The parathyroid glands are located posterior to the thyroid gland in the neck. Parathyroid adenomas, the most common cause of primary hyperparathyroidism, enhance vividly on arterial phase CT then wash out rapidly on delayed phase with low attenuation on non-contrast images. Localizing the adenoma precisely with 4D CT guides focused surgical treatment through a small incision. The characteristic enhancement pattern and morphology help identify ectopic adenomas located during fetal development in the mediastinum.

2. ANATOMY
Parathyroid glands are located within the
visceral space of the neck, posterior to the
thyroid gland, in the vicinity of the
tracheoesophageal groove.
They may be located either inside or
outside the thyroid capsule.

3. SUPERIOR PARATHYROID GLAND
Arises from the 4th branchial pouch, during fetal development,
migrates with the thyroid gland.
Eutopic superior parathyroid glands are located on the posterior
aspect of the superior or middle third of the thyroid lobe in more
than 90% of the general population.
Ectopic superior parathyroid gland may be
above the upper pole of the thyroid lobe (<1%)
posterior to the pharynx or esophagus, in either the neck or the
superior mediastinum (1%–4%)
intrathyroidal (<3%)

4. INFERIOR PARATHYROID GLAND
Arises from the 3rd branchial pouch, migrates with thymus.
Eutopic inferior parathyroid glands are located at the level
of the inferior pole of the thyroid lobe, in its posterior,
lateral, or anterior aspects (61%).
Ectopic inferior parathyroid glands may be located in the
neck, inferior to the lower pole of the thyroid lobe, in the
anterior mediastinum (4%–5%); intrathyroidal (<1%–2%).
In the anterior mediastinum, inferior parathyroid glands
may be situated within the thymus, at the posterior aspect
of the thymic capsule, or in contact with the great vessels of
the mediastinum

5. PRIMARY HYPERPARATHYROIDISM
four times more common in women than in men and is
most prevalent in the 5th to 7th decades of life
signs and symptoms of hyperparathyroidism largely
represent hypercalcemia, which may affect multiple systems
Symptomatic patients at presentation can have recurrent
kidney stones, osteopenia, hypertension, peptic ulcer
disease, mental status changes, and fatigue

6. Most cases of primary hyperparathyroidism are caused
by a solitary parathyroid adenoma (88%).
Other less common causes are multiglandular disease
from double adenoma (4%) and multiple gland
hyperplasia (6%), and rarely, carcinoma ( 1%)
increased incidence of parathyroid hyperplasia in MEN
type I and type IIA.

7. To select patients for minimally invasive parathyroidectomy
surgery, the surgeon needs precise localization of the
parathyroid adenoma and to exclude multiglandular
disease

8. IMAGING

9. ULTRASOUND:
Parathyroid adenomas are
homogeneously hypoechoic to the
overlying thyroid gland.
Larger adenomas can be multilobulated
Color Doppler imaging commonly show a
characteristic extrathyroidal feeding
vessel (typically a branch off the inferior
thyroidal artery), which enters the
parathyroid gland at one of the poles

10. 4D CT TECHNIQUE
The role of four-dimensional (4D) CT is to enable accurate
localization of the parathyroid adenoma and to depict multiglandular
disease
The 4D CT protocol is composed of multiple phases (typically two to
four phases) and reformatted images in three planes.
The first three “dimensions” are multiplanar CT: axial acquisition
with coronal and sagittal reformations.
The fourth “dimension” of 4D CT is change in enhancement overtime
from non– contrast-enhanced, arterial, and delayed (venous) phase
imaging.

11. The characteristic contrast enhancement pattern of a
parathyroid adenoma is peak enhancement on the arterial
phase, washout of contrast material from the arterial to
delayed phase, and low attenuation on the non–contrast
enhanced images .
Four-dimensional CT has high accuracy in localizing an
adenoma to a quadrant (87%) when used as a firstline
investigation.

13. DIFFERENTIAL DIAGNOSIS
The two main mimics of parathyroid adenomas- lymph nodes and
thyroid tissue.
Lymph nodes show progressively increasing enhancement after
injection of contrast material, with peak enhancement at 90
seconds corresponding to the delayed phase.
Thyroid tissue can enhance intensely in the arterial phase but will
also have increasing contrast enhancement between the arterial
and the delayed phases when the attenuation is measured .
In addition, thyroid tissue will have intrinsic high attenuation on
the non–contrast-enhanced images because the thyroid gland is
iodine-containing

14. The feeding artery is usually a branch of the inferior thyroid artery,
and the artery can be tortuous and enlarged in the setting of
adenoma because of its increased blood flow An enlarged adjacent
vessel may also be an enlarged draining vein
The polar vessel sign can be present in up to two-thirds of
parathyroid adenomas on 4D CT images

16. PARATHYROID SCINTIGRAPHY
Three general techniques of radionuclide scintigraphy are
commonly used for the detection and visualization of
hyperfunctioning parathyroid glands:
1. single-phase dual-isotope subtraction imaging,
2. dual-phase single-isotope imaging, and
3. a combination of the two

17. Single-isotope dual-phase imaging technique was proposed
on the basis of the difference between the rate of 99mTc
sestamibi washout from the thyroid gland and the rate of
washout from hyperfunctioning parathyroid glands, which
is typically slower.
This technique requires a single injection of 99mTc
sestamibi, followed by imaging at approximately 10–15
minutes and 1.5–3 hours after the injection.

18. 99mTc sestamibi consists of lipophilic cationic molecules.
The detectability of parathyroid adenomas and hyperplastic
parathyroid glands is related to the presence of mitochrondria-
rich oxyphil cells.
99mTc sestamibi normally is distributed to the parotid and
submandibular salivary glands, thyroid gland, heart, and liver;
uptake is not seen in normal parathyroid glands.

20. Images show delayed washout in a large right inferior
a) parathyroid adenoma that extends from the inferior pole of the right thyroid lobe to
the superior mediastinum.
b) early washout in a large thyroid adenoma, which extends from the lower pole of the
left thyroid lobe to the superior mediastinum

21. Dual-isotope subtraction imaging techniques is by using
99mTc sestamibi and 123I or 99mTc pertechnetate.
99mTc pertechnetate, which is taken up only by the
thyroid.
subtraction of thyroid images obtained with iodine-123
(123I) or 99mTc pertechnetate from those obtained with
99mTc sestamibi.
Evidence of residual radioactivity on the subtraction
image represents a hyperfunctioning parathyroid gland

22. MRI
MRI is used in patients with persistent or recurrent
hyperparathyroidism, in whom it has been shown to be
effective in locating remaining abnormal parathyroid tissue.
The T1 and T2 characteristics of abnormal parathyroid
tissue are variable.
The most common tissue characteristics are intermediate-
to low-intensity T1 signal and high-intensity T2 signal.
false-negative studies are most commonly associated with
adenomas that are isointense on T1 and T2 sequences; the
addition of contrast-enhanced images can increase
sensitivity for these cases

24. SURGICAL TREATMENT
A single parathyroid adenoma is now most commonly
resected through a smaller unilateral incision on one side of
the neck in one quadrant.
The other glands are left unexplored if the venous
intraoperative parathyroid hormone level drops following
resection.
A decrease of more than 50% from the baseline PTH value
at 5–10 minutes after resection is suggestive of a single site
of primary hyperparathyroidism.

26. The parameters for all three phases are the following:
0.625-mm section thickness;
tube rotation time, 0.4 second; pitch factor, 0.516:1;
field of view, 20 cm; 120 kVp; and automatic tube current
modulation.
Tube current modulation (mA Modulation; GE Healthcare) is used
with a noise index of 8, minimum 100 mA, and maximum 400 mA
for the nonenhanced phase and delayed phase and 600 mA for the
arterial phase.

27. SYSTEMATIC APPROACH TO 4D CT
Step 1: Review for Lesions in Eutopic Locations in Arterial
Phase.
The superior parathyroid gland has a more consistent location
posterior to the mid-to-upper third of the thyroid gland . The
inferior parathyroid gland lies inferior, lateral, or posterior to
the lower third of the thyroid
The arterial phase should be the focus of the initial review
because this is the phase in which the attenuation of the
parathyroid adenoma will be highest, with reported mean
attenuation ranging from 138 to 180 HU

28. Step 2: Review for Lesion in Ectopic Locations in Arterial Phase
Ectopic parathyroid adenomas and ectopic parathyroid hyperplasia
account for 20%–25% of cases
The inferior glands -third branchial pouch and the superior glands -
fourth branchial pouch.
These pouches are approximately at the level of the bifurcation of
the carotid artery.

29. During fetal development, the inferior gland migrates with the
thymus.
So an ectopic inferior gland may be in any location from the carotid
bifurcation to the anterior mediastinum, including within the
thymus or the thyroid gland.

30. There is less variation in the location of the superior parathyroid,
which migrates with the thyroid gland. Rare sites for an ectopic
superior parathyroid gland are in the retropharyngeal space or
intrathyroid
More commonly, a superior parathyroid adenoma -pseudoectopia
due to the enlarged gland falling caudally and posteriorly in the
tracheoesophageal groove .
Thus a posterior mediastinal parathyroid adenoma is more
characteristic of a superior parathyroid adenoma that has fallen
caudally.
In contrast, an anterior mediastinal parathyroid adenoma will be
from the inferior parathyroid gland and along the thyrothymic
ligament

31. Step 3: Compare Other Phases for Characteristic Enhancement
Characteristic enhancement for a parathyroid adenoma is vivid
contrast enhancement in the arterial phase, rapid washout of
contrast material in the delayed phase, and lower attenuation
compared with thyroid gland in the nonenhanced phase
The peak enhancement has been described as between 25 and 60
seconds after injection

33. Step 4: Evaluate for Characteristic Morphology
A parathyroid adenoma is oval or rounded with margins that are
smooth or slightly lobulated
Other shapes of parathyroid adenomas are teardrop, discoid,
tubular, and pyramidal
Lobulated margins and cystic component help differentiate a
candidate lesion from a normal lymph node. Normal lymph nodes
have smooth margins and are solid or have fatty hila

34. Step 5: Compare CT Findings with Other Modalities and History
If there is a candidate lesion at 4D CT examination, the other
studies should be reviewed to determine if the studies are
concordant