1. Dr Annie NK Chiu United Christian Hospital Joint Hospital Surgical Grand Round 20 th Apr 2013

2. Introduction Thyroid surgery is a common operation 1751 thyroid operations in 2011/12 in HA hospitals Postoperative hypocalcemia is one of the most common complications after total or completion thyroidectomy Temporary: 1.6% - 50% Permanent (> 6 months): 0.5% - 2% 1.Surgical outcomes monitoring & improvement program (SOMIP) report. Vol 4 Jul 2011-Jun 2012 2.Reeve T, Thompson NW. Complications of thyroid surgery: how to avoid them, how to manage them, and obsevations on their possible effect on the whole patient. World J Surg. 2000; 24(8): 971-975

3. Post-thyroidectomy Hypocalcemia Multifactorial Hypoparathyroidism – most important cause Stunning Devascularization Inadvertent resection

4. Post-thyroidectomy Hypocalcemia Increased risk of postoperative hypocalcemia Malignant disease Central neck dissection Documented resection of parathyroid gland at operation (with or without autotransplantation) Landry CS et al. Predictable criteria for selective, rather than routine, calcium supplementation following thyroidectomy. Arch Surg 2012; 147(4): 338-344

5. Management Monitoring clinical symptoms and signs of hypocalcemia Daily monitoring serum calcium level Manifestation 24 – 48 hours after operation, may be delayed up to several days Prolonged hospitalization

6. Does routine calcium supplement prevent post- thyroidectomy hypocalcemia?

7. Routine Supplements after Thyroidectomy There are 2 small RCTs Oral calcium +/- vitamin D supplements Significantly fewer patients developed hypocalcemia Milder symptoms of hypocalcemia Allows earlier discharge 1.Bellantone R et al. Is routine supplementation therapy (calcium and vitamin D) useful after total thyroidectomy? Surgery 132: 1109-1112; discussion 1112-1103 2.Roh JL et al. Routine oral calcium and vitamin D supplements for the prevention of hypocalcemia after total thyroidectomy. Am J Surg 192: 675-678

8. Pitfalls Over treat Multiple doses per day Serial laboratory tests for monitoring Adverse effects of unnecessary calcium supplement: Nausea, decreased appetite, constipation Hypercalcemia – suppress parathyroid function

10. Parathyroid Hormone (PTH) Hypoparathyroidism – most important cause for post- thyroidectomy hypocalcemia PTH half-life: 2-5 minutes Hypothesis – perioperative PTH level predicts post- thyroidectomy hypocalcemia

12. Questions to be answered How accurate When to measure What cutoff value How to apply

13. Early prediction of postthyroidectomy hypocalcemia by one single iPTH measurement. Lombardi CP et al. Surgery 2004; 136: 1236-1241 Prospective study 53 patients underwent total or completion thyroidectomy iPTH < 10 pg/mL (normal range 10-65 pg/mL) at 4 and 6 hours postop correctly predicted hypocalcemia Sensitivity 94%, specificity 100%, overall accuracy 98%

14. Parathyroid hormone early percent change: an individualized approach to predict postthyroidectomy hypocalcemia Chapman DB et al. Am J Otolaryngol 2012; 33: 216-220 Retrospective study 52 patients underwent total or completion thyroidectomy >44% decrease in PTH level at 6-hour postop → Likely to develop hypocalcemia, sensitivity 100% Likewise, if <44% decrease in PTH level at 6-hour, patients can be considered safe for early discharge

16. Meta-analysis of 4 published Australian studies 458 patients Stratified into 2 groups: normal PTH vs low PTH groups Normal postop PTH at 4 hours as a predictor for normocalcemia Sensitivity:92.6% Specificity 70.7% PPV 92.3% 7% of patients with normal postop PTH developed hypocalcemia with mild and self-limiting symptoms Australian Endocrine Surgeons (2007) Guidelines AES 06/01. Postoperative parathyroid hormone measurement and early discharge after total thyroidectomy: analysis of Australian data and management recommendations. ANZ J Surg 77: 199-202

17. Evidence for the Role of Perioperative PTH Measurement after Total Thyroidectomy as a Predictor of Hypocalcemia Grodski S et al. World J Surg 2008; 32: 1367-1373 Systemic review, a Medline search of English language literature Issues addressed: Accuracy of PTH in predicting hypocalcemia Optimal timing for measuring PTH

18. Accuracy of PTH 24 case series, 3 case-control trials Major differences in study designs and data Some studies excluded patients with Graves’ disease or thyroid cancer with central neck dissection Strong correlation of postop PTH with hypocalcemia after thyroidectomy Grodski S et al. Evidence for the role of perioperative PTH measurement after total thyroidectomy as a predictor of hypocalcemia. World J Surg 2008; 32: 1367-1373

19. Accuracy of PTH Recommendations (Grade C): Post-thyroidectomy PTH levels accurately predict hypocalcemia but lack 100% accuracy Both absolute levels and percentage decline showed similar accuracy Progressive and severe hypocalcemia is unlikely if normal postop PTH Facilitates early supplementation therapy Facilitates early and safe discharge Grodski S et al. Evidence for the role of perioperative PTH measurement after total thyroidectomy as a predictor of hypocalcemia. World J Surg 2008; 32: 1367-1373

20. Timing of PTH Sample 4 case series 10 minutes to 24 hours postop Half-life of PTH: 2 – 5 minutes No difference in PTH levels at early postoperative period and days after operation Grodski S et al. Evidence for the role of perioperative PTH measurement after total thyroidectomy as a predictor of hypocalcemia. World J Surg 2008; 32: 1367-1373

21. Timing of PTH Sample Recommendation (Grade C): A single PTH measurement taken any time from 10 min postoperative to several hours later will provide equally accurate results for predicting post-thyroidectomy hypocalcemia. Grodski S et al. Evidence for the role of perioperative PTH measurement after total thyroidectomy as a predictor of hypocalcemia. World J Surg 2008; 32: 1367-1373

22. How to apply it into clinical practice?

23. Use of postoperative PTH in patient management after total or completion thyroidectomy

24. Retrospective study Patients underwent total or completion thyroidectomy Exclusion criteria: modified radical neck dissection, parathyroidectomy, chronic renal disease, preop calcium/ vitamin D supplements Jan 2010 to Mar 2013

25. Results 107 patients: 100 total (93.5%); 7 completion (6.5%) Hypocalcemia – adjusted Ca 2+ <2.00 mmol/L at any time point Transient 47.7% (51/107) Persistent 5.6% (6/107)

26. 107 Patients 54 Patients Group 1-traditional Mx Since June 2011 – Use of postop D1 PTH Before 53 Patients Group 2-PTH guided Mx After

27. Results Comparable in age, sex distribution, type of operation, documented resection of parathyroid gland, paratracheal LN dissection and malignant pathology No difference in rate of hypoparathyroidism, rate of hypocalcemia, need for oral calcium and vitamin D supplement 1 patient from PTH guided Mx group re-admitted due to hypocalcemia

28. Results

30. Postoperative hospital stay (Days) p < 0.0001

31. Conclusions Hypocalcemia is a common complication after total or completion thyroidectomy. Traditionally, patients have to stay in hospital for serial monitoring of serum calcium A single PTH measurement at early postoperative period can accurately predict which patients are prone to hypocalcemia and facilitate early supplementation therapy.

32. Conclusions Asymptomatic patients with normal PTH levels can be safely discharged on the first postoperative day. Patients with normal PTH levels may develop mild and self-limiting hypocalcemia. These patients may be discharged safely with calcium supplements and educations on hypocalcemic symptoms