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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1382_Библиотеки_им_академика_М_И_Перельмана.pdf
240
ENDOCRINE SURGERY
Fig. 17.7. Protocol: injection of 12 MBq of
acquisition at T + 3 (20 min acquisition), SPECT at T + 45 min (30 s/projection). For SPECT, image was acquired with a 20% window
centered over the 140-keV photopeak. Planar pinhole (A:
parathyroid adenomas. The posterior extension of the adenoma on SPECT images is highly suggestive of P4 origin, despite its
apparent right inferior origin on planar images (white arrow).
Discrepancies between studies could be
related to several factors including differences
123
I at T-2 h, injection of 740 of
99m
Tc-sestamibi, B:
uniglandular disease is greater than 95% [25,
31, 32].
in imaging protocols (including radiopharmaceuticals used, tracer activities, collimators
used, delays for image acquisitions, and interpretation criteria) and patient selection (goiter,
gland weights, and PTH values).
As parathyroid scintigraphy is often used to
direct focused surgical approaches, the results
should be evaluated in relation to the surgeon’s
choice of operative procedure (adapted versus
nonadapted to the parathyroid disease). A study
showing only a single parathyroid lesion in a
results is the solid benign thyroid nodule, either
solitary or as part of a multiglandular gland.
Therefore the specificity of parathyroid scintigraphy is highly dependent upon the patient
population. Subtraction images, late
sestamibi delayed acquisitions (2–3 h), and
SPECT should improve specificity. Other potential false-positive findings are related to thyroid
carcinomas, thymomas, and metastatic or inflam-
matory lymph nodes.
patient with double hyperfunctioning adenomas
should be interpreted as a false-positive result
because it should lead to a nonadapted focused
surgical approach with a subsequent surgical
conversion. By contrast, a negative study in the
presence of MGD results in adapted bilateral
open-surgery and should be interpreted as truenegative study for parathyroid adenoma.
Using these modified criteria, the positive
predictive value of scintigraphy for identifying
parathyroid lesions, cystic adenomas (after
necrosis or cystic degeneration), and hyperplas-
tic glands in cases of sporadic or familial MGDs.
The incidence of MGD is about 20% when para-
thyroid scintigraphy is negative compared with
1–2% when scintigraphy is positive for a single
adenoma [32]. The reduced sensitivity for
detecting MGD is not clearly understood and
does not seem to be entirely related to lower
99m
Tc-sestaMIBI at T0, dual tracer planar pinhole
123
I, C: subtraction images) and SPECT images (D)of
The most common cause of false-positive
99m
Tc-
False-negative results are attributed to small
241
PARATHYROID LOCALIZATION AND IMAGING
Fig. 17.8. Parathyroid scintigraphy revealed a typical right P4 adenoma. (A)
images (axial, sagittal, and coronal imaging planes). Planar pinhole subtraction images reveal a focal moderate accumulation
99m
Tc-sestamibi located under the left thyroid lobe (C). SPECT images demonstrate that the gland is prolapsed behind the thyroid
of
99m
Tc-sestamibi, (B)
123
I, (C) subtraction, (D) SPECT
gland and is extended posteriorly (black arrows).
Fig. 17.9. Planar pinhole (A:
99m
Tc-sestamibi, B:
123
I, C: subtraction images) and SPECT images (D) of parathyroid adenomas.
Typical P3 adenoma which is located at the tip of the left inferior lobe on planar images and remains anterior on SPECT images.
242
ENDOCRINE SURGERY
Fig. 17.10. The
anterior image at 45 min postinjection. (B) 3D image of SPECT acquisition. (C) Orthogonal views (axial, sagittal, and coronal) of
SPECT.
gland weights. Negative results have been attributed to overexpression of sestamibi efflux proteins, fewer mitochondrial-rich oxyphil cells or
low active growth phase.
As in other imaging techniques true-negative
results correspond to misdiagnoses including
laboratory errors, secondary hyperparathormo-
99m
Tc-sestamibi scintigraphy shows a left large parathyroid adenoma extending into the mediastinum. (A) Planar
parathyroid glands are not visible on parathyroid scintigraphy.
Only a few studies have demonstrated the
role of SPECT acquisitions for improving the
localization of adenomas in patients operated through focused surgical approaches
[30, 33].
nemia related to vitamin D deficiency, false
hypercalcemia (hypergammaglobulinemia),
non-PTH 1-84 dependant hypercalcemia (paraneoplastic PTHrp secretion, bone metastases,
sarcoidosis, hyperthyroidism, drugs), and
familial hypocalciuric hypercalcemia. Normal
Computed Tomography
Computed tomography (CT) is a useful technique
for parathyroid localization because of its ability
to detect ectopic glands in anterior, middle, and
243
PARATHYROID LOCALIZATION AND IMAGING
Fig. 17.11. Examples of ectopic parathyroid adenomas. (A and B) P4-derived adenoma. (C and D) Intrathymic right P3-derived
adenoma. (E) P3-derived adenoma located in the aorto-pulmonary window (sagittal plane).
posterosuperior mediastinum. Most of these
glands are inaccessible for ultrasound. CT should
be done with thin cuts (3–5 mm). Nevertheless,
the limitations of CT remain related to the size of
the adenoma. Intravenous contrast material
should be used to obtain the best results because
many parathyroid adenomas will enhance. CT is
less effective in the neck than in the mediastinum.
It is useful for deep-seated retroesophageal glands
in the neck but less effective for parathyroid
glands close to the thyroid. Sparkler effects
observed from surgical clips used in prior
Fig. 17.12.
(sagittal, axial, and coronal imaging planes) help in the diagnosis of paraesophageal ectopic adenoma.
99m
Tc-sestamibi scintigraphy. (A) Planar images find a left inferior parathyroid adenoma. (B–D) SPECT images
244
ENDOCRINE SURGERY
operations, scanning artefacts resulting from
breathing and swallowing can makeinterpretation
of images more difficult. Lymph nodes and tortuous vessels can also be mistaken for enlarged
parathyroid glands. False-positive results are
more frequent than with other modalities and
rates may reach 50% [34]. The sensitivity reported
ranges from 16 to 70% [8, 12, 13, 35–44].
The use of 4-dimensional CT (4D-CT) for
parathyroid imaging has recently been reported
[45]. 4D-CT gives exquisitely detailed multiplanar images and allows the visualization of differences in the perfusion characteristics of
hyperfunctioning parathyroid glands compared
with normal glands and other structures. This
technique provides both anatomic and functional information in a single study, and seems
very promising.
CT imaging of the parathyroid glands is
relatively expensive, exposes the patient to
radiation, and requires the administration of
contrast medium. Nevertheless, CT is particularly useful for identifying mediastinal adenomas missed at initial surgery. However the high
rate of false-positive results means it must be
used in conjunction with a sestamibi scan. Once
the precise location in the mediastinum of
the missing gland is determined, the surgeon
can choose the best surgical approach.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) provides
excellent anatomic detail and is slightly more
sensitive than CT. It does not require intravenous contrast and is not subject to the ‘‘sparkler
effect’’ or shoulder artifact. Nevertheless, MRI is
expensive and patient compliance is sometimes
limited by claustrophobia.
Parathyroid adenomas typically have a low
signal intensity in T1-weighted imaging, and a
high signal intensity in T2-weighted imaging
[42]. They may enhance with gadolinium.
Sensitivity ranges from 50 to 88% [8, 13, 35–38,
41, 43, 46–50]. Like CT, MRI is particularly useful
for identifying ectopic parathyroid adenomas.
Sensitivity approaches 90% for adenomas in the
mediastinum. False-positive results are due to
enlarged lymph nodes and thyroid abnormalities.
MRI has significant drawbacks; size of detection is
limited to adenomas >5 mm, and localization
of the superior glands is problematic since they
lie posterior to the thyroid.
MRI is usually reserved as a second line
test for localization in reoperative parathyroid
surgery when US and sestamibi scan have failed
to identify an abnormal parathyroid gland
which is probably located in the mediastinum.
Positron Emission Tomography
Positron emission tomography (PET) imaging
has been reported in limited studies. Three
radiopharmaceutics have been evaluated:
18
F-fluorodeoxyglucose (18F-FDG),11C-methio-
nine, and
18
(
F-FDOPA) [51, 52]. Methionine PET scanning
18
F-fluorodihydroxyphenylalanine
was found to have a high sensitivity (about
85–90%); however, 11C-methionine has the
practical disadvantage that the half-life of
very short (20 min) and requires an on-site
cyclotron.
18
F-FDG is less sensitive.18F-FDOPA
11
Cis
is unable to detect parathyroid adenomas and
should not be used [53]. CT-PET co-registration
is useful for localizing ectopic adenomas.
Currently, PET cannot be recommended for
routine use and should be reserved for patients
with persistent or recurrent HPT, when other
tests have been unhelpful. In addition, PET is
not available in all centers and the cost is high
compared with other investigations.
Invasive Tests
Selective Venous Sampling
SVS for PTH measurement requires an experienced and skilled interventional radiologist.
It is a very sensitive test which depends on
gland function rather than size. Establishing an
angiographic roadmap is recommended before
performing SVS. Venous catheterization is performed through a femoral vein with sampling
from large veins such as the jugular vein, innominate vein, superior cava. Smaller veins, such
as superior, middle, and inferior thyroid veins
are sampled when present, as arethe thymic and
vertebral veins. The samples must be taken as
selectively as possible from the smallest venous
branches to provide a precise gradient map as a
guide for the surgeon [54]. A gradient of at least
twofold in the PTH level is required for a result
to be significant [49, 55–58].
In the published reports, sensitivity and
specificity of the SVS range from 63 to 94.7%
and 86 to 100%, respectively [59].
245
PARATHYROID LOCALIZATION AND IMAGING
SVS cannot be routinely proposed because of
the associated risks of morbidity; venous
thrombosis, hematoma, prolonged radiation
exposure, and contrast load. In addition, it is
an expensive technique. It should be reserved
for reoperative parathyroid surgery when other
investigations have failed.
Selective Angiography
Proper parathyroid angiography includes
examination of the thyrocervical trunks for
glands in lower cervical sites, the carotid
arteries and superior thyroid arteries for upper
cervical sites, and internal mammary arteries
for thymic and mediastinal sites. Parathyroid
adenomas appear highly vascularized with an
ovoid or round blush. Adenoma size limit is
4 mm. Sensitivity approaches 60% [8, 60, 61].
False positives are due to thyroid nodules and
enlarged lymph nodes. In selected cases, it is
possible to perform angiographic embolization
of the adenoma [62]. This technique is only
indicated for poor-risk surgical patients with
persistent HPT related to a mediastinal parathyroid adenoma.
As in SVS, parathyroid angiography is a
difficult and expensive technique with potentially serious complications. For these reasons
it should be reserved for reoperative localization when other tests have failed.
Fine Needle Aspiration
FNA performed under sonographic or CT
guidance may help distinguish a parathyroid
tumor from other structures. It is a minimally
invasive test used in reoperative cases to confirm the diagnosis of parathyroid tissue. PTH
determination is more helpful than cytological
examination because the sample may be insufficient and because differentiating between
parathyroid and thyroid tissue can be difficult.
FNA with PTH determination is highly sensitive
and specific [10, 63]. The use of FNA is limited
in small adenomas. FNA can be combined with
alcohol ablation but persistent or recurrent
HPT is likely and the procedure has to be
repeated [64]. In addition inferior laryngeal
nerve injury has been reported. This nonoperative procedure requires an expert radiologist
and should be reserved for patients refusing
surgery.
Intraoperative Tests
The Parathyroid Surgeon
Although today many modalities of parathyroid localization are available, one should keep
in mind that the success of a parathyroid
operation is above all based on the experience
of the surgeon, a thorough knowledge of
the anatomy, and on an understanding of the
embryological evolution of the glands. The
failure rate of an initial cervical exploration
performed by an experienced parathyroid
surgeon does not exceed 5%. Ideally, the failure rate should not exceed the incidence
of ectopic glands deeply located in the mediastinum and inaccessible from a cervical
approach. Without preoperative localization,
the experienced parathyroid surgeon is still
one of the most sensitive, specific, and cost
effective ‘‘tools’’ to identify an abnormal parathyroid gland.
Methylene Blue Staining
An intravenous infusion of saline mixed with
methyleneblueisgivenafteranesthesia
induction: abnormal parathyroid glands
stain a dark to light blue whereas normal
glands remain unstained. This method speeds
identification of the glands in initial operation, and has been reported to be safe, effective, and inexpensive but is today used by few
surgeons [65].
Intraoperative US
Intraoperative US using a 10-mHz transducer
may be useful in reoperative cases. The procedure is performed with either a dedicated sterile
intraoperative transducer or one draped in a
sterile sheath. It requires a learning curve. This
method has been particularly recommended for
the identification of adenomas hidden in dense
scar tissue and for intrathyroidal parathyroid
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ENDOCRINE SURGERY
adenomas. Operating time can be reduced
significantly [66].
Radio-Guided Parathyroid Surgery
This test is characterized by the use of an
intraoperative probe to direct the dissection
according to the level of radioactivity [67].
The operation must be carried out within
3.5 h of the radiopharmaceutical injection.
There is a ‘‘window’’ of optimal timing
between injection of the pharmaceutical
agent (
in the operating room. The optimal situation
occurs when the thyroid has washed out its
nuclear tag and the parathyroid remains
radioactive. Typically, a window between 1.5
and2.5hisidealforthevastmajorityof
patients. Resected adenomas emit radioactivity of greater than 20% of the post excision
background activity. This confirms the diagnosis of hyperfunctional parathyroid tissue
and reduces the number of diagnostic frozen
sections. Fat, lymph nodes, and thyroid
nodules do not show this level of radioactivity.
When exploring the superior mediastinum it
must be remembered that false-positive readings can be due to radioactivity emitted by the
heart.
used in both initial surgery and reoperative
cases. It has the potential to reduce operative
time [68]. It does not require the use QPTH
measurements [67]. Excellent results have
been reported [69].However, controversy
exists, and some authors consider that radioguided parathyroidectomy does not add a significant advantage, and is heavy and time
sensitive to apply [70].
99m
Tc sestamibi) and using the probe
Radio-guided parathyroid surgery can be
Intraoperative SVS for QPTH
Measurement
The intraoperative QPTH assay enables the
surgeon to perform SVS by direct punction
into both internal jugular veins and innominate
vein. This technique can help the surgeon,
during the procedure, to localize or lateralize
a hypersecreting gland in the neck or in the
superior mediastinum.
Indications for Localization
Tests
One should emphasize that parathyroid imaging is
not a technique that should be used to make or
to confirm the diagnosis of HPT; this is achieved
by metabolic testing. This is a fundamental point
particularly when a parathyroid tumor is incidentally discovered during US examination indicated
for thyroid disease.
Are parathyroid localization studies useful?
The answer is yes, but they must be selected
according to availability, experience, success
rate, cost, benefit, and risk for the patient. The
least invasive and the least costly studies should
be used first. Today one can consider that:
1 There is a debate regarding the routine use of
localization studies for initial standard cervi-
cotomy in patients with primary HPT.
2 The role of imaging studies prior to initial
surgery in patients with secondary/tertiary
HPT also remains controversial.
3 Preoperative localization is mandatory for
focused parathyroid approaches.
4 Preoperative imaging is undeniably valuable
for patients who have persistent or recurrent
HPT.
Initial Bilateral Cervical Exploration
In the past, routine preoperative imaging for
initial bilateral parathyroid exploration was
considered unnecessary and not cost effective
(Dopmann) [1]. Indeed, when performed by an
experienced endocrine surgeon, the success rate
of this procedure was reported to be 95–98%
[71]. The failure rate, in most cases related to
ectopic glands, not in the neck but located deeply in the mediastinum and virtually inaccessible from the cervical route, was considered too
low to justify systematic preoperative imaging.
Nevertheless, not all parathyroid operations are
performed by expert parathyroid surgeons, and
there has been improvement in noninvasive
localizing techniques. This explains that an
increasing number of authors currently advocate the use of preoperative localization of
abnormal parathyroid glands before all
parathyroidectomies.
Moreover, because most surgeons accept
that bilateral cervical exploration is not the
247
PARATHYROID LOCALIZATION AND IMAGING
only indicated procedure in a patient with a
solitary parathyroid adenoma, parathyroid
surgeons are today highly dependent upon the
result of preoperative imaging to make a judicious
choice between a bilateral cervical exploration
and a focused approach. Once contraindications
have been eliminated, all patients with sporadic
primary HPT who are considered potential candidates for a Focused parathyroidectomy must
undergo localization studies. These procedures
will only be indicated for patients in whom a
single adenoma has beenclearly localized. In
mostcentersthisisanargumentfortheroutine
use of US and sestamibi scan in all patients with
untreated primary HPT.
Numerous benefits of the successful localization of abnormal parathyroid glands have been
reported. Proper localization directs and limits
surgical exploration and therefore may reduce
surgical failure rate, complication rates, and
operative time [72–74].
Only an inexpensive, highly sensitive and
highly specific and noninvasive test should be
considered for initial standard cervicotomy.
This test does not exist but many authors routinely use US and/or sestamibi scan. According
to the availability and experience in different
centers these localization studies can help the
surgeon by localizing the abnormal gland.
Other tests are not indicated even when both
US and sestamibi scan are negative. It remains
questionable whether the routine use of US
or sestamibi scan is justified and financially
sustainable in all cases of primary HPT [75].
Secondary/Tertiary HPT
Whether preoperative localization studies are
helpful to achieve complete parathyroid identification in renal HPT remains controversial. Many
authors consider that localization prior to initial
surgery does not have a significant role in planning
the surgical intervention and is unnecessary as
these patients systematically undergo a bilateral
cervical exploration, to identify all four glands
and to search for a supernumerary gland in the
neck or superior mediastinum.
The aim of imaging when used in secondary/
tertiary HPT is to limit the surgical exploration,
reduce the operative time, and above all to
detect supernumerary and ectopic glands that
are present in up to 25% of patients. Prior to
initial surgery, only noninvasive imaging tests
should be considered, i.e., US/sestamibi scans as
first line, and CT or MRI when there is suspicion
of an ectopic mediastinal location. Patients with
secondary HPT tend to have large glands and
the sensitivity and specificity of these imaging
modalities are higher than for primary hyperplasia. A sensitivity of 45–70% for US and of
30–65% for sestamibi scanning has been
reported [76–78]. However, it is very rare that
all four glands are imaged in the same patient.
Minimally Invasive
Parathyroidectomy
The concept of new minimally invasive techniques is based on the fact that 85% of patients
will have single-gland disease. The common
thread of new minimally invasive techniques is
that the approach is targeted on one specific
parathyroid gland. In most cases the exploration of other glands is not performed. Therefore, the success of limited techniques largely
depends on accurate preoperative localization.
Because surgery is targeted on one specific
gland, patients suspected of having multigland
disease are not suitable for these limited procedures. Today the surgeon is therefore highly
dependent upon the quality of preoperative
localization to make a judicious choice for
either a focused or a conventional approach.
Most institutions use US or sestamibi scan,
either alone or most commonly in combination.
These imaging studies complement each other.
Sestamibi scan allows identification of hyperfunctioning glands but provides few anatomic details.
In contrast, US provides little information about
function but is much more informative about
anatomic detail. If the US and the nuclear scan
do not correlate with a solitary lesion at the same
site, a traditional 4-gland open procedure is
preferable. However, if the lesion is solitary and
confirmed by both studies, a focused procedure
can be proposed. It has been demonstrated that
the risk of MGD is nearly zero when both studies
are positive and concordant. In this case the use
of QPTH is questionable. The risk of MGD has
been found to be 3.6% when only one imaging
method is positive [32]. When available, 4D-CT,
providing both anatomic and functional information can be used instead of both US and sestamibi
scan [45].
248
ENDOCRINE SURGERY
Preoperative imaging may also have a role
for the choice between different focused
approaches described [79]. Depending on a
posterior or anterior location of the adenoma
in the neck, the surgeon can choose a central or
a lateral approach. The lateral approach, which
allows direct access to the lateral and posterior
aspects of the thyroid lobe, is particularly suitable for patients with adenoma located posteriorly in the neck. In contrast, the central access
is more convenient for patients with inferior
parathyroid adenomas located superficially in
the neck or in the superior mediastinum.
Finally, preoperative imaging may also have a
role for thechoice between a mini-open procedure
or a video-assisted or endoscopic procedure [80].
The need for an endoscope during minimaly invasive parathyroidectomy (MIP) may be determined
by the location of the parathyroid adenoma. In
our opinion, the use of the endoscope must be
recommended when the parathyroid adenoma
becomes intimate with the recurrent laryngeal
nerve, that is, when the adenoma is located in
the retro-thyroidal area. The endoscope offers
not only a magnified view of anatomical details
but also a perfect lighting of the area of dissection.
The quality of the surgical image provided by the
endoscope is undoubtedly superior to the one
obtained with frontal lamps and magnifying
loupes. We consider that mini-open approaches
using a skin incision of no more than 2 cm should
be used only when the nerve is not at risk during
the dissection, which is when the adenoma is
superficially located in the neck. Therefore the
need to know preoperatively when the nerve is at
risk reinforces the role of imaging studies for
localizing deep-seated adenomas.
Persistent or Recurrent HPT
The diagnosis of persistent or recurrent PHPT
must be reconfirmed biochemically and must be
unequivocal. Once again, the surgeon should
keep in mind that the diagnosis of PHPT is not
established by parathyroid imaging, and that
false-positive results of imaging techniques do
exist. Once the diagnosis has been reconfirmed,
the potential benefit of reoperation must be
weighed against the operative risk in the individual patient. For example, mild asymptomatic
hypercalcemia, which was considered an indication for primary surgery, may not necessarily
justify the risks of reoperation.
It has been demonstrated that when the first
operation is performed by an inexperienced
surgeon, reoperation by a more expert surgeon
is successful in 95% of cases without any preoperative tumoral localization [81–83]. Nevertheless,
today preoperative imaging is undeniably
valuable for any patient who has persistent or
recurrent HPT and particularly for patients who
have been operated on by expert surgeons.
Apart from improving the prospects of success,
preoperative localization of the tumor reduces
the operating time and the operative morbidity.
Today, most parathyroid surgeons consider that
surgery for persistent or recurrent HPT should
be performed only after positive localization
studies.
Many modalities of noninvasive and invasive
imaging can be applied preoperatively to localize the parathyroid glands. These modalities
should be selected according to availability,
cost, and experience. The topographic diagnosis
should ideally be established by concordant
results of two different investigations, one providing good anatomic information and the
other providing functional information.
Therefore, most authors consider that US
and sestamibi scan should be performed routinely as the first-line work up for persistent or
recurrent HPT. When these two tests suggest a
unique enlarged and hyperfunctional gland in
the neck further additional localization is not
required.4D-CT,whenavailable,isanalternative to US/sestamibi [45].When a sestamibi
scan suggests an ectopic mediastinal location,
CT or MRI are mandatory to confirm the localization and to give additional anatomic information. CT scan and MRI are also indicated for
patients in whom both US and sestamibi scan
have failed to localize a lesion. The appropriate
approach to the mediastinum is dependent upon
the precise localization. Most mediastinal
adenomas located in the posterior or anterior
mediastinum above the aortic arch can be
excised through the neck [13, 35, 36, 40, 44,
84, 85]. Only adenomas located deep in the
anterior or middle mediastinum require a thoracic approach. Precise localization can allow
approaches less invasive than a sternal split or
thoracotomy. Mini-anterior mediastinotomy or
left thoracoscopy may be preferable to a partial
or a total sternotomy [86, 87].
When sestamibi or US scans are equivocal,
image-guided FNA may help distinguish a
249
PARATHYROID LOCALIZATION AND IMAGING
parathyroid tumor from other structures in the
neck. For a suspected mediastinal localization,
when sestamibi, CT, or MRI are equivocal, PETFDG may be useful.
Invasiveprocedures including SVS forPTH or
selective angiography, should be performed only
if noninvasive procedures are inconclusive.
After total parathyroidectomy and autotransplantation in patients with renal HPT,
recurrences can occur not only on the grafts
but also secondary to a supernumerary gland
in the neck or the mediastinum. When there
is no evidence that the recurrence is graftdependant, the Casanova test can be used to
evaluate whether the origin of the recurrence is
a residual gland or grafted tissue [88].
Finally, whether reoperative surgery is
indicated when localization studies are negative
remains questionable. The surgeon must keep
in mind that localization failures may be due to
an incorrect diagnosis. With the advent of a
reliable radioimmunoassay for intact PTH,
other causes of hypercalcemia can be easily
eliminated. Particular thought should be given
to the syndrome of benign familial hypocalciuric hypercalcemia (BFHH). It has also been
reported that 1 month after surgery for primary
HPT, elevated serum PTH levels are observed
in up to 30% of patients despite normalization
of calcium levels. In some cases elevated PTH
levels are anadaptative reactionto renal dysfunction or vitamin D deficiency. It has also been
demonstrated that these patients can show
decreased peripheral sensitivity to PTH [89].
If thediagnosis of HPT remains unequivocal
the persistent or recurrent disease is more
likely due to parathyroid hyperplasia than solitary adenoma. In our experience, negative preoperative localization studies are highly predictive of MGD [32]. The sporadic or familial
nature of the HPT should be determined. Study
of the operative and histology reports from
previous operations may be useful to determine if there is a possibility of an MGD or, of
an undiscovered solitary adenoma. If biopsy
has not been performed, the reported identification of a parathyroid gland is questionable.
The number of glands identified, their gross
appearance, and possible excision should be
carefully noted. Their embryonic origin, e.g.,
third or fourth branchial pouch, should be
determined.Anunderstandingoftheembryonic development and the embryonic migration
of the parathyroid glands is of paramount
importance in these circumstances. In our opinion, in the absence of localization, only cervical reoperation may be indicated. Mediastinal
explorations using a thoracic access are too
invasive and too hazardous to be recommended. When there is a strong suspicion of
MGD the suggested operation is a revision of
thetransversecervicotomy.Theentireparathyroid system must be explored. This also
involves a search for supernumerary glands
and a bilateral thymectomy if not previously
excised. When a nonlocalized parathyroid adenoma is suspected, the procedure may be more
selective and guided by the results of previous
operations. When available, intraoperative
ultrasound and gamma-probe may be helpful
here. QPTH monitoring and cryopreservation
are also recommended in these patients. Other
possible causes of persistent or recurrent disease, without confirmatory localization studies, are parathyroid carcinoma and parathyromatosis. Patients, previously operated on for
parathyroid carcinoma, may have multiple
undetectable metastatic lesions. In the case of
parathyromatosis, multiple small nodules of
hyperfunctioning parathyroid tissue, locally
scatteredintheneck,maybealsonotvisualized by localization studies. In both scenarios
medical therapy should be considered.
Conclusion
Refinements in parathyroid localization studies
have led to a reassessment of their role in the
management of patient with HPT. Twenty years
ago the role of parathyroid localization was as a
preoperative localization procedure. Because
bilateral neck exploration was the only surgical
option and because this procedure was successful in 95–98% of cases when performed by
experienced endocrine surgeons, preoperative
localization in patients with untreated HPT
was rarely indicated and was reserved for
patients with persistent or recurrent disease.
In recent years, there has been a progressive
shift in the management of patients with HPT
that has been driven by technological advances.
Improvement in noninvasive localizing techniques is certainly the main factor that today
enables the surgeon to perform focused