Pre-operative localization of parathyroid adenoma Dr Chan Man-yi Tuen Mun Hospital

Primary hyperparathyroidism Gold standard = bilateral neck exploration 95 – 98% at first exploration Imaging used only after failed initial surgery Identify all 4 parathyroid glands, remove abnormal gland(s) Solitary adenoma – all 4 glands sampled, adenomatous gland removed Hyperplasia – subtotal 3.5 gland resection with cryopreservation or total parathyroidectomy with autotransplantation into forearm / neck muscle Carcinoma – radical removal including ipsilateral LN and ipsilateral thyroid 70 – 90% at re-exploration

Etiology of primary hyperparathyroidism Solitary parathyroid adenoma 80-85% Unilateral neck exploration Minimally invasive surgery Foscused parathyroidectomy Video-assisted parathyroidectomy Videoscopic parathyroidectomy Multiple parathyroid adenoma 2-3 % Diffuse hyperplasia 10-15% Parathyroid carcinoma 2-3% Minimally invasive surgery Unilateral neck exploration Foscused parathyroidectomy Video-assisted parathyroidectomy Videoscopic parathyroidectomy Equally high cure rate Advantages Reduce operative time allow operation under LA reduce morbidity (transient hypocalcemia / recurrent laryngeal nerve injury) reduce hospital costs, shorten hospital stay Key to success lie in preop localization of pathology gland, identify patient suitable for MIS

Minimally Invasive parathyroidectomy Pre-operative Intra-operative Ultrasound Sestamibi scan CT MRI Angiography / selective venous sampling PTH assay Ultrasound Gamma probe who to operate, where to operate and when to stop operate Pre-op localization – to look for candidate for MIP, and direct surgical exploration to most likely location Intra-op – USG / gamma probe – to help locate pathology; PTH to determine cure USG and mibi – commonly used pre-op imaging CT / MRI less commonly used for pre-op localization, more commonly used in failed parathyroidectomy to detected ? Ectopic (often mediastinal gland) or when finding of USG and MIBI discordant

Ultrasound Sensitivity (55-83%) High frequency linear transducer Ruda et al, Otolaryngol Head Neck Surg 2005; 132:359–372 High frequency linear transducer Carotid arteries – hyoid bone – sternal notch Parathyroid adenoma Gray-scale image Oval / bean-shaped Homogenously hypoechoic Doppler Characteristic arc / rim of vascularity Present in 83% Lane MJ, Am J Roentgenol. Sept 1998; 171(3:819-23) (12-15MHx), some write 8-13MHx Allow anatomical detection of enlarged parathyroid Posterior to thyroid gland, frequently medial to common carotid artery Larger ones can be multilobulated Normal parathyroid glands not commonly seen – 5mmx3mmx1mm vs adenoma have 10x their size; normal glands 50% fat content, isodense as thyroid vs adenoma hypercellular and appear hypoechoic characteristic extrathyroidal feeding vessel (typically a branch off the inferior thyroidal artery), which branch around the periphery of gland before penetrating deeper, resulting in a characteristic arc or rim of vascularity; (imaging) internal vascularity commonly seen in peripheral distribution; Lan et al noted in 83% of his patient (Lane MJ, Am J Roentgenol. Sept 1998; 171(3:819-23)

USG by surgeon Sensitivity of USG Sensitivity of USG + MIBI – 98% Specific side – 84% Specific quadrant – 79% Sensitivity of USG + MIBI – 98% 43 cases, unilat 23, bilat in 20 (11 due to lack of IOPTH, 7 due to localization to opp side, 2 previous neck incision) Drawback – MIBI % sensitivity, lower then quoted in literature

Sestamibi scan Istopic scan with technetium Tc 99m sestamibi Single isotope dual phase scan IV injection  early and delayed image Correlate with larger size / predominance of oxyphil cells / presence of P-glycoprotein Bhatnagar et al, J Nucl Med 1998;39:1617-1620 Carpentier et al, J Nucl Med 1998;39:1441-1444 Tc 99m sestamibi taken up by (mitochondria rich cells) both thyroid and parthyroid glands, abnormal (adenoma / hyperplastic) parathyroid tissue shows increased uptake and retain tadiotracer longer IV injection of radiogtracer, early and delayed image are acquired; early phase obtained 10-15min after injection, called thyroid phase as Tc 99m sestamibi rapidly concentrated in thyroid gland; delayed phased obtained 1.5-3 hour after injection, called parathyroid phase, which emphasize the differential washout of Tc99m sestamibi from abnormal parathyroid glands MIBI uptake correlate with size of gland and cytological compoition (greater uptake in adenoma with predominance of oxyphil cells c/t chief cells)

Advantage Sensitivity (68-95%) Good at identifying ectopic glands in mediastinum or deep cervical location Sensitivity (68-95%) Ruda et al, Otolaryngol Head Neck Surg 2005; 132:359–372 Solitary adenoma 88% Hyperplasia 44% Double adenoma 30% Sensitivity-SPECT Solitary adenoma 90% Hyperplasia 4% Double adenoma 73% Civelek et al. surgery 2002; 131:149-157

Planar imaging SPECT/CT SPECT

Planar, SPECT or SPECT/CT Dual SPECT/CT = early SPECT/CT + SPECT / Planar > any dual Dual SPECT = dual planar use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. 2009 EANM parathyroid guidelines. Dual phase SPECT/CT > dual phase SPECT / planar Early phase SPECT/CT + any form of delayed imaging > dual phase SPECT / planar

USG vs MIBI Sensitivity of USG – 65% Sensitivity of MIBI-SPECT – 68% Detected only by one modality – 16%  USG and MIBI complementary 31 cases with both pre-op imaging; USG + dual planar + delay SPECT OT done, retrospective evaluation of imaging modalities Sensitive = able to pick up adenoma Sensitivity of USG + MIBI – 74%

USG + MIBI Sensitive = identify adnoma about region Accuracy = localize adenoma to supreior / inferior gland All adenomas are correctly localized, superior glands incorrectly locaized t inferior glands, as superior glands tebd to prolapse inferiorly as they enlarge No sign diff in

USG + MIBI Surgical failure w/o PTH – 2% With PTH – 1% P=0.5 Sensitive = identify a positive site of adenoma Concordant MIBI + USG  focused surgery + PTH  bilateral; 322 concordant; 319 localize and remove adenoma while 3/322 fail PTH drop and find additional disease; 3/319 failed correct hyperclacemia Discordant MIBI + USG  focused surgery with MIBI result + PTH  bilateral; 201 discordant 125 (62%) correct localization Planar view Studies showed that accuracy improved when both imaging studies done pre-operatively Scheiner et al Clin radiology 2001; 56:984-988 Purcell etal; Arch Surg 1999;134:824-830 DeFeo et al; Radiology 2000; 214:393-402

Reoperation?

163 patients with ?missed adenoma Pre-op localization  surgery 6 –ve exploration, all persistent hypercalcemic 2 patient with +ve exploration suffered persistent hypercalcemia, suggest multigland disease Another 2 Recurrent HPT in FU 163 patients with ?missed adenoma Pre-op localization  surgery 140 unilateral exploration 18 mediastinal procedure 92% long term resolution of hypercalcemia

Sensitivity = 70% IV – discordant USG and MIBI, 13/14 false +ve given by USG When USG +Ve, MIBI –ve, successful in 97%, majority in neck III – 92 patient with at least 1 invasive MIBI highest PPV in non-invasive FNA greatest PPV in invasive, but small numble applicable only Arteriogram vs + stimulated venous sampling – similar 70 out of 71 patient operate base on non-invasive imaging along cured

Proposed strategy Diagnosis, exclude other causes of hypercalcemia Operative reports Pathology slides Indication of surgery Suggest CT over MRI if MIBI identify adenoma in mediastinum, as CT greater PPV

? False positive 17 patient post parathyroidectomy persistent hypercalcemia and “false +ve” pre-op MIBI scan repeated MIBI +ve for all case, showing the same foci as pre-op scan, eventually adenoma identified with radioguided surgery Assumed false +ve as surgeon failed to identified adenoma All repeated scan showed same foci of radioactivity  Errors in interpertation rather than in scan itself

John Doppman 1986 “The best localization study prior to primary exploration in a patient with primary hyperparathyroidism is to locate an experienced parathyroid surgeon”

Initial surgery: MIBI + USG if MIP Both +ve Concordant result MIP (? IOPTH) Discordant result  IOPTH mandatory if MIP One +ve  IOPTH mandatory if MIP Both -ve  bilateral exploration Re-operation MIBI as first line USG / CT / MRI FNA / arteriogram / SVS An experienced surgeon is the key to success

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