1. Evolution of Parathyroid Surgery Using Sestamibi Imaging Guidance David R. Byrd, MD Department of Surgery University of Washington

2. Disorders of Parathyroid Glands hypoparathyroidism -rare. Almost always caused by excessive surgical removal of parathyroid tissue (iatrogenic) during thyroid or parathyroid surgery hyperparathyroidism (HPT): –primary - hi Ca++, hi PTH - usually due to single adenoma (90%), cured by removal of adenoma –secondary - lo Ca++, hi PTH, seen in chronic renal failure - not a surgical problem –tertiary - hi Ca++, hi PTH, seen after renal transplant - hyperplasia of all 4 glands

3. Traditional Surgery for Hyperparathyroidism primary HPT - 4 gland exploration, remove adenoma, biopsy 3+ normal glands tertiary HPT (after renal transplantation) - 3 1/2 gland removal +/- forearm autotransplant

7. Complications of Parathyroid Surgery persistent HPT - 1-20% (experience dependent) temporary or permanent hypocalcemia - 1- 20% nerve injury - recurrent or superior laryngeal - 1-10% bleeding - <5%

8. Unilateral Exploration for Primary HPT if: one abnormal, hypercellular gland and one normal gland found on one side, no contralateral exploration occasional use of preop thallium-technetium scan results of 5 studies - cure 93-100%

9. Indications for Operation in Asymptomatic Patient w/ Primary HPT - NIH Consensus(1990) markedly elevated serum Ca++ episode of life-threatening hyperCa++ reduced creatinine clearance renal stones markedly elevated 24 hr urinary Ca++ substantially reduced bone mass (by DEXA scan) age <50 (relative indication for surgery)

10. Parathyroid Imaging Tc-99m sestamibi scan (Cardiolyte) ultrasound initially thought useful only in persistent or recurrent disease thallium-technetium subtraction scan - now rarely used

11. Tc-99m Sestamibi Scan taken up by actively metabolizing tissues - salivary glands, thyroid, parathyroid glands over time, blood flow causes washout from thyroid and normal parathyroid glands delayed images show a discrete “hot spot” in 75-80% patients with primary HPT can be used to direct minimally invasive surgical approaches

12. Parathyroid Imaging - Tc-99m Sestamibi 45 min Anterior45 min LAO 2 HR submandibular gland thyroid lobe adenoma Delayed views

13. Right inferior pole parathyroid adenoma 15 min Ant1 hr Ant1 hr RAO adenoma

14. 15 min Ant1 hr Ant Right superior parathyroid adenoma adenoma

15. Advances Enabling Localized Exploration Tc-99m sestamibi radioguided exploration rapid IOPTH assay - 1/2 life = 3-5 minutes

16. Rapid IOPTH Assay exploits short half life (3-5 minutes) of PTH serum baseline level #1 prior to exploration level #2 after exploration but before removal adenoma levels 5 & 10 minutes after adenoma removal 5 minute level > 50% second baseline level = high prediction of success -Irvin G, et al, 1993

17. Studies of IOPTH Measurement in HPT solitary/Uni/bilat.Cure rate # pts MGDexploration ( %) Nussbaum 19881212/08/4100 Chapuis 1996173 --160/13 94 Irvin 1993 61 -- -- 90 Sofferman 1998 4031/9 --100 Carty 1997 6758/942/25 99 Irvin 1994 1818/0 -- 89 Starr 2001 5038/12 0/50 92

18. Minimally Invasive Radioguided Parathyroidectomy (MIRP) only in patients who localize by pre-op sestamibi scan (75% with primary HPT) sestamibi scan performed 2-3 hours before exploration - timing crucial gamma probe used to find the “hottest” spot ex vivo adenoma counts >20% background no further dissection and no frozen section if no adenoma found, 4 gland exploration -Norman J, et al, 1997

23. MIRP - results 2 cm incision local w/ sedation, out-patient procedure 100% cure rate no complications mean operating time = 25 minutes re-operative cure rate = 100% -Norman J, 1997

24. Studies of MIRP in HPT solitary/Uni/bilat.Cure rate # pts MGDexploration ( %) Martinez 32/1 -- -- Gallowitsch12 -- -- -- Bonjer 6249/10 -- 95 Norman 1515/0 14/1 -- Norman 2421/0 21/1 -- Flynn 3932/6 30/9 100

25. Evolution of Surgery for Primary HPT Preoperative sestamibi in all patients with primary HPT: –help decision whether to operate in selected patients –localize adenoma to plan localized exploration Minimally invasive parathyroidectomy (MIP): –2-4 cm incision –often w/ local + sedation –out-patient procedure –+/- IOPTH testing - biochemical confirmation Endoscopic removal of parathyroid gland(s)

26. Right inferior parathyroid adenoma - 54F 15 min Ant1 hr Ant1 hr RAO adenoma

27. IOPTH Testing and Results Baseline #1214 Baseline #2157 5 minute post32 10 minutes post20 MIP findings - 500mg L inferior pole adenoma F/U levels 3 mos: Ca++ = 9.5, PTH = 55 (both normal)

28. Case # 3 50M, asymptomatic: - serum Ca++ = 13.4 - preop iPTH = 750 - concern for carcinoma

29. Tc-99m sestamibi positive for intense uptake LIP Immed Ant Delay Ant

31. IOPTH Testing and Results Baseline #11259 Baseline #2764 5 minute post129 10 minutes post93 Case #3: 50M, 4.2 LIP gm adenoma Early F/U: Ca++ =8.8, PTH = 138 (low calcium, sl. elevated PTH)

32. Operation for Tertiary HPT standard operation remains 3 1/2 gland removal or total parathyroidectomy w/ auto transplant dorsal forearm Imaging not standard at present selected patients may benefit from Tc-99m sestamibi preop scan role of IOPTH testing evolving