1. Unlocking the Parathyroid Puzzle: A Detailed Look at the Multimodality Options
Faulkner, A. Gibbs, w.
EEDE-168

2. No disclosures

3. Educational Objectives
Increase your knowledge of the relevant anatomy and pathophysiology of hyperparathyroidism
Discover the multimodality imaging options for evaluating hyperparathyroidism:
Sestamibi scintigraphy
4D CT
Ultrasound
MRI

4. Embryology Typically 2 superior and 2 inferior glands Superior glands
Derived from 4th pharyngeal (brachial) pouch along with the lateral thyroid lobes
Inferior glands
Derived from 3rd pharyngeal (brachial) pouch along with the thymus

5. Anatomy Superior gland More consistent location
90% located deep to mid portion of the superior pole of the thyroid lobe
4% deep to mid pole, 3% at or above most superior point 1% retropharyngeal, 1% retroesophageal, <1% intrathryoidal

6. Anatomy Inferior gland More variable location
69% inferior, posterior or lateral to lower thyroid pole
26% along the course of the thymus from lower neck to cervical portion of thymus
2% anterior mediastinum with the thymus or inferior to the thymus <1%
Rarely cranial to the superior glands

7. Anatomy Average size 5 x 3 x 1 mm Average weight 40-50 grams
Adenoma mass greater than 10 times normal
Hyperplastic glands of variable size/weight

8. Pathophysiology Produce parathyroid hormone (PTH)
Increases calcium level by
↑ renal tubular absorption of calcium
↓ tubular reabsorption of phosphate
↑ osteoclasts
↑ Vit D production → ↑ GI absorption of calcium

9. Pathophysiology Primary hyperparathyroidism ↑ Ca++ ↑ PTH
Typically seen in year old patients
F>M
89% single adenoma
6% hyperplasia of all 4 glands
4% double adenoma
Increased incidence in MEN I and MEN IIA

10. Treatment
The trend of utilizing minimally invasive parathyroidectomy with resultant cure rate of 99.4% (complication rate 1.45%) puts greater emphasis on accurate pre-operative localization as opposed to conventional exploration with bilateral cervical dissection (cure rate 97.1% and complication rate 3.1%)

11. What are the options for pre-operative localization?
Nuclear medicine Sestamibi scintigraphy
Ultrasound
Grey scale
Contrast-enhanced
4D CT
MRI

12. What are the options for pre-operative localization?
Sestamibi and ultrasound
Similar sensitivities and specificities for solitary adenoma detection individually
Most commonly used imagining techniques currently employed
4D CT and MRI
Typically used after failed parathyroidectomy or discordance between sestamibi and ultrasound

13. Sestamibi Scintigraphy
A meta-analysis of 20,225 cases of primary hyperparathyroidism reported 99mTc sestamibi was: 88.44% sensitive for solitary adenoma, 44.46% for multiple gland hyperplasia, and 29.95% for double adenoma. 
99mTc Sestamibi taken up by normal thyroid and parathyroid glands, with more avid and prolonged retention in parathyroid adenomas and parathyroid hyperplasia
Improvement in visualization using delayed 2 hour technique, SPECT, subtraction of 99mTc pertechnetate which is only taken up by the thyroid gland
Limited scintigraphic resolution for smaller adenomas <500 grams
Few studies have shown little benefit with combination with SPECT/CT with exception to localization of ectopic parathyroid glands.

14. Sestamibi Scintigraphy
Pertechnetate image (top left) demonstrates uptake in expected physiologic locations including the thyroid gland. Sestamibi images taken every ten minutes for one hour demonstrate a focus of tracer uptake below the inferior pole of the left thyroid lobe compatible with a parathyroid adenoma. Appreciate the prolonged retention of the sestamibi in the parathyroid adenoma relative to the thyroid gland.

15. Sestamibi Scintigraphy
Pertechnetate image (top left) in Patient X demonstrates uptake in expected physiologic locations including the thyroid gland. Sestamibi images demonstrate a focus of tracer uptake below the inferior pole of the left thyroid lobe compatible with a parathyroid adenoma (white arrow). Notice the physiologic cardiac uptake on the sestamibi images (yellow arrow).

16. Ultrasound
Traditional grey scale and color Doppler sensitivities reportedly 78% for single adenomas, 16% for double adenomas, and 35% for multiple-gland hyperplasia 
Solitary adenoma - Homogeneous, hypoechoic, hypervascular mass
Cervical lymph node often mimics parathyroid adenoma
Hyperplasia more difficult to visualize given smaller size
Ectopic location in mediastinum or retrotracheal adenoma difficult to detect
Peripheral rim of vascularity on color Doppler - extrathyroidal feeding vessel (typically inferior thyroidal artery branch), which enters the pole of the parathyroid adenoma

17. Ultrasound
Grey scale sonographic images demonstrate an oval, hypoechoic mass posterior to the right thyroid lobe compatible with a pathologically proven parathyroid adenoma.

18. Ultrasound
Gray scale (left) and color Doppler (right) in long (top) and transverse (bottom) dimensions demonstrate an oval hypoechoic mass with feeding vessel entering at the pole with peripheral arc of increased vascularity located inferior to the left thyroid lobe. Notice the lack of fatty hilum and central feeding artery which would be seen in a lymph node.

19. Contrast-Enhanced Ultrasound
Early European studies demonstrate improved sensitivity and specificity in confirming suspected adenomas
CEUS utilizes a non-nephrotoxic perfluoro microbubble contrast agent
Adenomas demonstrate early arterial enhancement with late phase washout
Improved differentiation between parathyroid adenomas and thyroid nodules or lymph nodes

20. Contrast Enhanced Ultrasound
Hypoechoic parathyroid adenoma on grey scale ultrasound (left) demonstrating homogeneous arterial enhancement after contrast administration (right).

21. 4D CT
3 dimensions: Multiplanar axial CT with coronal and sagittal reformats
4th dimension: time – change in enhancement over time in non- contrast, arterial and delayed venous phases
Investigate arterial phase for eutopic or ectopic suspicious lesions
Review all phases for:
Noncontrast – density lower than thyroid gland
Arterial phase – avid enhancement
Delayed phase – rapid washout
High accuracy for single and multigland detection

22. 4D CT
Noncontrast (left), arterial phase (middle) and delayed phase (right) axial images through the thyroid gland demonstrate a soft tissue density nodule located posterior to the right thyroid gland that enhances on arterial images and exhibits wash out on delayed images.

23. MRI Similar sensitivity compared to other imaging modalities
Compared to normal thyroid, parathyroid adenomas are:
T1 iso to hypointense
T2 hyperintense
Often enhance
Enhancement increases sensitivity of atypical T1 and T2 isointense adenoma detection
Pitfall – lymph nodes have similar signal characteristics

24. MRI
Axial T2, T1 and T1 FS Post contrast images (top) demonstrate a T2 hyperintense, T1 isointense, enhancing parathyroid adenoma in the left anterior mediastinum, inferior to the left thyroid lobe

25. MRI
Axial T2, T1 and T1 FS Post contrast images (top three) and coronal T1 FS Post contrast (top right) and coronal T2 (bottom right) demonstrate a T2 hyperintense, T1 isointense, enhancing parathyroid adenoma inferior to the left thyroid lobe

26. Summary
Traditionally used methods - Sestamibi scintigraphy and ultrasound – remain first line imaging modalities
4D-CT shows great promise, and there is increasing utilization of this modality
There is a potential future role for contrast-enhanced ultrasound, which will improve sensitivity and specificity when added to grey scale and color Doppler ultrasound

27. References
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Agha A, Hornung M, Stroszcyznski C et al. Highly Efficient Localization of Pathological Glands in Primary Hyperparathyroidism Using Contrast-Enhanced Ultrasonography (CEUS) in Comparison With Conventional Ultrasonography. J Clin Endocrinol Metab, 2013, 98 (5);
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