Joint Program in Nuclear Medicine
Tc-99m Sestamibi Scintigraphy in Primary Hyperparathyroidism
Chandra Dass, MD
J. Anthony Parker, MD PhD
October 1, 1996
Presentation
A 35 year old female presented with renal stones, and was found to have
hypercalcemia and elevated parathormone. A diagnosis of primary hyperthyroidism
was made. Ultrasound was negative and bilateral neck exploration documented
normal appearing glands and no parathyroid adenoma.
Imaging Findings
Sestamibi scintiscan was positive for ectopic parathyroid adenoma in the
superior mediastinum on the left side. Planar
images at 20 minutes (top) and 2 hours (bottom) show a persistent focus
of increased uptake in the mediastinum (shown
by black arrow; thyroid is seen on 20 minute images, black arrow heads,
but not on the 2 hour image; marker images on the right shows the sternal
notch and 10 cm above the sternal notch, white arrows; left arm vein uptake
is the route of injection, white arrow heads). SPECT
images (transverse, coronal, and sagital) show the location of the
lesion (shown by arrows).
A subsequent CT of the chest revealed a nodule
(shown by arrow) in the aortico-pulmonary window.
CT reconstruction further defines the location
of the lesion (shown by arrow). Since the
angio was negative, catheter mediated ablation procedure was abandoned.
Clinical Course:
A left thoracotomy was performed and an adenoma was removed from the left
tracho-bronchial angle. Post operative period was marked by frequent episodes
of symptomatic hypocalcemia as expected, and the patient was managed accordingly.
Diagnosis
Mediastinal Parathyroid Adenoma
Discussion
Primary hyperparathyroidism is a relatively common disease, occurring in
about one of every 500 women over 40 years of age and in about one of every
2000 men. Most cases (80-85%) of primary hyperparathyroidism are the result
of single adenomas. Most of the remaining are hyperplasia with a small
number of carcinomas. Although 80-85% of parathyroid adenomas are found
adjacent to the thyroid gland in their normal location, the remaining are
ectopic (thymus, superior mediastinum, upper neck). Inferior parathyroids
are more often ectopic than the superior parathyroids for embryological
reasons.
Surgical exploration and the removal of the adenomatous gland is the
treatment of choice. Since the success rate for parathyroid surgery has
been reported to exceed 90%, the need for preoperative localization is
a matter of debate. Localization techniques are more useful in cases of
failed primary neck exploration and in cases of postoperative persistent
hypercalcemia. Anticipated technical difficulties and patients with high
risk factors may be the indications for localization studies prior to a
primary neck exploration (1).
Mechanism of uptake:
Parathyroid glands are richly vascularized from branches of the superior
and inferior thyroid artery. The chief cells compose the majority of the
gland and secrete parathormone (PTH). The oxyphil cells, of uncertain function,
are rich in oxidative enzymes and contain abundant mitochondria. Tc-99m
Sestamibi (MIBI) moves by passive diffusion across plasma and mitochondrial
membranes. The net cellular uptake and retention of sestamibi depends on
the electrical potential generated across the membrane bilayers of both
the cell and the mitochondria. Normal or abnormal tissue with a large number
of mitochondria have been correlated with increased avidity for sestamibi
than tissues with less mitochondria. The exact mechanism of sestamibi uptake
in parathyroid adenomas are not precisely known at the present time. It
is likely that many factors (cationic charge, lipophilicity, degree of
perfusion, transmembrane gradient, p-glycoprotein) are involved. Available
data suggest that the presence of mitochondria rich oxyphil cells can be
a significant factor influencing the detectability of the abnormal parathyroid
glands. On this basis, it is possible that sestamibi would be taken up
more avidly by adenomatous tissue than the surrounding thyroid parenchyma.
Imaging protocol:
Two distinct types of data acquisition protocols are described while using
sestamibi for parathyroid adenomas. The first uses sestamibi as a substitute
to Tl-201 in a dual radionuclide approach with subtraction imaging (with
either I-123 or Tc-99m pertechnetate) and the second approach uses sestamibi
alone (single radiotracer) with early and delayed imaging (double phase
study). The later imaging protocol is based on the differential washout
of the sestamibi in the thyroid and parathyroid lesions.
Dual radionuclide subtraction imaging:
Coakley et al. (2,3) were the first to suggest the clinical use of sestamibi
as a substitute to Tl-201 for parathyroid imaging in the dual radionuclide
protocol. Out of the 57 studied patients (40 adenomas, 15 hyperplasia,
2 carcinomas) the sensitivity of Tl-201 and sestamibi were 92.5% and 97.5%
respectively for adenomas. Both agents were less sensitive for detecting
glandular hyperplasia, with 48.3% for Tl-201 and 53.3% for sestamibi. No
false positive was reported. The data obtained from the dynamic curves
for Tl-201 and sestamibi uptake showed that the uptake appears to reach
a maximum at 4-6 minutes in both the thyroid tissue and the parathyroid
adenoma. But the differential uptake between the thyroid tissue and the
parathyroid adenoma was higher for sestamibi than Tl-201. More over the
sestamibi activity in the parathyroid tissue remained relatively constant
following the peak activity, where as Tl-201 activity steadily declined.
Activity over the thyroid fell with both tracers over time. The authors
postulated that the marginal improvement of sestamibi compared to Tl-201
might be explained by different factors: the better imaging characteristics
of Tc-99m, higher differential uptake between thyroid and parathyroid adenoma
with sestamibi (better target to background ratio), greater retention of
sestamibi by parathyroid adenoma and possibly the higher injected activity
of sestamibi compared with Tl-201.
Dual phase sestamibi imaging:
The drawbacks inherent in the dual radionuclide imaging (related to the
type of tracer, injection sequence, computer alignment and subtraction)
are potentially overcome by the single radiotracer-double phase protocol
using sestamibi. The net retention of sestamibi in thyroid decreases significantly
more rapidly than in parathyroid adenoma over time (1-3 hours post injection).
The thyroid/parathyroid differential washout of sestamibi is the rationale
for single radiotracer protocol (4). Two sets of images were obtained,
the initial set at 20 min. post injection is called the “thyroid phase”
of the study and the second set obtained at 2 hours is called “parathyroid
phase” of the study. Positive study for the presence of parathyroid adenoma
is defined as a focal area of increased uptake in the thyroid bed and surrounding
areas or suspected ectopic sites, that showed either a relatively progressive
intensity over time or a fixed uptake that persisted on the delayed imaging,
contrary to the uptake in the surrounding normal thyroid tissue which progressively
decreases over time.
The sensitivity (90%) and the specificity (90%) were reported to be
comparable to that of dual radionuclide protocol (1). The parathyroid phase
images (delayed) alone are sufficient for diagnosis. However, the thyroid
phase images are helpful and used as an anatomical reference to locate
the abnormal focus of persistent uptake since the normal thyroid tissue
is usually only faintly seen on the delayed images (4). The most common
cause of false positive localization is the underlying thyroid disease
(especially follicular adenoma). Several techniques are suggested (routine
palpation for thyroid nodules, further delayed images at 5-6 hours, dual
radionuclide imaging, SPECT imaging) to overcome these pitfalls.
Other Methods:
Other noninvasive modalities used for localization are high resolution
US (10 MHz), CT and MRI. Ultrasound is at its best in detecting adenomas
at the lower pole of the thyroid. However, these adenomas are the easiest
for the surgeon to find. Ultrasound performs poorly in detecting ectopic
adenomas. CT and MRI may be unreliable in patients with history of previous
neck surgery. Selective venous parathormone sampling and arteriography
are less often used because they are more invasive, expensive and lack
sensitivity (5).
Conclusion:
The primary virtues of scintigraphy are that its sensitivity and specificity
are not affected by the previous surgery and its ability to localize ectopic
adenomas. The primary problem is that thyroid gland abnormalities decrease
the sensitivity and the specificity. However, the exact role of scintigraphy
in parathyroid disease remains yet to be defined.
References
1.Taillefer R., Tc-99m Sestamibi parathyroid scintigraphy. In Nuclear Medicine
Annual 1995, Raven Press, Ltd., New York 1995; 51-79.
2. Coakley AJ, Kettle AG, Wells CP, et al. 99mTc sestamibi a new agent
for parathyroid imaging. Nuc Med Commun 1989;10:791-794.
3. O’Doherty MJ, Kettle AG, Wells CP, et al. Parathyroid imaging with
Tc-99m sestamibi: preoperative localization and tissue uptake studies.
J Nuc Med 1992; 33:313-318.
4. Taillefer R, Boucher Y, Potvin C, et al. Detection and localization
of parathyroid adenomas in patients with hyperparathyroidism using a single
radionuclide imaging procedure with Tc-99m sestamibi (double phase study).
J Nucl Med 1992; 33: 1801-1807.
5. Beierwaltes W; Endocrine imaging: Parathyroid, Adrenal cortex and
medulla and other endocrine tumors. Part II. J Nucl Med 1992; 32:1627-1639.
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J. Anthony Parker, MD PhD, Tony_Parker@bidmc.harvard.edu
