Does Preoperative Calcium and Calcitriol Decrease Rates of Post-Thyroidectomy Hypocalcemia? A Randomized Clinical Trial

Abstract

BACKGROUND: Postoperative hypocalcemia is the most common complication after thyroidectomy. Postoperative supplementation with calcium and calcitriol reduces its occurrence; however, prophylactic preoperative supplementation has not been studied systematically. The primary objective of this study was to determine whether pre- and postoperative calcium and calcitriol supplementation reduces postoperative hypocalcemia after total thyroidectomy compared with postoperative supplementation alone. STUDY DESIGN: We conducted a single-institution prospective randomized trial enrolling 82 patients undergoing total thyroidectomy from July 2017 through May 2019. Those undergoing partial thyroidectomy or concurrent planned parathyroidectomy were excluded. The intervention group started calcitriol 0.25 μg po bid and calcium carbonate 1,500 mg po tid 5 days preoperatively and continued postoperatively. The control group started these medications postoperatively. The primary end point was clinical or biochemical hypocalcemia. Secondary outcomes were postoperative calcium levels, need for intervention, length of stay, and readmission. RESULTS: Thirty-eight patients were randomized to the intervention group and 44 to the control group. There were 12 episodes of hypocalcemia; 5 (13.2%) in the intervention and 7 (15.9%) in the control group (p = 0.76). No differences were found in secondary outcomes; including postoperative calcium levels at each measured time point, need for intervention (n = 10 [26.3%], n = 15 [34.1%]; p = 0.48), length of stay (mean [SD] 32.3 [15.6] hours, 30.7 [10.5] hours; p = 0.6), or readmissions (n = 0 [0.0%], n = 3 [6.8%]; p = 0.24). CONCLUSIONS: Starting supplementation with calcium and calcitriol preoperatively does not reduce postoperative hypocalcemia compared with postoperative supplementation alone after total thyroidectomy. These findings do not support the practice of routine calcium and calcitriol supplementation before total thyroidectomy.

Preoperative supplementation of calcitriol and calcium relieves symptom and extent of hypocalcemia in patients undergoing total thyroidectomy and bilateral central compartment neck dissection: A prospective, randomized, open-label, parallel-controlled clinical study

“…Interestingly, just before releasing our results, two newly emerged published studies have demonstrated various and even opposite results (17,18). The key reason for the opposite conclusion lies in analyzing the calcium levels based on further subgrouping postoperative PTH levels.…”

“…In our study, all 172 patients received bilateral central compartment neck dissection. In contrast, only 11.0% [9 out of 82, reported by Donahue et al (17)] patients and 27.7% [13 out of 47, reported by Shonka et al ( 18)] underwent central compartment neck dissection. In this setting, patients in our study had higher rates of transient hypoparathyroidism and symptomatic hypocalcemia.…”

“…Conversely, patients without transient hypoparathyroidism exhibited comparable calcium fluctuation, which further strengthened the fact that the calcium level was also comparable in patients without transient hypoparathyroidism among the three The discrepancy in the conclusion among studies is interesting and raises questions about the need for a preoperative protocol. Notably, the three clinical trials exhibited distinct differences in patient selection (17,18), especially in the surgical procedure the patients underwent. In most studies from Western countries, the reported total thyroidectomy included various diagnoses besides thyroid cancer (3,(17)(18)(19): retrosternal or multinodular goiter and Grave's disease, indicating the function of the lower pole parathyroid gland that might be better preserved.…”

“…Notably, the three clinical trials exhibited distinct differences in patient selection (17,18), especially in the surgical procedure the patients underwent. In most studies from Western countries, the reported total thyroidectomy included various diagnoses besides thyroid cancer (3,(17)(18)(19): retrosternal or multinodular goiter and Grave's disease, indicating the function of the lower pole parathyroid gland that might be better preserved. Furthermore, even for thyroid cancer surgery, whether to perform prophylactic central compartment neck dissection is controversial and diverged among different areas.…”

Post-thyroidectomy hypocalcemia and related complications

“…The incidence of symptomatic hypocalcemia in patients with Basedow-Graves disease (GD) was 50.0% for those clinically treated and 43.0% for those not treated, with no statistical difference between them (Bugălă et al, 2022;Palmhag et al, 2021;Şahbaz et al, 2018;Soylu & Teksoz, 2020;THAKUR, 2021). In contrast, Donahue et al, (2021) did not consider hyperthyroidism as a predictive factor for postoperative hypocalcemia, but empirically treated all patients postoperatively with calcium carbonate and/or vitamin D (Donahue, Pantel, Yarlagadda, & Brams, 2021). Phookan et al, (2021), Moran et al, (2020) and Wojtczak et al, (2018) commented that toxic goiter, as it is more vascularized, contributes to increased perioperative bleeding, reducing the visibility of the surgical field (Moran et al, 2020;Phookan et al, 2021;Wojtczak, Aporowicz, Kaliszewski, & Bolanowski, 2018).…”