Hypocalcaemia is a well-known postoperative complication of thyroidectomy. Consistent with the incidence of hypocalcaemia ranging from 19 to 38% reported by a meta-analysis and several recent publications [1, 8, 9], laboratory hypocalcaemia was found in 23.8% of patients in this retrospective study. Although hypocalcaemia is often asymptomatic, some clinical symptoms including tingling, numbness, or carpopedal spasm can also be seen, which can limit the routine daily activities of such patients. Symptomatic hypocalcemia was found in 12.8% of patients, which is also consistent with previous studies . In addition, the present study showed that preoperative vitamin D deficiency, especially severe vitamin D deficiency, is associated with an increased risk of postoperative hypocalcaemia.
Vitamin D plays a vital role in the regulation of PTH and calcium . It increases serum calcium by directly increasing calcium absorption from the intestine and bone resorption, and regulating the secretion of PTH from the parathyroid glands [11, 12]. Thus, preoperative vitamin D may exert a profound effect on the perioperative kinetics of calcium and PTH postthyroidectomy . When parathyroid function is impaired, sufficient vitamin D can promote the absorption of intestinal calcium and maintain calcium homeostasis. However, preoperative vitamin D deficiency damaged the regulatory mechanism in patients undergoing total thyroidectomy [14, 15], which increased the incidence of postoperative hypocalcaemia and led to hypoparathyroidism due to parathyroid ischaemia/injury or inadvertent resection. Several studies [16, 17] reported that as the vitamin D level decreased, the calcium level decreased statistically significantly while PTH increased. However, significant associations were not found in the current study. This may be due to the limited sample size in our study as we did not aim to explore the association of preoperative vitamin D levels with calcium and PTH levels.
In previous studies, many different cutoff levels for vitamin D have been explored to predict the risk of postoperative hypocalcaemia. We used three widely accepted cutoff levels of 10, 20, and 30 ng/mL and found that the incidence of postoperative hypocalcaemia was significantly higher for patients with 25-OHD < 10 ng/mL than for those with 25-OHD > 30 ng/mL. Our results are consistent with many previous studies. Al-Khatib and colleagues performed multivariate analysis on 213 patients undergoing total and completion thyroidectomy and showed that severe vitamin D deficiency, defined as serum 25-OHD < 10 ng/ml, was an independent predictor of postoperative hypocalcaemia . A prospective study conducted by Kirkby-Bott et al. reported a dose-dependent relationship between vitamin D level and the risk of hypocalcaemia as hypocalcaemia in patients with vitamin D levels < 10 ng/ml was significantly more likely than hypocalcaemia in patients with vitamin D levels > 20 ng/ml (32% vs. 13%, P < 0.025) . Another prospective study conducted by Daglar et al. indicated that the patients who had < 10 ng/mL vitamin D levels (severe deficiency) developed significantly more biochemical and clinical hypocalcemia than the patients with serum vitamin D levels higher than 10 ng/mL (P = 0.030 and P < 0.001, respectively) . However, some studies have reported diverse results. Two studies conducted by Griffin et al.  and Lang et al  found no correlation between vitamin D levels and the risk of postoperative hypocalcaemia using vitamin D cutoffs of both 10 and 20 ng/mL . The reasons for these conflicting results could be related to differences in the populations as well as patients’ individual characteristics.
As patients with hypocalcaemia may require longer hospitalization, more biochemical studies, extended pharmacological treatments, and additional medical resources, hypocalcaemia has become a burden for the health care system. Thus, some authors have recommended routine supplementation with calcium or vitamin D. A systematic review indicated that 7 out of the 9 trials included reported statistically significantly reduced rates of postoperative laboratory hypocalcaemia (absolute risk reduction, 13–59%) and symptomatic hypocalcaemia (absolute reduction, 11–40%) following preoperative supplementation . In several guidelines, for patients with a laboratory confirmed vitamin D deficiency (i.e., 25-OHD < 20 ng/ml), an age- and body weight- dependent therapeutic dosage was recommended to be used for 1–3 months; the dosage should be as follows (with ranges dependent on body weight): for neonates 1,000 IU/day; for infants 2,000–3,000 IU/day; for children and adolescents aged 1–18 years 3,000–5,000 IU/day; for adults and the elderly 7,000–10,000 IU/day or 50,000 IU/week . Previous studies have shown that treatment with vitamin D3 (cholecalciferol) takes three to five days to raise serum 25-OHD [21, 22]. In contrast, a single oral dose of calcifediol can generate the needed 25-OHD concentration within four hours [22, 23]. Considering that both D3 and 25-OHD enter immune cells to generate calcitriol, using the combination of D3 (medium-term) and calcifediol (immediate) is cost-effective and leads to the best clinical outcome .
Limitations of this study include its retrospective design and findings. Some preoperative and postoperative parameters might be missing, such as data on hypocalcaemia symptoms. In addition, the risk of permanent hypocalcaemia cannot be evaluated due to the lack of long-term follow-up of serum calcaemic levels.
In conclusion, preoperative vitamin D deficiency (25-OHD < 20 ng/mL), especially severe vitamin D deficiency (25-OHD < 10 ng/mL), is an independent predictive factor of postoperative hypocalcaemia after total thyroidectomy. Routine supplementation of vitamin D using the combination of D3 (medium-term) and calcifediol (immediate) with an age- and body weight- dependent therapeutic dosage is recommended for patients with vitamin D deficiency, especially severe vitamin D deficiency, thereby reducing postoperative hypocalcaemia.