Update to the previous presentation. Several cases have been added

1. NUCLEAR MEDICINE
APPLICATION IN
PARATHYROID DIORDERS:
AN EVIDENCE BASED
APPROCH
Ramin Sadeghi, MD

2. HYPERCALCEMIA
Hypercalcemia is a relatively common clinical problem.
Among all causes of hypercalcemia, primary hyperparathyroidism and
malignancy are the most common, accounting for greater than 90
percent of cases

4. INTERPRETATION OF SERUM
CALCIUM
In almost all patients, hypercalcemia is due to an elevation in the
physiologically important ionized (or free) calcium concentration.
However, 40 to 45 percent of the calcium in serum is bound to
protein, principally albumin; as a result, increased protein binding
can cause an elevation in the serum total calcium concentration
without any rise in the serum ionized calcium concentration.
In addition, a single elevated serum calcium concentration should be
repeated to confirm the diagnosis. If available, previous values for
serum calcium should also be reviewed.

6. LABORATORY EXAMS
The initial goal of the laboratory evaluation is to differentiate
parathyroid hormone (PTH)-mediated hypercalcemia (primary
hyperparathyroidism and familial hyperparathyroid syndromes) from
non-PTH mediated hypercalcemia (primarily malignancy, vitamin D
intoxication, granulomatous disease)
 It is reasonable to order an intact PTH assay as part of the routine evaluation for
hypercalcemia even in a patient with known malignant disease.
 In the presence of low serum PTH concentrations (<20 pg/mL), PTH-related peptide
(PTHrp) and vitamin D metabolites should be measured to assess for hypercalcemia
of malignancy and vitamin D intoxication.

7. LABORATORY EXAMS
Ten to 20 percent of patients with primary hyperparathyroidism have
a serum PTH concentration in the upper end of the normal range
 Such a "normal" level (ie, not suppressed but not frankly elevated) is also virtually
diagnostic of primary hyperparathyroidism, since it is still inappropriately high
considering the presence of hypercalcemia.
 However, in this circumstance, the diagnosis of familial hypocalciuric hypercalcemia
also should be considered, and urinary calcium excretion (24 hour urinary calcium
or calcium to creatinine ratio) should be measured.

9. HYPERPARATHYROIDISM
The most common clinical presentation of primary
hyperparathyroidism (PHPT) is asymptomatic hypercalcemia.
 The diagnosis is usually first suspected because of the incidental finding of an
elevated serum calcium concentration on biochemical screening tests.
 In addition, PHPT may be suspected in a patient with nephrolithiasis.
PHPT is diagnosed by finding a frankly elevated parathyroid hormone
(PTH) concentration in a patient with hypercalcemia.
 When the PTH is only minimally elevated, or within the normal range (but
inappropriately normal given the patient's hypercalcemia), PHPT remains the most
likely diagnosis, although familial hypocalciuric hypercalcemia (FHH), a rare
disorder, is possible.

10. HYPERPARATHYROIDISM
Localization studies with ultrasonography, technetium-99m
sestamibi, computed tomography (CT), or magnetic resonance
imaging (MRI) scanning should not be used to establish the diagnosis
of PHPT or to determine management. If localization studies are
performed, they should be done after a decision for surgery has been
made.

15. ETIOLOGY
Single adenomas
 80 to 85 percent of cases
Multiple gland hyperplasia
 10 to 15 percent
Double adenomas
 2 to 5 percent
Parathyroid carcinoma
 1 percent
There is a relationship between iodine treatment as well as irradiation
and primary hyperparathyroidism

16. MANAGEMENT
Patients with symptomatic primary hyperparathyroidism (PHPT)
(nephrolithiasis, symptomatic hypercalcemia) should have parathyroid
surgery, which is the only definitive therapy.
For asymptomatic individuals who meet the Fourth International
Workshop on Asymptomatic Primary Hyperparathyroidism guidelines,
 surgery is indicated.
For asymptomatic individuals who do not meet surgical criteria,
 monitoring serum calcium and creatinine annually and bone density (hip, spine, and
forearm) every one to two years

18. BMD
IMPORTANCE OF RADIUS
EVALUATION

19. BMD
IMPORTANCE OF RADIUS
EVALUATION

20. BMD
IMPORTANCE OF TBS

21. BMD
IMPORTANCE OF TBS

22. PRE-OPERATIVE
LOCALIZATION
Preoperative parathyroid localization studies are useful for identifying
patients who are candidates for a minimally invasive surgical
approach.
Localization studies should not be used to diagnose or confirm the
diagnosis of primary hyperparathyroidism when positive, or to rule
out the diagnosis when negative.
 The diagnosis of primary hyperparathyroidism should be based upon biochemical
evaluation.
 Localization studies do not reliably exclude multiglandular parathyroid disease

23. PRE-OPERATIVE
LOCALIZATION
Can guide incision placement
Minimize the extent of surgical dissection
Identify concurrent thyroid pathology
Locate ectopic parathyroid tissue in patients with recurrent or
persistent hyperparathyroidism after unsuccessful parathyroid
exploration.

24. TC-99M MIBI SCINTIGRAPHY
A negative 99mTc sestamibi scan does not preclude the diagnosis of
primary hyperparathyroidism, since it occurs in 12 to 25 percent of
patients with disease
is often unrevealing in patients with parathyroid hyperplasia, multiple
parathyroid adenomas, and in those with coexisting thyroid disease
Falsely negative scans can also be caused by calcium channel
blockers that interfere with the take up of the isotope by parathyroid
cells
Other gland characteristics that can increase the likelihood of a
negative scan include small size, superior position, and a paucity of
oxyphil cells

25. SPECT
The multidimensional images illustrate the depth of the parathyroid
gland or glands in relation to the thyroid and improve detection of
ectopic glands which facilitates minimally invasive parathyroidectomy
substantially reduces the likelihood of missing multiglandular disease
compared to planar imaging
Because SPECT imaging has a high rate (7-16 percent) of missed
multiglandular disease, a validated adjunct to exclude multiglandular
disease such as intraoperative parathyroid hormone monitoring
should be routinely utilized.
SPECT-CT adds the ability to discriminate parathyroid adenomas from
other anatomic landmarks, which may facilitate the surgical
procedure

26. EXAMPLE OF AN ECTOPIC
PARATHYROID ADENOMA

27. IMPORTANCE OF SPECT/CT

28. IMPORTANCE OF SPECT/CT

29. IMPORTANCE OF SPECT/CT
MULTIPLE ADENOMA

30. IMPORTANCE OF SPECT/CT
MULTIPLE ADENOMA

31. IMPORTANCE OF SPECT/CT
MULTIPLE ADENOMA

32. SUBTRACTION TECHNIQUE
Even with the addition of SPECT, distinguishing abnormal parathyroid
glands from thyroid pathology can be difficult. If necessary, a
subtraction thyroid scan can be obtained by using two radiotracers
(dual isotope scintigraphy).
The use of technetium plus a second radiotracer such as 123I or
99mTc pertechnetate (thallium) permits selective imaging of the
thyroid gland.

33. SUBTRACTION TECHNIQUE
CASE 1

34. SUBTRACTION TECHNIQUE:
CASE 2
Tc-99m
MIBI early
Tc-99m
MIBI
Delayed
Tc-99m
Thyroid Scan

35. SUBTRACTION TECHNIQUE:
CASE 2

37. ULTRASONOGRAPHY
Sonographic characteristics of parathyroid adenomas include
homogeneous hypoechogenicity and an extrathyroidal feeding vessel
with peripheral vascularity seen on color Doppler imaging
US is highly sensitive in experienced hands and is inexpensive,
noninvasive, and reproducible in the operating room.
As with sestamibi based techniques, the sensitivity of ultrasound for
parathyroid adenoma localization is reduced in patients with thyroid
nodules

38. UTRASONOGRAPHY
Most experts in parathyroid surgery rely on both US and SPECT for
preoperative localization
Combining 99mTc-sestamibi scintigraphy with neck ultrasound
provides high sensitivity (79 to 95 percent) for predicting the location
of a single parathyroid adenoma
No imaging technique, even in combination, accurately predicts
multiglandular disease, and a bilateral neck exploration should be
strongly considered when the studies are discordant, equivocal, or
negative
Disadvantages to the use of US alone include decreased accuracy in
patients with smaller parathyroid gland size, obesity, or mediastinal
glands located behind the clavicles

41. FOUR DIMENSIONAL
COMPUTED TOMOGRAPHY
take advantage of the rapid contrast uptake and washout that is
characteristic of parathyroid adenomas for precise anatomic
localization
4D-CT is particularly useful in the reoperative setting when initial
imaging with sestamibi is negative
The primary disadvantage of 4D-CT is the radiation exposure, which,
compared with sestamibi imaging, results in a >50-fold higher dose
of radiation absorbed by the thyroid.

43. MAGNETIC RESONANCE
IMAGING
Parathyroid adenoma characteristics on magnetic resonance imaging
(MRI) include intermediate to low signal intensity on T1 imaging and
high intensity on T2 imaging. Cervical lymph nodes can also have
similar imaging characteristics, which limit the accuracy of MRI.
The reported sensitivity of MRI for abnormal parathyroid tissue
ranges from 40 to 85 percent

44. POSITRON EMISSION
TOMOGRAPHY AND CT
The combination of 11C-methionine positron emission tomography
and computed tomography (MET-PET-CT) uses 11C-methionine as a
radiotracer to identify pathologic parathyroid glands
A prospective study that included 102 patients undergoing a
parathyroidectomy for primary hyperparathyroidism found that MET-
PET-CT scan correctly located a single gland adenoma in 83 of 97
patients (86 percent), with a positive predictive value of 93 percent

45. INVASIVE LOCALIZATION
Invasive procedures, such as selective venous sampling or selective
arteriography, are generally reserved for more definitive localization
in patients who have had prior neck surgery and in whom noninvasive
testing has been unrevealing.
They may also be used in a primary operation for the patient in whom
noninvasive techniques are equivocal or unrevealing, but enthusiasm
for their use is tempered by risks associated with the procedures

46. NEGATIVE IMAGING
should not preclude initial surgery
 In such patients, a single adenoma is still the most likely intraoperative finding (62
to 77 percent); however, multiglandular disease is also common (20 to 38 percent).
 These patients require bilateral exploration by an experienced parathyroid surgeon
 When compared to patients with localized studies, equivalent long-term
biochemical cure rates can be achieved although more extensive surgery may be
needed
In the reoperative setting, negative sestamibi and ultrasound results
usually lead to prompt use of additional noninvasive imaging
modalities such as 4D-CT and/or MRI.
 If these studies are also non-localizing, then invasive studies such as arteriography
or selective venous sampling can be performed.
 Reoperation with negative imaging is associated with a high failure rate (up to 50
percent) and nonoperative medical management should be considered

49. PARATHYROID EXPLORATION
Parathyroidectomy provides definitive therapy for PHPT and is
performed for
 all patients with symptomatic disease
 patients with familial disease
 patients with asymptomatic disease who have decreased glomerular filtration rates,
osteoporosis, serum calcium >1 mg/dL above normal, or age less than 50 years.
 parathyroid cancer
 parathyroid crisis
 for selected patients with persistent or recurrent primary hyperparathyroidism.

53. PARATHYROID SURGERY
Contra-indications
 Absolute
 familial hypocalciuric hypercalcemia
 Relative
 Contralateral recurrent laryngeal nerve injury
 symptomatic cervical disc disease

54. MINIMALLY INVASIVE
APPROACH
Including
 endoscopic and video assisted approach + intra-operative PTH monitoring
 Radioguided parathyroidectomy using a gamma probe
Best reserved for
 patients who have unilateral pathology as detected by imaging,
 without thyroid disease
 with no family history of multiple endocrine neoplasia
 No evidence of parathyroid carcinoma

55. INTRA-OPERATIVE
MONITORING
Intraoperative parathyroid hormone monitoring
 A reduction of at least 50 percent from the baseline following excision of the
hyperfunctioning gland is an accepted standard for intraoperative confirmation of
success
 False-positive intraoperative PTH findings (defined as a >50 percent decrease)
followed by recurrent hyperparathyroidism should raise suspicion for a multiple
endocrine neoplasia (MEN) syndrome.

56. INTRA-OPERATIVE
MONITORING
Radioguided parathyroidectomy
 The use of a radioguided probe has been advocated by some to serve as a useful
adjunct in parathyroid exploration. The technique involves intravenous
administration of technetium-99m labeled sestamibi approximately two hours
preoperatively
 Using sestamibi uptake as an indirect measure of parathyroid gland hyperfunction,
the surgeon uses a handheld gamma probe in conjunction with preoperative
imaging results to focus the incision over the site of greatest radioactivity
 Once the suspected offending gland or glands are removed, intraoperative PTH
monitoring is utilized to confirm adenoma excision of identify multiglandular
disease, and the gamma probe is also used to survey the surgical bed.
 An ex vivo radioactivity count >20 percent above background is a possible
threshold for completion of the exploration

57. BILATERAL NECK
EXPLORATION
Should be considered for the following patients
 patients with negative (non-localizing) preoperative imaging studies or when
bilateral foci are detected
 Most forms of hereditary hyperparathyroidism
 Concomitant thyroid disease requiring surgical resection
 Lithium associated hyperparathyroidism
Normal parathyroid tissue should not be removed. If PTH does not
decrease, auto-transplantation should be considered.

58. PARATHYROID CARCINOMA
Rare cause of primary hyperparathyroidism.
Is difficult to distinguish from parathyroid adenoma based on preoperative
evaluation
 May be suggested by
 A solitary tumor greater than 3 cm in diameter.
 A firm, irregular, lobulated mass.
 A dense, fibrous capsule surrounding the tumor producing a white or gray-brown tint.
 Invasion of, or adhesion to, surrounding structures
 Lymph node metastasis (present in 3 to 19 percent of parathyroid cancer cases).
 Cystic features.
The presence of these operative findings in patients with preoperative
calcium levels greater than 14 mg/dL,and parathyroid hormone levels
greater than three times the normal value, are highly suggestive of
parathyroid carcinoma

59. PARATHYROID CARCINOMA
Patients suspected of parathyroid carcinoma should undergo an en-
bloc resection of the parathyroid tumor with the ipsilateral thyroid
lobe and isthmus, and a central neck dissection (level VI).
It is important to avoid capsular violation or tumor spillage (eg, with
biopsy).
A modified lateral neck dissection is not required in the absence of
clinical nodal involvement

60. PARATHYROID CARCINOMA:
CASE

61. PARATHYROID CARCINOMA

62. PARATHYROID CYSTS
Parathyroid cysts are uncommon, but can cause severe hypercalcemia
and other symptoms.
If noted before surgery, the cyst fluid should be aspirated for PTH
assay. The optimal treatment is surgical resection. Meticulous
dissection should be employed to avoid cyst rupture because this can
lead to elevated intraoperative PTH levels which may prolong the
surgical procedure

63. A CASE OF A PARATHYROID
CYST PROVED TO BE
PARATHYROID CARCINOMA

64. SECONDARY
HYPERPARATHYROIDM
Pre-operative localization is not widely used as bilateral neck
dissection is used.

65. SENSITIVITY OF PLANAR
SESTAMIBI IMAGING

66. SPECIFICITY OF PLANAR
SESTAMIBI IMAGING

67. CLINICAL VALUE OF IMAGING
some noteworthy information can be obtained by performing 99mTc-
MIBI parathyroid scintigraphy in SHPT
 detection of ectopic glands (pre-operative map) thus avoiding surgical failure or
reducing the extent of dissection
 identification of an eventual supernumerary fifth gland (present in 10 % of
individuals and frequent cause of persistence/recurrence)
 identification of the parathyroid gland with the lowest 99mTc-MIBI uptake intensity,
intended to be partially autografted or maintained.

68. PARATHYROID HYPERPLASIA
CASE

69. PARATHYROID HYPERPLASIA
CASE