1. IMAGING OF PARATHYROID DISEASE : A GUIDE FOR THE REFERRING PHYSICIAN
Maroun Karam MD FACP
Professor of Radiology and Nuclear Medicine

2. Nuclear Imaging of Hyperparathyroidism
Parathyroid imaging
- The clinical problem
- Facts about Tc Sestamibi
- When to order scintigraphy ?
- Protocol for dual-phase imaging
- Radiopharmaceutical
- Imaging technique
- Dual tracer imaging
- Illustrative cases
- How does it compare to ultrasound?
- How to improve results
- Practical recommendations

3. PREOPERATIVE IMAGING OF PARATHYROID LESIONS .
Was rarely performed because
1111. Intraoperative localization by experienced surgeon in % (Bilateral neck exploration)
2. Recent increase in preoperative imaging because
- Not all surgeries are performed by experienced surgeons.
- There is increased interest in less invasive surgery
- Unilateral neck exploration (UNE)
- Minimally invasive parathyroidectomy (MIP)
3. Bilateral neck exploration is still required if there is hyperplasia or suspected multigland disease
-Recent survey: less invasive surgery by >50% of surgeons worldwide.
3. If there is, bilateral neck exploration is still required.

4. PERSISTENT HYPERPARATHYROIDISM
Continuation of calcium abnormalities immediately after surgery
Was the ONLY indication for scintigraphy before MIP
Occurs in 7-10% of all patients who undergo surgery.
Causes:
- Failure to localize the adenoma (ectopic): frequent
- Inadequate resection of multigland disease.
- Surgical inexperience.
- Metastatic parathyroid carcinoma ( very rare)
More frequent in familial syndromes (20-50%)

5. Some Facts About Tc Sestamibi
Not specific for parathyroid tissue.
High uptake in cells with increased metabolism and high number of mitochondria (parathyroid and thyroid adenomas), uptake 2.5 times background
Limited performance in parathyroid hyperplasia ( 50-60% detection rate ) because hyperplasia is a different disease with
fewer active mitochondria ( uptake is 1.2 times background )

6. TECHNIQUE OF DUAL PHASE IMAGING
Easiest to perform and most commonly used
Injection of 25 mci of Tc Sestamibi
3. Immediate visualisation of thyroid tissue and abnormal parathyroid tissue
Progressive washout of tracer from the thyroid and persistent uptake in abnormal parathyroid glands
False positive: thyroid adenoma can be eliminated by the performance of a neck ultrasound or exam prior to nuclear imaging in pts with hyperpara
False negative : small or not metabolically active parathyroid adenomas(10%)
EQUIVOCAL : DELAYED OR INCOMPLETE WASHOUT FROM THE THYROID MAY NOT ALLOW DETECTION OF ADENOMA .

7. EASY TEXTBOOK CASE UNFORTUNATELY NOT ALL CASES ARE LIKE THIS ONE

9. FALSE POSITIVE: Thyroid adenoma
FALSE POSITIVE: Thyroid adenoma . It is important to perform a rapid neck EXAM
Before sending pt to scintigraphy. If there is a thyroid nodule, info should be put
on the request , indicating location of nodule

10. 2 hr planar
10 min planar
DELAYED IMAGE
EARLY IMAGE
VERY SMALL ADENOMA ALMOST A FALSE NEGATIVE
IT IS BEST TO HAVE PTH TWICE NORMAL BEFORE REQUESTING IMAGING
Most common cause of false negative : small adenomas that are only
seen on the early planar images

11. Identification of a persistent focus requires that
The tracer washes out from the thyroid
The report will say : On delayed imaging
No persistent focus of activity was seen
Did you know that the pattern above is
one common reason for the reported result ?

12. WHY DELAYED OR INCOMPLETE THYROID WASHOUT?
Preparation consists of a mixture of Tc MIBI and free Tc
Residence of MIBI in the thyroid gland is min
Residence of free Tc is min
If percentage of Tc is > 5% incomplete washout can happen preventing detection of parathyroid adenoma
Current commercial preps have 10% of free TC . This is adequate for cardiac imaging but is NOT for parathyroid
NEED TO INCREASE PURITY OF MIBI COMMERCIAL PREPARATIONS FOR PARATHYROID IMAGING

13. Purity =90% Delayed image : 2 hrs Early image : 20 min
No adenoma identified
Early image : 20 min
Purity =90%

14. SAME PT AFTER INCREASING PURITY TO 95%

15. This pt had a neg study with
90% purity prep at another hospital
Repeat Study at AMC with 97% purity
Was positive for right lower adenoma

16. Radiochemical Purity of Current Technetium 99m Sestamibi Commercial Preparations May Not Be Adequate for Dual-phase Parathyroid Imaging.
M. Karam, R Dansereau, P Feustel , M Mecca, L Robinson
Albany Medical College Department of Radiology Division of Nuclear Medicine
“Nuclear medicine Communications”2005 p 1093

17. HOW IS THE SITUATION DIFFERENT IN LEBANON FROM THE US
In the US radiotracers are delivered as individual doses by central pharmacies
When we have to do a parathyroid scan we have to indicate it on request
The central pharmacy will change the method of preparation to obtain higher purity
In Lebanon we don’t have central commercial pharmacies . The nuc med tech prepares the tracer
I have learned from R Dansereau PhD how to improve purity and I have taught the tech here

18. PARATHYROID SCINTIGRAPHY RESULTS
Single Gland disease
Sens : 90%.
FN most often when small or mildly metabolically active adenoma ( SPECT)
Multigland disease
Sens : overall 60% and related to number of glands
2 glands: 79%
3 glands: 64%
4 glands: 40%

19. PRIMARY HYPERPARATHYROIDISM
-Mostly women and elderly : 1-2/1000 of routine blood screening. Explains significant rise in incidence
SPORADIC DISEASE
1. Adenomas or single gland disease: 80-85%* 5 % of adenomas are bilateral
2. Hyperplasia or multigland disease: 15-20%*
% of adenomas are ectopically located (15% in the neck, 2-5% in the chest)MOST ECTOPIC ADENOMAS ARE IN THE NECK AND OUT OF THE US FIELD
4. Only 60% of inferior adenomas are adjacent to inferior pole . 40% of inferior adenomas are ectopic at base of the neck
5. Supernumerous (> 4) glands in 2-5% of the population.
FAMILIAL SYNDROMES
Associated with multigland disease as a rule.
1. MEN-1 (85-90%)
2. MEN-2 (5-10%)
3. Other.
*Histopathologic criteria to distinguish adenoma from hyperplasia are not defined.
Adenoma= single gland disease. Hyperplasia=multigland disease.

20. Non-Primary Hyperparathyroidisnm
Secondary ( CRF) : Always hyperplasia
Tertiary: -Uncommon.
-Occurs after prolonged secondary.
-Can be adenoma on hyperplasia

21. PRACTICAL CONCLUSIONS FOR THE REFERRING PHYSICIAN.
11 Rule out secondary hyperparathyroidism.
2. Rule out thyroid focal pathology.
- Exam
- Ultrasound
- If positive →Info provided on prescription
3. Family history (-) MEN (-)
- high likelihood of adenoma ( 85%)
- Imaging very helpful
-If (+) Consider unilateral neck exploration .
4. Family history (+) or MEN (+)
- Bilateral neck exploration is required.
-Imaging not necessary unless persistent hyperparathyroidism.
5. Suspect tertiary hyperpara  imaging can be helpful

22. How to Improve Imaging Results
Neck examination before every scan and write down findings on requisition ( thyroid nodules > 1 cm ). If ultrasound performed first , please write results if thyroid nodule on scinti request .
It is a must to use pinhole collimator for planar neck images ( improves detection from 60 to 75%)
SPECT
- improves sensitivity from 75 to 85%
- Provides exact location of adenoma allowing smaller incision and shorter operative time ( local anesthesia ? )
SPECT/CT has been shown to be superior to SPECT if the adenoma is extra cervical
* Lavely et al J. Nuc Med ,

23. Bilateral adenoma

24. WHERE IS THE ADENOMA ? LEFT OR RIGHT ?
NEED SPECT IMAGING TO DETERMINE SIDE

25. RIGHT ANTERIOR PARATHYROID ADENOMA

26. THE ADENOMA IS
IMMEDIATELY
BELOW LOWER POLE
OF LEFT LOBE

27. Cervical
But ectopic
Parathyroid
Adenoma , very
Difficult to detect
By ultrasound

28. THIS ADENOMA
IS INTRATHROIDAL

29. Superior
Mediastinal
Adenoma

30. Only situation where SPECT/CT Found to be superior to SPECT*
Mediastinal adenoma
Only situation where SPECT/CT
Found to be superior to SPECT*
* Gayed et al J. Nuc Med, 46,

31. SPECT/CT IN PARATHYROID IMAGING
WILL BECOME AVAILABLE AT ST GEORGE HOSPITAL IN JUNE 2017

32. SPECT/CT IN PARATHYROID IMAGING

33. SPECT/CT IN PARATHYROID IMAGING

34. DUAL TRACER IMAGING IMPROVES SENSITIVITY FROM 83 TO 87% ONLY
substraction
Reserved
For negative
Dual tracer or
Imaging of
persistent
Disease
Or if there is a thyroid
nodule
DUAL TRACER IMAGING IMPROVES SENSITIVITY FROM 83 TO 87% ONLY

35. DUAL TRACER IMAGING : PROS AND CONS
Advantages ;
Allows to exclude thyroid pathology as cause of false positive
Improves reader confidence
Disadvantages
1 . Is time consuming and expensive ( 2 tracers + 2 scintigraphies )
2 . Requires complete neck immobilization and patient cooperation
3 Neck motion will introduce false positive or false negative findings
DUAL TRACER IMAGING IMPROVES SENSITIVITY FROM 83 TO 87% ONLY
IF HIGH PURITY AND SPECT ARE USED

36. Comparative Performance of Parathyroid scan and US
Ultrasound: Variable sensitivity depending on series ( 53%-78%) Specificity HIGH at 96%
Meta-analysis of US in 1523 cases : Sens 69%
Dual Phase imaging of primary sporadic hyperparathyroidism. Sens : %, specificity 95% = narrow range of sensitivity if experienced nuclear medicine physician
Very wide range of sensitivity for US suggests that it is operator dependent .Opposite true for NM
NM results are better overall than best US operator but they also require excellent technique and expert reader
( AUB experience: NM 91%, US 73% on same pts , World J Surg, 2006)
Sestamibi nuclear scan is the test of choice for persistent HP because of high incidence of ectopic adenoma. Same reason applies for negative ultrasounds

37. US vs NM for HP ( 2)
All studies show superior performance of NM vs US in ectopic glands (80 vs 25%)
Ectopic gland is the most common cause of persistent hyperparathyroidism
Almost all studies show both methods are poor for hyperplasia and multigland disease no need for imaging
US more convenient to the pt ( brief exam ) if operator is skilled
All studies show that accuracy decreases in the presence of thyroid disease
Most studies show , that when one is negative, the other is often positive ( combined sens : 95%)

38. PRACTICAL RECOMMENDATIONS
Secondary Hyperparathyroidism (HP) or familial syndromes : Bilateral neck exploration
Persistent hyperparathyroidism : Tc Sestamibi scan FIRST because of high likelihood of ectopic
disease. If scan negative , can perform intraoperative localization after tracer administration
3. Sporadic primary HP : Start with the imaging method provided by an available expert
4. If starting with NM scan , thorough neck examination, looking for thyroid nodule
5. If thyroid nodule > 1 cm present, make note on requisition of nodule location
6. If first imaging method is negative , proceed to the second.
7. Even in the best hands , sensitivity of ultrasound is lower than NM scan ( ectopic)
8. If both imaging methods are negative, or equivocal bilateral neck exploration

39. HOW TO IMPROVE SURGICAL RESULTS
Intraoperative measurement of PTH before and after resection of lesion*
↓50% or more in value is required (PTH T1/2=2-3min)
↑Sens for detection of multigland disease from 23 to 88%
Sens: 98%, Spec: 94% Accuracy: 97% in predicting surgical success.
More recent results reported not to be as good
*Bergson et al Arch Otol Head Neck Surg 130(1)

40. CONCLUSIONS (1)
Since MIS , preoperative parathyroid imaging has become necessary. It is best to have a PTH twice normal before imaging unless immediate surgery is necessary because imaging yield increase with high PTH
It is important first to establish primary etiology ( or tertiary)
If familial syndromes or secondary , NO IMAGING BECAUSE BILATERAL
US is very operator dependent but gives OK results in good hands
NM is the imaging of choice for persistent hyperpara because most common cause is ectopic adenoma

41. CONCLUSIONS (2)
HIGH purity of preparation is essential . If provided dual tracer imaging is ONLY marginally better than dual phase imaging
SPECT has improved results and allows exact localization of adenoma for surgeon ( smaller incision , shorter operative time)
SPECT/CT helpful for extra-cervical adenomas
Intraoperative PTH has improved surgical results
An experienced surgeon remains important