessed for cyst complexi-
American Journal of Roentgenology 2010.195:1385-1390.

ty, size, location, and color Doppler vascularity. Technetium-99m-sestamibi SPECT findings,
surgical and pathologic reports, and the results of parathyroid hormone assay of the cyst fluid
also were reviewed.
RESULTS. Most of the cystic adenomas (14/15, 93%) were deep or inferolateral to the ad-
jacent thyroid. The same percentage were elongated and had peripheral nodular components.
An echogenic border separating the adenoma from the overlying thyroid was identified in 9
of 15 patients (60%). Color Doppler examination of 14 patients showed feeding vessels with
internal color flow to the solid components in 10 patients (71%). Six of 14 patients underwent
preoperative or intraoperative sampling of cyst fluid, and the assay showed the parathyroid
hormone levels ranged from 1,198 to greater than 5,000 pg/mL. Fourteen of 15 patients un-
derwent preoperative sestamibi SPECT, and the adenoma was definitively localized in four
patients (29%). The accuracy of preoperative localization improved to 79% (11/14) when ses-
tamibi SPECT scans were interpreted in correlation with cervical ultrasound images.
CONCLUSION. Awareness of typical sonographic features (location, color Doppler
vascularity) may aid radiologists in preoperative localization of parathyroid adenomas, even
when cystic degeneration occurs. In cases in which imaging or clinical features are equivocal,
the results of cyst fluid sampling and parathyroid hormone assay are confirmatory.

Keywords: hyperparathyroidism, parathyroid adenoma,
parathyroid cyst, ultrasound
DOI:10.2214/AJR.10.4472
Received February 23, 2010; accepted after revision
May 10, 2010.
1
Department of Radiology, Division of Abdominal
Imaging, University of Pittsburgh School of Medicine,
200 Lothrop St., Presbyterian South Tower, Ste. 3950,
Pittsburgh, PA 15213. Address correspondence to
N. A. Johnson (johnsonna2@upmc.edu).
2
Section of Endocrine Surgery, University of Pittsburgh
School of Medicine, Pittsburgh, PA.
AJR 2010; 195:1385–1390
0361–803X/10/1956–1385
© American Roentgen Ray Society
C
ystic degeneration of parathyroid
adenoma is seen in approximate-
ly 4% of abnormal parathyroid
glands [1] and 1–2% of patients
with primary hyperparathyroidism [2, 3]. Al-
though the cystic appearance can confound
the accurate diagnosis of parathyroid adeno-
ma for imagers not familiar with the much
less common cystic variety (particularly of
lesions that may be nearly entirely cystic),
cystic parathyroid adenoma is not a distinct
histopathologic diagnosis but is an uncom-
mon feature of parathyroid adenoma. As
such, the clinical manifestations of functional
cystic parathyroid adenoma usually are simi-
lar to those of nondegenerated adenomas and
include a biochemical profile consistent with
that of primary hyperparathyroidism and a
broad array of symptoms, including fatigue,
depression, nephrolithiasis, osteoporosis, and
abdominal pain. As have their solid counter-
parts, cystic adenomas have been reported to
occur in hypercalcemic crisis as the result of
acute necrosis or hemorrhage of a parathy-
roid adenoma [4].
The sonographic features of parathyroid
adenoma and the utility of cervical ultra-
sound in the preoperative evaluation of pa-
tients with primary hyperparathyroidism
have been well documented [5–7]. Howev-
er, descriptions of the relevance, cause, and
imaging appearance of cystic adenoma have
been limited to sporadic case reports and
small surgical series, there being few reports
of this entity in the radiology literature [1–
4, 8–12]. Greater use of cervical sonography
for assessment of thyroid nodules and local-
ization of parathyroid adenoma has made it

AJR:195, December 2010 1385


imperative that radiologists recognize the sa-
lient ultrasound features of cystic adenoma.
To identify the typical imaging characteris-
tics of cystic adenoma, we studied the sono-
graphic and scintigraphic features of 15 his-
tologically proven cystic adenomas.
Materials and Methods
Patient Sample
A retrospective review of an endocrine surgical
database and electronic medical records at a sin-
gle institution was performed. The clinical data-
base consisted of 726 patients who underwent ex-
ploration for primary hyperparathyroidism from
August 2006 through February 2009. A total of
15 patients with biochemically and histologically
confirmed parathyroid adenoma and preoperative
cervical sonograms showing predominantly cystic
adenoma were ultimately identified from this da-
tabase. Only patients found to have predominant-
ly cystic lesions (> 50% of the estimated volume
American Journal of Roentgenology 2010.195:1385-1390.
based on available preoperative images) were in-
cluded because small cystic elements within pre-
dominantly solid adenomas are unlikely to con-
found imaging or clinical diagnoses. This arbitrary
definition of cystic lesions was used in our series
to focus on lesions with an imaging appearance
less commonly encountered; precise quantifica-
tion of the cystic component was not attempted.
Although cystic components can be a pathologic
feature of parathyroid adenoma, the proportion of
any cystic component is not used as a diagnostic
criterion for the histopathologic diagnosis of para-
thyroid adenoma.
Cervical Sonography
Cervical ultrasound examinations performed for
parathyroid localization included representative im-
ages of the thyroid and potentially abnormal para-
thyroid glands. Sonographers initially obtained im-
ages using a Logiq 9 platform (GE Healthcare) and
a 12-MHz linear array probe. The supervising radi-
ologist reviewed the preliminary ultrasound find-
ings and pertinent clinical and laboratory data and
then scanned each patient to confirm the presence
of any suspected abnormalities and to identify ab-
normal parathyroid adenomas if the preliminary
search by the sonographer was unsuccessful.
Cervical ultrasound studies were retrospectively
reviewed in collaboration by two radiologists with
fellowship training in abdominal imaging who rou-
tinely perform cervical ultrasound in clinical prac-
tice. The size and location of the cystic adenomas
were tabulated. The morphologic features and vas-
cularity of the lesion at color Doppler examina-
tion were qualitatively assessed. The lesions were
classified morphologically as simple cysts or com-
plex cysts as defined by the presence of peripheral
1386 AJR:195, December 2010
Johnson et al.
nodularity or thickened internal septations. Lesion
vascularity was categorized by the presence of an
identifiable feeding vessel with internal color flow
or the absence of internal color flow.
Sestamibi SPECT
Technetium-99m-sestamibi SPECT was per-
formed 10 minutes and 3 hours after IV injection
of 25 mCi 99mTc. SPECT was performed with a du-
al-head camera (DST-Xli, SMV) and a low-ener-
gy high-resolution collimator. Each session lasted
approximately 30 minutes. SPECT images (128 ×
128 matrix) were reconstructed to produce 3D pro-
jections on which early and delayed images were
viewed simultaneously. Focally increased uptake
on either the early or the delayed images separate
from the thyroid uptake was considered diagnos-
tic of an abnormal parathyroid gland. All sestami-
bi SPECT studies were retrospectively interpreted
by the same two radiologists, who were initially
blinded to the anatomic location of the lesion and
then used the ultrasound images for anatomic cor-
relation of the scintigraphic findings. Sestamibi
SPECT studies were graded as negative (no local-
ization with scintigraphy), equivocal (initial local-
ization with scintigraphy alone not definitive, al-
though comparison with ultrasound suggested a
scintigraphic correlate), of definitive (clear scinti-
graphic localization that corresponded in anatomic
location to the cystic parathyroid adenoma).
Results
Demographics
Cystic adenomas were identified in 15 pa-
tients (nine women, six men; mean age, 58
years; range, 40–80 years). Thirteen of the
15 patients had elevated levels of serum para-
thyroid hormone (PTH) (mean, 277 pg/mL;
range, 77–1,027 pg/mL) and calcium (mean,
11.5 mg/dL; range, 10.3–13.1 mg/dL) and
had symptoms consistent with sporadic pri-
mary hyperparathyroidism. One of the other
two patients had multiple endocrine neopla-
sia and presented with recurrent hyperpara-
thyroidism, having 25 years previously un-
dergone cervical exploration and subtotal
parathyroidectomy. The other patient was
previously thought to have a cystic thyroid
nodule, which recurred despite several per-
cutaneous aspirations. Mild but symptomat-
ic primary hyperparathyroidism was eventu-
ally diagnosed, and the cystic adenoma was
resected. One patient had a double adeno-
ma with a second, contralateral small solid
parathyroid adenoma discovered after four-
gland parathyroid exploration was undertak-
en when the intraoperative PTH level did not
normalize after resection of the cystic adeno-
ma. After 6 months or more of follow-up, 14
patients had normal serum PTH levels asso-
ciated with normocalcemia, and one patient
was lost to follow-up.
Cervical Sonography
All cystic adenomas were in typical an-
atomic locations deep to the mid or lower
poles of the thyroid (nine superior, six inferi-
or). Most of the adenomas (13/15, 87%) were
oblong with the largest dimension in the cran-
iocaudal dimension (Fig. 1). The mean cran-
iocaudal dimension was 3.4 (SD, 1.0) cm, an-
teroposterior dimension was 1.9 (SD, 0.7) cm,
and transverse dimension was 2.0 (SD, 0.8)
cm. In 14 of 15 patients (93%), a complex cys-
tic lesion with peripheral nodularity and thick
internal septations was identified at preopera-
tive sonography (Fig. 2). The other lesion was
entirely cystic with no peripheral nodularity
or internal septations. An extrathyroidal ori-
gin was suggested by a position deep (11/15,
73%) or inferolateral (3/15, 20%) to the ipsi-
lateral thyroid lobe (Fig. 3). One lesion de-
formed the posterior border of the overlying
thyroid lobe such that the center appeared
within the thyroid parenchyma (Figs. 3C and
3D). An echogenic border separating the ad-
enoma from the overlying thyroid was seen
in nine of 15 patients (60%) (Figs. 3A and
3B). Color Doppler examination revealed a
prominent feeding vessel with internal col-
or flow to the solid components of the lesion
in 10 of 14 patients (71%) (Fig. 4). Minimal
to no discernible color Doppler flow or well-
defined feeding vessel was found in four pa-
Fig. 1—41-year-old woman with left superior cystic
parathyroid adenoma. Sagittal ultrasound image
of thyroid gland shows typical location of superior
parathyroid gland deep to midpole of left thyroid lobe
and elongated shape. As are their solid counterparts,
cystic parathyroid adenomas usually are elongated
along craniocaudal axis. Distinct echogenic border
(arrow) separates adenoma from overlying thyroid
lobe.
 Sonography of Cystic Parathyroid Adenoma

A B C
Fig. 2—Complex cystic morphologic findings.
A, 56-year-old woman with right inferior cystic adenoma. Sagittal ultrasound
image shows extrathyroidal nodule with typical complex cystic structure that
includes peripheral nodular component.
B, 57-year-old woman with right superior cystic adenoma. Sagittal ultrasound
image shows elongated complex cystic nodule deep to thyroid parenchyma.
C and D, 40-year-old man with large left inferior cystic adenoma. Sagittal
ultrasound image (C) shows complex cystic lesion with peripheral nodular
component. Axial contrast-enhanced CT scan of neck (D) shows marked
enhancement of peripheral nodule (arrow) reflecting functional parathyroid
American Journal of Roentgenology 2010.195:1385-1390.

tissue within this large cystic lesion.

tients (29%), and one patient did not undergo
color Doppler examination.
Six of the 15 lesions (40%) were aspirat-
ed either preoperatively under ultrasound
guidance or intraoperatively. The PTH level
was greater than 1,000 pg/mL for all lesions
(range, 1,198 to > 5,000 pg/mL). The demo-
graphic and imaging features for our patient
sample are summarized in Table 1.
Dual-Phase Sestamibi Scintigraphy
Fourteen of 15 patients (93%) underwent
preoperative sestamibi SPECT in addition to
cervical ultrasound. At retrospective review,
four studies (29%) were classified as defini-
tive, seven as equivocal (50%), and three as
negative (21%) (Table 1).
Discussion
Cystic parathyroid adenoma, or function-
al parathyroid cyst, accounts for a small pro-
portion (1–4%) of all parathyroid adenomas
[1–3]. Much of the literature on parathyroid
cysts categorizes these lesions into function-
al and nonfunctional (true) parathyroid cysts
on the basis of the presence or absence of el-
evated serum PTH levels. The pathogenesis
is hypothesized to be distinct for these two
entities: Cystic adenomas result from hem-
orrhage or cystic degeneration of a parathy-
roid adenoma, and nonfunctional parathy-
roid cysts may originate from embryologic
remnants or the coalescence of microcysts or
occur as the result of abnormal retention of
PTH [13].
Functional parathyroid cysts commonly
become evident with symptoms of primary
hyperparathyroidism (fatigue, depression,
osteoporosis, nephrolithiasis), and nonfunc-
tional cysts become evident as symptoms re-
lated to local mass effect (dysphagia, dysp-
nea, hoarseness) or are incidental findings.
The relative proportion of functional and
nonfunctional parathyroid cysts in previ-
ous series has varied markedly, functional
cysts accounting for 10–90% of all parathy-
roid cysts [3, 4, 14]. In a previous surgical
series from a subspecialty endocrine surgery
practice [3], functional parathyroid cysts ac-
counted for approximately 85% of all resect-
ed parathyroid cysts, probably because pa-
tients with primary hyperparathyroidism are
referred to endocrine surgeons.
Whether or not they are functional, all
parathyroid cysts have elevated levels of
PTH in the cyst fluid. Previous reports have
suggested that nonfunctional cysts tend to be
unilocular and contain clear fluid and that
functional cysts have more complex cystic
features and often contain cloudy brown flu-
id suggesting previous hemorrhage [2, 4, 12,
14, 15]. This gross appearance supports the
theory that most functional parathyroid cysts
originate from hemorrhage and cystic degen-
eration of parathyroid adenomas.
Previous descriptions of the imaging ap-
pearance of cystic adenomas are primarily
limited to case reports and small case series
in the radiologic literature. Many of these de-
scriptions predate the use of state-of-the-art
high-resolution ultrasound and color Dop-
pler imaging. Some contemporary and larg-
er series of parathyroid adenomas included
cystic lesions. In a 1987 report, Randel et al.
[1] described cystic changes, defined as one
or more cystic areas with increased through
transmission at ultrasound examination, in
nine of 235 consecutively examined abnor-
mal parathyroid glands. Reading et al. [16]
in 1982 reported that “several” parathyroid
glands in a series of 165 consecutively ex-
amined patients had cystic components, but
those investigators did not further describe
the imaging characteristics.
In our series, cystic adenomas had several
sonographic features in common with their
solid counterparts. All but one were clearly
separate from the adjacent thyroid and had
an extrathyroidal origin suggested by loca-
tion or a well-defined echogenic tissue plane

AJR:195, December 2010 1387


A B
American Journal of Roentgenology 2010.195:1385-1390.
C D
A B
separating the adenoma from the thyroid pa-
renchyma. In addition, at ultrasound exami-
nation, all but one cystic adenoma was ob-
long with the greatest dimension along the
craniocaudal axis, which is the usual orien-
tation of enlarged parathyroid glands. All
but one cystic adenoma also had an eccentric
solid nodular component.
The mean size of cystic adenomas in our
series (3.4 × 1.9 × 2.0 cm) was substantially
larger than that of a typical solid adenoma,
which commonly measures approximately 1
cm [6]. Thus a size greater than commonly
seen for solid adenomas should not dissuade
the radiologist from considering the diagno-
sis of cystic adenoma in the appropriate clin-
ical setting. As in the case of noncystic para-
thyroid adenoma, color Doppler examination
was a helpful adjunct technique for confirm-
1388 AJR:195, December 2010
Johnson et al.
ing the presence of a prominent feeding ves-
sel supplying the solid portion of the nodule
[17]. The echogenic tissue plane separating
the parathyroid gland from the adjacent thy-
roid and the presence of a polar feeding ves-
sel are two features that aid in differentiating
cystic adenomas from cystic thyroid nodules.
In equivocal cases, PTH assay after ultra-
sound-guided cyst aspiration shows marked
elevation of PTH level, which is diagnostic
of parathyroid origin.
The reported accuracy of preoperative
localization of noncystic parathyroid ade-
nomas with sestamibi SPECT varies wide-
ly in the literature, the reported sensitiv-
ity ranging from 68% to 95% [6]. Little is
known about the diagnostic accuracy of ses-
tamibi SPECT in evaluation for cystic ade-
noma. In a series of seven parathyroid cysts,
Fig. 3—Differentiation of cystic parathyroid adenoma
from thyroid nodule.
A, 61-year-old woman with left superior cystic
adenoma. Sagittal ultrasound image shows distinct
echogenic border (arrows) between cystic lesion and
overlying thyroid.
B, 51-year-old woman with left superior cystic
adenoma. Transverse ultrasound image shows
discrete echogenic border separating cystic
adenoma from overlying thyroid (arrows).
C and D, 71-year-old woman with right superior
cystic adenoma. Transverse (C) and sagittal (D)
ultrasound images of right thyroid lobe show complex
nodule that appears centered in right thyroid lobe
with no echogenic border between cystic adenoma
and thyroid. In these cases, cyst aspiration for
parathyroid hormone assay may be necessary to
differentiate parathyroid lesion from complex thyroid
nodule.
Fig. 4—Color Doppler findings.
A, 61-year-old woman with left superior cystic
parathyroid adenoma. Color Doppler image shows
prominent feeding vessel (arrow) and color flow
within solid components.
B, 56-year-old woman with right inferior parathyroid
adenoma. Color Doppler image of adenoma shows
another example of flow within solid portions of
nodule and feeding vessel (arrow).
an association with a cold defect was seen
on sestamibi SPECT images [12]; we made
this finding in one patient with a large, pre-
dominantly cystic adenoma. In a series of 37
cystic adenomas reported in 2009 [3], 25 of
37 of the adenomas (68%) were correctly lat-
eralized with preoperative sestamibi SPECT.
Although the small sample size in our series
does not allow definitive characterization of
the diagnostic accuracy of sestamibi SPECT
in patients with cystic adenomas, only a small
number of lesions (4/14, 29%) were definitive-
ly localized with scintigraphy alone. Howev-
er, an additional 7 of 14 patients (50%) had
scintigraphic findings that correlated with
the ultrasound findings, highlighting the im-
portance of concurrent preoperative cervical
ultrasound for parathyroid localization, even
of cystic adenoma (Fig. 5).
 Sonography of Cystic Parathyroid Adenoma

We chose to focus exclusively on func- sonographer may have to determine whether thyroid adenoma as a thyroid nodule or other
tional cystic adenomas because of the crucial a cystic neck lesion is a parathyroid adeno- cystic neck lesion can lead to more-invasive
role the sonographer may play in preopera- ma, cystic thyroid nodule, or other rare cystic surgery (e.g., four gland parathyroid explora-
tive identification of these rare lesions. The neck lesion. The misdiagnosis of cystic para- tion versus minimally invasive parathyroidec-
tomy) or delay in treatment if the parathyroid
TABLE 1:  Imaging Characteristics of Cystic Parathyroid Adenoma (n = 15) adenoma is dismissed as a thyroid cyst. The
Characteristic Value % preoperative diagnosis of parathyroid cyst
Location also is critical to guiding the operative ap-
proach to avoid cyst rupture and prevent sub-
Superior 9 (5 right, 4 left) 60
sequent parathyromatosis. For nonfunction-
Inferior 6 (3 right, 3 left) 40 al parathyroid cysts, which are usually large
Position in relation to thyroid simple epithelial cysts, the sonographic fea-
Deep 11 73 tures are unlikely to add much specificity to
Inferolateral 3 20 the diagnosis. The primary role of ultrasound
in these cases is to guide cyst aspiration for
Intrathyroidal 1 7
PTH assay to confirm parathyroid origin and
Echogenic border with thyroid 9 60 potentially for therapeutic intervention.
Mean dimension (cm) Less common entities to be considered in
Craniocaudal 3.4 (SD, 1.0) the differential diagnosis of cystic neck le-
Anteroposterior 1.9 (SD, 0.7) sions encountered in the typical locations of
the parathyroid glands include nodal meta-
Transverse 2.0 (SD, 0.8)
American Journal of Roentgenology 2010.195:1385-1390.

static lesions that can typically appear cys-

Morphologic characteristics tic (e.g., lymphoma, squamous cell carcino-
Complex cyst 14 93 ma, papillary thyroid cancer) and cervical
Simple cyst 1 7 thymic cysts. The typical locations of other
Color Doppler finding cystic neck masses, such as second branchial
cleft cysts (anterior to the sternocleidomas-
Examination not performed 1
toid muscle near the angle of the mandible)
Feeding vessel with flow to solid components 10 71 and thyroglossal duct cysts (suprathyroidal
No discernible Doppler flow 4 29 midline lesion embedded in strap muscles),
Sestamibi SPECT localization can suggest the diagnosis, but prospective
Examination not performed 1 definitive differentiation of these rare le-
sions on the basis of sonographic appearance
Definitive 4 29
and location alone may not be possible [13].
Equivocal 7 50 When parathyroid origin is suspected, cyst
Negative 3 21 aspiration for PTH assay is a safe and spe-
Note—Except for dimensions, values are number of lesions. cific method of confirmation.

A B C
Fig. 5—50-year-old woman with left inferior cystic parathyroid adenoma.
A, Early 3D sestamibi SPECT image of neck shows asymmetric uptake in inferior aspect of left thyroid lobe (arrow). Early uptake in adenoma in inferior position or
asymmetry of thyroid can account for this finding.
B, Delayed 3D sestamibi SPECT image shows no corresponding focus of radiotracer retention in this region.
C, Sagittal sonographic image of inferior aspect of left thyroid lobe shows complex cystic nodule in same location as asymmetric radiotracer uptake in A and illustrates
usefulness of correlation between functional and anatomic imaging techniques.

AJR:195, December 2010 1389

 Johnson et al.

One limitation of our study was that our
observations were retrospective, precluding
determination of the sensitivity and speci-
ficity of our imaging findings and discrim-
ination between cystic adenomas and other
cystic neck lesions. As our experience with
routine preoperative ultrasound for parathy-
roid localization continues to increase, the
usefulness of sonographic characteristics for
prospective discrimination between cystic
parathyroid lesions and other cystic lesions
will be the focus of study.
Cystic parathyroid adenoma has a typical
sonographic appearance and imaging fea-
tures in common with noncystic adenoma,
which can aid the sonographer in accurate di-
agnosis. Awareness of this entity may prompt
correlation with clinical and biochemical evi-
dence of primary hyperparathyroidism when
a cystic neck mass that has these features is
encountered. Ultrasound-guided aspiration
American Journal of Roentgenology 2010.195:1385-1390.
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1390 AJR:195, December 2010