1. Dr Guy ANDRY, M. MOREAU, I.EL MOUSSAOUI, E. WILLEMSE, M. QUIRINY, A. DIGONNET Université Libre de Bruxelles, Brussels

2. Despite all the methods to evaluate and to predict postoperative hypocalcemia, no consensus exists on the role of routine calcium and/or Vit. D following thyroid surgery MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA

3. Hypocalcemia is the most frequent complication after total thyroidectomy Transient: 9 to 50 % Permanent: 0.5 to 13% (→ 33 %)

4. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Patients and methods Patients were prospectively registered from January 2006 till December 2009. Calcemia (phosphoremia) pre and postop Pth levels After the first blood sample (2 to 3 hours postop.): calcium gluconate 2 g/l of perfusion if calcemia ≤ 8.2 mg/dl Symptoms and signs of hypocalcemia registered

5. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Patients and methods From postop day 1 to day 2 (discharged): pth, calcemia, phosphoremia  Treatment for Ca < 8.0 mg/dl for 8.0 < Ca < 8.3 mg/dl - 1 g calcium carbonate TID - 1g calcium BID - Alfacalcidiol 1 mcg/day - Alfacalcidiol 1 mcg/day  0.5 mcg/day Day 6 to 10 (outpatient clinic): pth, calcemia, phosphoremia and OH-vitD, TSH; T4L, …

6. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Materials & methods Pth level and calcemia : between 5th and 10th day postop, after 1 month, 3 months, 6 to 9 months, 1 year; 1/yr thereafter if prolonged hypocalcemia

7. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Results (1) (near) total thyroïdectomy (or totalisation): 537 pts from Jan 2006 till Dec 2009 (421:W; 116:M) Mean age: 51 yrs (12-82) Selective neck dissection (mainly central compartment: 63 pts) Cancer: 81 pts (72 PTC, 5 MTC, 4 follicular) Multinodular goiter: 415 (50 with throiditis) Basedow : 29 12 pts (benigh adenomas, follicular nodule, …)

8. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Results (2) 43.4% (n=233) developped a transient hypocalcema 3.91% (n=21) developped a 1 year hypocalcemia 3.17% (n=17) prolonged hypocalcemia 4 PTS had a PTH normal level 15, 23, 32, 39 pg/ml but maintained calcemic supplements to avoid symptoms

9. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Results (4) PTS characteristics for prolonged hypocalcemia No (n=520)Yes (n=17)Pvalue Malignant14.6%43.8% Parathyroid I&P* 1.2 3 4 1.9% 6.5% 91.6% 11.8% 17.6% 70.6% Lymph node dissection 11.2%29.4% Weight of specimen 47.5 (SD  49.5) 55.4 (SD  55.1) 0.51 Hosp stay (d) 4.08 (SD  0.79) 4.2 (SD  0.84) 0.79 * Identified and Preserved 0.001 0.022 0.004

10. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Results (6) Sensibility, specificity, ODDS ratio of hypocalcemia hypoPTH to predict « definitive » hypocalcemia Ca: calcemia; PTH: level of « intact » on ice; 4 hrs: 4 hours postop; J1 to x: J postop 1 to x SensitivitySpecificityODD1 ratio Pvalue Ca 4 hrs < 8 mg/dl Ca J1 < 8 mg/dl Ca J5-20 < 8 mg/dl Ca J30 < 8 mg/dl 17.65% 70.60% 92.30% 31.30% 90.3% 64.7% 94.3% 98.3% 2 4.4 196.1 25.6 0.28 0.0029 < 0.0001 PTH 4 hrs < 15 pg/ml PTH J1 < 15 pg/ml PTH J5-20 < 15 pg/ml PTH J30 < 15 pg/ml 100% 90% 63.6% 62.4% 56.4% 68.5% 92.2% ∞ 19.6 20.7 <.0001

11. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Discussion (1) Hypocalcemia postop J5-20: < 8 mg/dl (sens: 92.3%; specif : 94.3%) Hypo PTH level postop < 15 pg/ml are predictive of definitive hypocalcemia ROC curve was constructed  PTH early < 9 pg/ml is predictive of definitive hypocalcemia: 100% sensitivity 76% specificityODDS ratio ∞ p < 0.0001

12. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Discussion (2) Late recovery of normal parathormone activity Among 21 PTS with prolonged hypocalcemia 4 showed normal calcemia and PTH levels after 4, 5, 6 and 7 yrs (4 parathyroids respected during the operation; 2 M, 2W; 3 MN Goiters, 1 Basedow)

13. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA Role of postoperative vitamin D and/or calcium routine supplementation in preventing hypocalcemia after thyroidectomy: a systematic review and meta-analysis A. Alhefdhi et al, The Oncologist 2013;18:539-542

14. Role of postoperative vitamin D and/or calcium routine supplementation in preventing hypocalcemia after thyroidectomy: a systematic review and meta-analysis (1) Out of 1180 studies on hypocalcemia post T thyroidectomy 9 studies responding to the strength of recommendation taxonomy grading system (SORT)* * Ebell M.H. 2004, J. Am. Board Fam. Pract. N = 2285 PTS Symptomatic hypocalcemia (%) 22 PTS : vit D only 580 PTS : Ca ++ only 792 PTS : vit D + Ca ++ 891 PTS : no 4.6 % 14 % 20.5 % After A. ALHEFHI & al 2013

15. Conclusion Systematic assays of iPTH at 4 hrs Ca ++ between D5-20 are a good indicators of prolonged, hypoparathyroidism hypocalcemia. Immediate postop administration of IV Ca ++ gluconate (2 g/l) followed at D 1-2 by calcidial 1 mg and calcium carbonate (1 to 6 g tailorized by Ca ++ levels) prevent the stress of symptomatic hypocalcemic. MANAGEMENT OF POSTOPERATIVE HYPOCALCEMIA