High‐dose preoperative cholecalciferol to prevent post‐thyroidectomy hypocalcaemia: A randomized, double‐blinded placebo‐controlled trial

Abstract

Summary Objective Post‐thyroidectomy hypocalcaemia is a significant cause of morbidity and prolonged hospitalization, usually due to transient parathyroid gland damage, treated with calcium and vitamin D supplementation. We present a randomized, double‐blinded placebo‐controlled trial of preoperative loading with high‐dose cholecalciferol (300 000 IU) to reduce post‐thyroidectomy hypocalcaemia. Patients and Measurements Patients (n = 160) presenting for thyroidectomy at tertiary hospitals were randomized 1:1 to cholecalciferol (300 000 IU) or placebo 7 days prior to thyroidectomy. Ten patients withdrew prior to surgery. The primary outcome was post‐operative hypocalcaemia (corrected calcium <2.1 mmol/L in first 180 days). Results The study included 150 patients undergoing thyroidectomy for Graves’ disease (31%), malignancy (20%) and goitre (49%). Mean pre‐enrolment vitamin D was 72 ± 26 nmol/L. Postoperative hypocalcaemia occurred in 21/72 (29%) assigned to cholecalciferol and 30/78 (38%) participants assigned to placebo (P = 0.23). There were no differences in secondary end‐points between groups. In pre‐specified stratification, baseline vitamin D status did not predict hypocalcaemia, although most individuals were vitamin D replete at baseline. Post‐hoc stratification by day 1 parathyroid hormone (PTH) (<10 pg/mL, low vs ≥10 pg/mL, normal) was explored due to highly divergent rates of hypocalcaemia in these groups. Using a Cox regression model, the hazard ratio for hypocalcaemia in the cholecalciferol group was 0.56 (95%CI 0.32‐0.98, P = 0.04) after stratification for Day 1 PTH. Further clinical benefits were observed in these subgroups. Conclusions Pre‐thyroidectomy treatment with high‐dose cholecalciferol did not reduce the overall rate of hypocalcaemia following thyroidectomy. In subgroups stratified by day 1 PTH status, improved clinical outcomes were noted.

Post-Operative Permanent Hypoparathyroidism and Preoperative Vitamin D Prophylaxis

“…This study also analysed day 1 postoperative PTH levels, which are a useful marker of postoperative hypoparathyroidism. Rowe et al (2019) conducted a subgroup analysis dichotomized by day 1 PTH status (<10 pg/mL, below the lower limit of the local reference range; ≥10 pg/mL, normal); they found more favourable clinical outcomes in the participants of both the low and normal PTH subgroups who had received preoperative cholecalciferol (95% CI 0.32-0.98; p = 0.04). This current study found no significant between-group difference in the incidence of permanent hypoparathyroidism (8.3% vs. 8.5%; p ≥ 0.99), suggesting that day 1 PTH < 10 pg/mL may only be predictive of transient hypoparathyroidism.…”

Use of pre-operative calcium and vitamin D supplementation to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy: a systematic review

“…Nine trials met the inclusion criteria (Figure 1 and Table 1). [16][17][18][19][20][21][22][23][24] They included a total of 912 patients. The trials were published between 2006 and 2019, spanning 14 years.…”

“…All nine trials studied adult populations in surgical in-patient departments, with follow up in out-patient clinics. Two trials were based in Italy, 18,24 two were in Pakistan 17,22 and the others were in India, 20 the USA, 21 Malaysia, 23 Australia 16 and France. 19 Six trials studied patients undergoing total thyroidectomy only: one included patients who had near total thyroidectomy, 20 where less than 1 ml of the thyroid gland is spared excision; one included patients who had completion thyroidectomy (removal of remnant thyroid tissue following less than total thyroidectomy); 16 and one included patients undergoing near total and subtotal thyroidectomy (sparing 3-5 g of thyroid tissue).…”

“…Two trials were based in Italy, 18,24 two were in Pakistan 17,22 and the others were in India, 20 the USA, 21 Malaysia, 23 Australia 16 and France. 19 Six trials studied patients undergoing total thyroidectomy only: one included patients who had near total thyroidectomy, 20 where less than 1 ml of the thyroid gland is spared excision; one included patients who had completion thyroidectomy (removal of remnant thyroid tissue following less than total thyroidectomy); 16 and one included patients undergoing near total and subtotal thyroidectomy (sparing 3-5 g of thyroid tissue). 17 Indications for surgery included both malignant and benign thyroid disease in eight trials, [16][17][18][19][20][22][23][24] whereas one trial exclusively studied patients with Graves' disease.…”

Role of Preoperative Calcium and Vitamin D Therapy to prevent Post-thyroidectomy Hypocalcemia

“…After excluding conference abstracts (n = 135), non-human studies (n = 108), and non-English studies (n = 49), we assessed 315 abstracts for eligibility. After we reviewed 26 full-text articles, four studies that included 381 patients were eligible for this analysis [14][15][16][17]. The details of the study-selection process are depicted as a ow chart (Figure 1).…”