1. Surgical Management of Renal Hyperparathyroidism MY Chan Queen Mary Hospital

2. Background Renal hyperparathyroidism (Renal HPT) Secondary: overproduction of parathyroid hormone (PTH) in response to hypocalcaemia Tertiary: excessive secretion of PTH after longstanding secondary hyperparathyroidism Epidemiology 11-15 per 1000 patient-years 1 1–2% of patients with secondary HPT require parathyroidectomy each year 2 1.Slinin Y, Foley RN, Collins AJ. Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study. Hemodialysis international. International Symposium on Home Hemodialysis [Internet]. 2007 Jan;11(1):62–71. 2.Triponez F, Clark O, Vanrenthergem Y, et al. Surgical treatment of persistent hyperparathyroidism after renal transplantation. Ann Surg 2008;248:18.

4. Indications Not well established No studies to define biochemical criteria K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease 1 Severe hyperparathyroidism (>88 pmol/L) with hypercalcaemia and/or hyperphosphataemia resistant to medical therapy Calciphylaxis with documented elevated PTH 1.National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease.Am J Kidney Dis 42:S1-S202; 2003 (suppl 3)

5. Pre-operative Imaging To locate any ectopic or supernumerary gland(s) Technetium Tc-99m sestamibi (MIBI) scintigraphy Sensitivity of 44-82% in published works 1 Ultrasound scan Sensitivity of 24-54% in published studies 1 Limited reports on CT and MRI Not a must before operation Limited value because of the poor results in identifying all the glands in multi-gland disease 1.Lai ECH, Ching ASC, Leong HT. Secondary and tertiary hyperparathyroidism: role of preoperative localization. ANZ journal of surgery [Internet]. 2007 Oct [cited 2013 Jan 27];77(10):880–2.

6. Operative Strategies Subtotal parathyroidectomy (SPTX) Resection of 3 ½ parathyroid gland The most healthy looking parathyroid gland chosen Leaving a portion of viable parathyroid gland and marked with clip Total parathyroidectomy with autotransplantation (TPTX+AT) The most healthy looking parathyroid gland chosen Implantation of a portion of parathyroid gland Total parathyroidectomy without autotransplantation (TPTX)

7. Operative Strategies Takagi et al (1984) 1 20 of 43 patients underwent SPTX 23 underwent TPTX+AT 40% in SPTX group required IV calcium supplement 91% in TPTX+AT group Mean duration of administration 15.6 days in SPTX group 59.5 days in TPTX+AT group 1.Takagi H, Tominaga Y, Uchida K, Yamada N, Kawai M, Kano T, et al. Subtotal versus total parathyroidectomy with forearm autograft for secondary hyperparathyroidism in chronic renal failure. Annals of surgery [Internet]. 1984 Jul;200(1):18–23.

8. Operative Strategies Retrospective study by Lorenz et al. (2006) 1 23 patients underwent TPTX 64 patients underwent SPTX Normalization of PTH 74% in TPTX group 63% in SPTX group Symptomatic hypocalcaemia requiring intravenous supplement 2 patients (8.7%) in TPTX group 0 patients in SPTX group No comparison of long-term results between 2 groups 1.Lorenz K, Ukkat J, Sekulla C, Gimm O, Brauckhoff M, Dralle H. Total parathyroidectomy without autotransplantation for renal hyperparathyroidism: experience with a qPTH-controlled protocol. World journal of surgery [Internet]. 2006 May [cited 2013 Jan 15];30(5):743–51.

9. Operative Strategies Retrospective study by Schneider et al (2012) 1 606 patients with mean follow-up of 57.6 months No significant difference in terms of perioperative drop in calcium / PTH and rate of nerve palsy Persistent disease requiring reoperation 4.8% in SPTX group 0.4% in TPTX+AT group 0% in TPTX group Recurrent disease requiring reoperation 9.5% in SPTX group 5.4% in TPTX+AT group 0% in TPTX group 1.Schneider R, Slater EP, Karakas E, Bartsch DK, Schlosser K. Initial parathyroid surgery in 606 patients with renal hyperparathyroidism. World journal of surgery [Internet]. 2012 Feb [cited 2013 Jan 19];36(2):318–26.

10. Operative Strategies ProsCons SPTX Lesser requirement of post-operative calcium supplement Higher rate of persistent / recurrent disease Difficulty in reoperation TPTX+AT Allow easy access / differentiation in recurrence Decreased rate of recurrence Larger requirement of calcium supplements than SPTX immediately post-op TPTX Low rate of recurrence Possibly higher chance of adynamic bone disease Cryopreservation required

11. Operative Strategies Cervical thymectomy Retrospective study by Schneider et al. (2011) 461 patients underwent parathyroidectomy with routine bilateral cervical thymectomy 44.5% of patients had intrathymic parathyroid gland Ectopic gland in 38% Supernumerary gland in 5.2% Should be carried out if not all 4 glands found 1.Madorin C, Owen RP, Fraser WD, Pellitteri PK, Radbill B, Rinaldo A, et al. The surgical management of renal hyperparathyroidism. European archives of oto-rhino-laryngology: official journal of the European Federation of Oto- Rhino-Laryngological Societies (EUFOS): affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery [Internet]. 2012 Jun [cited 2013 Jan 19];269(6):1565–76.

12. Outcomes Complications Hypocalcaemia 1 (Hungry bone syndrome) High risk group: long-standing HPT, increased ALP, extensive bone resorption on X-ray Recurrent laryngeal nerve palsy (<1% with permanent injury) Bleeding and haematoma, wound infection Increased short-term mortality (3.1 vs. 1.2% 30-day mortality) 2 Decreased long-term mortality (median survival 53 vs. 47 months) 2 Other benefits: improved bone density, pruritis and calciphylaxis 1.Schlosser K, Zielke a, Rothmund M. Medical and surgical treatment for secondary and tertiary hyperparathyroidism. Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society [Internet]. 2004 Jan;93(4):288–97 2.Madorin C, Owen RP, Fraser WD, Pellitteri PK, Radbill B, Rinaldo A, et al. The surgical management of renal hyperparathyroidism. European archives of oto- rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS): affiliated with the German Society for Oto-Rhino- Laryngology - Head and Neck Surgery [Internet]. 2012 Jun [cited 2013 Jan 19];269(6):1565–76..

13. Conclusions Parathyroidectomy is an effective treatment of renal hyperparathyroidism Pre-operative imaging may help but is not necessary Thorough exploration aiming to identify all 4 glands is essential no matter which type of operation is chosen No evidence to show any type of operation is superior than the others

14. Thank You

15. Calcimimetics Enhances sensitivity of calcium-sensing receptors Lowers PTH, serum calcium and phosphate levels Multicenter, prospective, randomized, placebo- controlled trial published in 2012 (EVOLVE trial) 1 3883 patients with secondary HPT included In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis 1.Chertow, G. M., Block, G. a, Correa-Rotter, R., Drüeke, T. B., Floege, J., Goodman, W. G., Herzog, C. a, et al. (2012). Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. The New England journal of medicine, 367(26), 2482–94.