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

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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

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

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

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

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

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

Pathophysiology Primary hyperparathyroidism ↑ Ca++ ↑ PTH Typically seen in 50-70 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

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%)

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

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

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.

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.

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).

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

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

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.

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

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

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

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.

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

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

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

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

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