1. Management of Secondary and Tertiary Hyperparathyroidism - Joint Hospital Grandround 20.12.2003 Henry Joeng Department of Surgery United Christian Hospital, HKSAR

2. Overview Pathophysiology Medical treatment Surgical treatment Indication Pre-op localization study Different types of parathyroidectomies Rapid PTH assay Experience in UCH

3. Secondary Hyperparathyroidism Chronic extrinsic overstimulation of otherwise normal parathyroid gland Diffuse hyperplasia of all 4 PTH glands A negative calcium balance is the key stimulus Chronic renal insufficiency is the commonest cause

4. Tertiary hyperparathyroidism Autonomous hypersecretion of PTH in long lasting secondary hyperPTH despite correction of the underlying cause Commonly seen in post-renal transplantion patient with long history of dialysis beforehand

5. Complications of 2 o /3 o HyperPTH Skeletal Progressive bone demineralization Osteitis fibrosa cystitca Bone pain, pathological fracture Soft tissue calcification Involve different organs or tissues Calciphylaxis

6. Complications of 2 o /3 o HyperPTH Pruritus Other Myopathy Peptic ulcer disease Neuropathy Cardiotoxicity

7. Biochemical changes Elevated “intact” PTH  key feature Elevated phosphate Elevated ALP Normal serum calcium level. Elevated in 3 o hyperPTH

8. Radiological changes Plain X ray Subperiosteal bone resorption “Pepper pot” appearance of skull Bone density Progressive decline

9. Medical treatment Oral calcium supplement Oral 1,25 – D3 supplement Oral phosphate binder

10. Surgical treatment 5-10 % patients on long term dialysis need parathyroidectomy Indication When complications of 2 o /3 o hyperPTH arise. E.g. skeletal cx Medical treatments fail Biochemical parameter E.g. [Ca][PO4] product > 70

11. PTX - Optimization Correct biochemical disturbance due to underlying renal disease Hemodialysis before operation Aggressive pre-op calcium replacement

12. Anatomy of parathyroid gland Upper glands position more constant 77% around the intersection of RLN and inferior thyroid artery Lower glands more variable Lower pole of thyroid, thyrothymic ligament 9% in thymus gland Supernumerary gland in up to 8% cases Butterworth. J R Coll Surg Edinburg 1998

13. PTX - Localization Different from 1 o HyperPTH Multi-gland disease Bilateral neck exploration Locate ectopic or supernumerary PTH glands Sestamibi scan, USG

14. Types of parathyroidectomies Subtotal parathyoidectomy Total parathyroidectomy with autotransplantation

15. Subtotal parathyroidectomy Stanbury, 1960 3 ½ PTH glands resected 50 mg of one viable gland left behind Advantage Less post-op hypoparathyroidism Disadvantage Second neck exploration if persistent or recurrent hyperparathyroidism

16. Total parathyroidectomy with autotransplantation Wells, 1975 Remove all 4 PTH glands Autotransplant one PTH gland, usu into brachioradialis muscle 20 pieces of 1 mm size fragment Separate pockets and marked with non- absorbale suture

17. Total parathyroidiectomy with autotransplantation Advantage Easier to differentiate between hyperfunctioning graft or residual gland in neck Easier to remove hyperfunctioning graft Disadvantage Higher risk of post-op hypoparathyroidism

18. Choice of operation Controversy Persistant/ recurrent hyperPTH Symptom improvement HypoPTH/ Hypocalcemia Literature search Database: Medline, EBM review, EMBase Keywords: 2 o / 3 o hyperparathyroidism, parathyroidectomy, compar$

19. Evidence … 1 RCT comparing subtotal PTX vs Total PTX with autotransplantation Rothmund. Word J Surg 1991

20. Rothmund, 1991 SPTXPTX+AT No. of patient20 Persistent hyperPTH4/200/20p<0.03 Symptom improvement Bone pain61%87% Radiological sign of renal osteodystrophy 33%69%p<0.05 Muscle weakness20%83%p<0.04 Pruritus45%100%p<0.005 Hypocalcemia1/20

21. Total parathyroidectomy alone Remove all 4 PTH glands Not widely practiced, due to post-op hypoparathyroidism and risk of adynamic bone disease Recent case series and non-randomized comparative studies  feasible method

22. Role of rapid PTH assay Short ½ life of intact PTH Immunochemiluminometric assay Confirm adequate resection and alert the possibility of supernumerary gland At 10min after resection, decrease iPTH of >60% is predictive of cure Chou. Archives of Surgery. 2002 Mar

23. UCH experience From 5.2002 till 12.2003 15 patients with renal failure and 2 o /3 o hyperPTH Total PTX + AT in all patients Transcervical thymectomy in 4 patients Hemithyroidectomies in 3 patients

24. UCH experience Mean FU 7.7 months (0.5 – 20) Mean Duration of dialysis 7.3 yrs (2 – 17) Persistent/ recurrent hyperPTH 4/15 (26.7%) iPTH > 7.7 pmol/l Asymptomatic No need of re-exploration Improvement in bone pain 7/7 (100%) 2/15 patients had undetectable iPTH

25. Summary 5-10% patients on dialysis need parathyroidectomy due to development of complication Total PTX + autotransplantation and subtotal PTX are the common surgical options Rapid PTH assay may be a useful adjunct