PARATHYROID IMAGING. James Lee, MD Chief, Endocrine Surgery Co-Director NY Thyroid-Parathyroid Center Columbia University Medical Center

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PARATHYROID IMAGING James Lee, MD Chief, Endocrine Surgery Co-Director NY Thyroid-Parathyroid Center Columbia University Medical Center

NO DISCLOSURES

Overview The hallmarks of the ideal test Benefits and Limitations MRI USG Sestamibi Scan 4D CT Parathyroid FNAB with PTH washout Selective Venous Sampling Combined USG and MIBI Special Cases Reoperative Secondary Hyperparathyroidism MEN 1

The only localizing study indicated is to localize an experienced parathyroid surgeon John Doppman, 1986

The goal of localizing studies is to limit the amount of pain for the patient and surgeon

Ectopic Locations

Hallmarks of the ideal test Localize culprit gland Size vs Function Provide a roadmap of where to look Identify normal glands Identify associated thyroid disease Minimize radiation

Interpreting results What is success (i.e. true positive)? Localizes to gland vs quadrant of neck vs side? Positive predictive value Likelihood that an identified adenoma will actually be there True negative can be as important as the true positive Surgeon review is more accurate than radiologist Sensitivity of MIBI when read by High volume Radiologist = 75-83% Low volume Radiologist = 72% Surgeon = 86-93% ALWAYS LOOK AT THE IMAGES YOURSELF

Kuntsman, et al. JCEM 98(3):902-12

MRI

MRI Terrible test for parathyroid disease 59% sensitivity for glands in normal position and 79% for ectopic glands False positives: thyroid nodules and lymph nodes Benefits: Typically reserved for re-operative cases or to confirm mediastinal adenomas Limitations: Expensive, poor sensitivity, patient compliance

Kuntsman, et al. JCEM 98(3):902-12

USG

Sagittal Transverse

Ultrasound 70-80% sensitivity False positive: thyroid nodules, lymph nodes Benefits: Fast, office-based No radiation FNA-PTH sampling Can delineate intrathyroidal glands Best for looking at thyroid Limitations: Operator dependent Cannot penetrate bone/air Not good for retroesophageal, retrosternal, retrotracheal, deep cervical Can t see mediastinal glands Usually miss small glands Typically can t see normal glands

Surgeon-performed USG Over 100 studies to date Higher diagnostic rate More useful description of locations Increased accuracy

Kuntsman, et al. JCEM 98(3):902-12

SESTAMIBI

Sestamibi Concentrates in mitochondria Parathyroid, thyroid, salivary glands, heart Longer time to wash out of parathyroid then thyroid Adenomas have higher percent of oxyphil cells Types: Delayed Dual Isotope SPECT-CT

Delayed Technique

Dual-Isotope Technique Early Sestamibi

Dual isotope protocol 123 I

Dual isotope subtraction protocol Early MIBI 123 I (MIBI - 123 I) _ =

Dual isotope subtraction protocol Early MIBI 123 I (MIBI - 123 I) subtraction _ = Delayed MIBI

Delayed and Subtraction

False Positive

Follicular and Hurthle Cell Neoplasms

Utility of SPECT I-123 Early MIBI Delayed MIBI

Multi-gland Disease 600mg 1400mg RAI Sestamibi 123 I Early MIBI Delayed MIBI

4 gland hyperplasia

The negative MIBI Refer to a high volume center High volume centers have better localization (82% vs 67%) Negative MIBI will be positive if repeated at high volume center in many cases (up to 80%) Get a 4D CT

Sestamibi 80-90% sensitivity for single adenomas depending on the technique and local expertise Must at least do delayed images Subtraction Pro: 5-10% higher sensitivity Con: may be affected by thyroid replacement/recent iodine loads Thyroid nodule that is MIBI+/cold on RAI, has 47% PPV and 88% specificity for thyroid cancer SPECT is particularly useful in imaging ectopic adenomas (mediastinal or deep in neck) False negative: cystic adenomas, multigland disease

Sestamibi (cont d) Benefits: Good sensitivity Identifies ectopic glands (especially mediastinal and undescended) Functional test, not just anatomic Acceptable radiation Limitations: Only 35% accurate in multiple gland disease Quality is highly variable Small glands Does not provide precise anatomic detail Usually miss small glands

Kuntsman, et al. JCEM 98(3):902-12

COMBINING USG/MIBI

Combining USG and MIBI Kebebew Score: 1 point each for calcium >12, PTH > 2x ULN, positive MIBI, positive USG, concordant MIBI and USG Kebebew E, et al. Arch Surg 141(8):777-782, 2006. Concordant MIBI and USG = 96% chance that is the only abnormal gland Arici C, et al. Surgery 129(6): 720-9, 2011

Positive MIBI/Negative USG 58% chance of PLUG (posterior located upper gland) USG cannot visualize past trachea Harari et al. Ann Surg Oncol 18(6):17171-22, 2011

4D CT

Rodgers SE et al. Surgery 2006. 140:932-941.

4D CT Very thin cuts 4 th dimension is time i.e. contrast characteristics over time Adenoma <80HU on non-contrast >130HU at 45s Decrease by >20HU on delayed images Lymph node Start at soft tissue density, increase to peak<130 and increase further on delayed images Different protocols perform different # of scans Non-contrast Arterial phase (25s) Washout 1 (30s) Washout 2 (60-75s)

Precise Information Provided by High Quality CT Scanning A 0.4cm AP and 0.7m wide and nearly 1.8cm long (262ml) moderately hypervascular nodule, located at the posteriomedial aspect of the right mid-lower thyroid lobe, behind the neurovascular bundle, directly anterior to the right longus colli muscle, medial to the right common carotid artery and just to the right of the esophagus, is consistent with a low-lying right upper parathyroid adenoma with an estimated weight of 262mg At surgery, the above was confirmed, wt 300mg.

Highly accurate in setting of negative MIBI 85% sensitive, 94% specific in lateralizing 66% sensitive, 89% specific in predicting exact location Harari A, et al. Surgery 144(6):970-6, 2008

Visualization of Normal Parathyroid

4D CT 90% sensitivity, 93-95% PPV False positive: lymph nodes Benefits: Precise anatomic localization Some functional information Can visualize normal parathyroid gland 100% specificity for multigland disease Limitations: Needs a dedicated radiologist Radiation

Kuntsman, et al. JCEM 98(3):902-12

PARATHYROID FNAB

Intrathyroidal gland

FNAB and PTH Washout Cytology may resemble follicular lesion Must do PTH washout Benefits: Excellent PPV Functional data Can distinguish between parathyroid and thyroid Limitations: May make surgery more difficult

Kuntsman, et al. JCEM 98(3):902-12

SELECTIVE VENOUS SAMPLING

Selective Venous Sampling Sensitivity 70-80% Benefits: Functional data Good for mediastinal and cervical adenomas May identify multigland disease Limitations: Invasive (risks of embolization, bleeding, hematoma, etc) Radiation Cannot use in renal failure patients Does not provide precise anatomic detail Requires a high degree of expertise

Kuntsman, et al. JCEM 98(3):902-12

RE-OPERATIVE CASES

Re-operative Cases Confirm the diagnosis Rule out BFHH with 24 hour urine Goal is a minimally invasive operation Localize with at least 2 modalities 4D CT highly accurate Sensitivity 88% vs 54% with MIBI Accuracy ~82% Consider FNAB with PTH washout

SECONDARY HYPERPARATHYROIDISM

Secondary Hyperparathyroidism 15% have supernumerary glands Often in thyrothymic ligament Rule out mediastinal disease

MEN 1

MEN 1 4 gland exploration is near-mandatory Imaging may make the exploration easier Rule out mediastinal disease/thymic carcinoma

Take home points Good parathyroid imaging can make life easier for everyone 4D CT is the most accurate localizing test In re-operative cases Localize with 2 modalities Consider FNAB, selective venous sampling if other modalities fail

THANK YOU

ECTOPIC LOCATIONS

Typical lower- sestamibi

Lower gland in thyrothymic ligament- USG

Lower gland in thyrothymic ligament-sestamibi

PLUG- MIBI

Mediastinum