Routine vs Selective Calcium Supplementation After Total Thyroidectomy

Importance: Postoperative hypocalcemia is the most frequent complication after total thyroidectomy. Prophylactic supplementation with calcium and calcitriol (C+C) is widely used, but selective administration based on early postoperative parathyroid hormone (PTH) levels may reduce overtreatment. Objective: To compare the incidence of symptomatic and biochemical hypocalcemia with routine prophylactic C+C and selective supplementation guided by postoperative PTH levels. Design, Settings, and Participants: This was a multicenter, pragmatic, randomized clinical trial conducted from June 1, 2022, to July 31, 2024, at 3 tertiary hospitals with adult patients undergoing total thyroidectomy for benign or malignant disease. Exclusion criteria included prior parathyroid surgery and calcium metabolism disorders. Data were analyzed from October 1, 2024, to March 30, 2025. Interventions: Selective supplementation when 4-hour postoperative PTH level was less than 15 pg/mL (PTH group; to convert to ng/L, multiply by 1) or routine prophylactic C+C for 15 days (C+C group). Main Outcomes and Measures: Symptomatic hypocalcemia at 15 days postoperatively, assessed via a symptom scale. Secondary outcomes included biochemical hypocalcemia adverse events, calcium supplementation, and readmissions. Results: The analysis included a total of 258 participants; the PTH group comprised 117 patients (mean [SD] age, 50.3 [15.2] years; 100 women [85.5%]) and the C+C group, 141 patients (mean [SD] age, 49.8 [15.9] years; 118 women [83.7%]). Bethesda III to VI nodules were present in 57 (48.7%) and 62 patients (44.0%), respectively. Symptomatic hypocalcemia occurred in 24 patients overall (9.3%), 11 (7.8%) in PTH group and 13 (11.1%) in C+C group (odds ratio [OR], 0.68; 95% CI, 0.29-1.57; P = .36). In the subgroup with complete biochemical data, biochemical hypocalcemia was observed in 29 of 148 participants (16 in PTH [21.6%] and 13 in C+C [17.6%]) (OR, 1.29; 95% CI, 0.57-2.93; P = .53). Adverse events and complications were similar across groups. The PTH group needed less calcium supplementation. Conclusions and Relevance: This randomized clinical trial found that selective calcium supplementation based on postoperative PTH values was not superior to routine calcium supplementation for preventing symptomatic or biochemical hypocalcemia after total thyroidectomy. Either strategy may be used, with choice depending on resource availability and clinical setting. Trial Registration: ClinicalTrials.gov Identifier: NCT05252884.