Total thyroidectomy is a widely performed surgical procedure for benign and malignant thyroid disorders, including multinodular goiter, Graves’ disease, and Hashimoto’s thyroiditis. Despite advancements in operative techniques, postoperative hypocalcemia remains the most frequent complication, occurring in 30–50% of patients transiently and in 1–4% permanently [1]. The etiology is largely attributed to parathyroid gland injury, devascularization, or inadvertent removal during surgery, leading to impaired parathyroid hormone (PTH) secretion and disrupted calcium homeostasis [2]. Vitamin D is a critical regulator of calcium metabolism, enhancing intestinal calcium absorption and maintaining serum calcium levels. Deficiency in vitamin D has been postulated as a predisposing factor for postoperative hypocalcemia due to its effect on calcium balance and parathyroid reserve [3]. Several clinical trials have assessed whether preoperative vitamin D supplementation could reduce the incidence or severity of post-thyroidectomy hypocalcemia, but the results remain inconclusive [4,5]. The multifactorial pathophysiology of post-thyroidectomy hypocalcemia involves both surgical and patient-related factors. While surgical expertise, the extent of thyroidectomy, and meticulous preservation of parathyroid glands are critical, patient-specific parameters such as baseline vitamin D status, pre-existing parathyroid dysfunction, and calcium metabolism also play a significant role [6]. Understanding the association between preoperative vitamin D levels and postoperative hypocalcemia is therefore clinically important. Identifying patients at risk could help optimize perioperative management protocols, reduce complication rates, and improve recovery outcomes after thyroidectomy. This study was designed to evaluate the relationship between preoperative vitamin D3 levels and the occurrence of hypocalcemia following total thyroidectomy in patients with benign thyroid diseases, with the objective of refining patient selection and perioperative care strategies [7–10].

Study Design and Setting This was a prospective observational study conducted in the Department of General Surgery, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, between November 2022 and October 2023. Ethical approval was obtained from the Institutional Thesis Protocol Approval Committee (TAPC No. 750) and the Institutional Ethics Committee (IEC No. 1520). Written informed consent was secured from all participants prior to enrollment. Study Population Patients aged ≥18 years undergoing total thyroidectomy for benign thyroid diseases were consecutively recruited. Inclusion Criteria • Age >18 years. • Patients undergoing total thyroidectomy for benign thyroid conditions. • Willingness to provide informed consent. Exclusion Criteria • Age <18 years. • Preoperative hypocalcemia or primary hyperparathyroidism. • History of renal insufficiency. • Current use of medications affecting calcium metabolism (e.g., bisphosphonates, calcitonin, calcimimetics, RANKL inhibitors, SERMs, glucocorticoids). • Declined participation. Study Procedure Eligible patients were assessed preoperatively for demographic characteristics and baseline laboratory investigations. Serum 25-hydroxyvitamin D (25-OHD), calcium, and albumin levels were measured within one week of surgery. Laboratory Methods • 25-OHD: Measured using chemiluminescence immunoassay (Access Immunoassay Systems, Beckman Coulter Inc., USA). • Serum Calcium: Arsenazo III method (AU480 chemistry analyzer, Beckman Coulter, Ireland). • Serum Albumin: Bromocresol green method (AU480 chemistry analyzer, Beckman Coulter, Ireland). Adjusted serum calcium was calculated using the formula: Adjusted calcium = 0.8 × (4.0 – serum albumin) + serum calcium. Patients were categorized into four groups based on preoperative vitamin D status: • Severe deficiency: <10 ng/mL • Deficiency: 10–20 ng/mL • Insufficiency: 20–30 ng/mL • Sufficiency: >30 ng/mL Outcome Measures • Laboratory hypocalcemia: Adjusted serum calcium <8 mg/dL on any postoperative day. • Symptomatic hypocalcemia: Clinical features (e.g., paresthesia, tingling, carpopedal spasm) accompanied by laboratory hypocalcemia. Postoperative serum calcium levels were assessed at 6 a.m. on days 1, 2, and 3 following surgery. Surgical Technique All patients underwent a standardized total thyroidectomy. The procedure involved a collar incision, dissection along anatomical planes, ligation of superior and inferior thyroid vessels, careful identification and preservation of the recurrent laryngeal nerve and parathyroid glands, and complete removal of thyroid tissue. Haemostasis was secured, a drain placed, and wound closure performed in layers with subcuticular sutures. Vocal cord mobility was checked upon extubation. Statistical Analysis Data were entered into Microsoft Excel and analyzed using SPSS version 26 (IBM Corp., USA). Continuous variables were expressed as mean ± SD and compared using Student’s t test. Categorical variables were analyzed using Chi-square or Fisher’s exact test. A p-value <0.05 was considered statistically significant.

A total of 53 patients were screened during the study period (November 2022–October 2023), of which 12 were excluded. The final analysis included 41 patients undergoing total thyroidectomy for benign thyroid diseases. Demographic Characteristics The study cohort ranged in age from 24 to 75 years, with a mean age of 47.4 ± 11.7 years. The majority of patients (65.8%) were between 40 and 59 years. Females constituted a significant majority of the study population (83%), while males represented only 17%. Table 1. Distribution of age groups Age group (years) Number of patients (n=41) Percentage (%) 20–39 10 24.3 40–59 27 65.8 60–80 4 9.7 Preoperative Vitamin D Levels Vitamin D deficiency was highly prevalent. Only 26.8% of patients had sufficient levels (>30 ng/mL), while 73.2% were below the sufficiency threshold. Severe deficiency (<10 ng/mL) was observed in 7.3% of cases, deficiency (10–20 ng/mL) in 36.6%, and insufficiency (20–30 ng/mL) in 29.2%. Table 2. Preoperative vitamin D levels in patients undergoing total thyroidectomy Vitamin D level (ng/mL) No. of patients (n=41) Percentage (%) <10 3 7.3 10–20 15 36.6 20–30 12 29.2 >30 11 26.8 Postoperative Hypocalcemia The overall incidence of laboratory-confirmed hypocalcemia was 26.8% (11/41 patients). The distribution across vitamin D categories showed no statistically significant association (Fisher’s Exact test, p=0.953). The majority of cases occurred in patients with vitamin D deficiency (10–20 ng/mL) and insufficiency (20–30 ng/mL). Table 3. Postoperative hypocalcemia in relation to preoperative vitamin D levels Vitamin D level (ng/mL) Hypocalcemia absent Hypocalcemia present Total (%) <10 3 (7.3%) 0 (0%) 3 (7.3) 10–20 11 (26.8%) 4 (9.8%) 15 (36.6) 20–30 8 (19.5%) 4 (9.8%) 12 (29.2) >30 8 (19.5%) 3 (7.3%) 11 (26.8) Total 30 (73.2%) 11 (26.8%) 41 (100) Gender and Hypocalcemia Interestingly, all 11 cases of hypocalcemia occurred in female patients. None of the seven male patients developed hypocalcemia. However, this association did not reach statistical significance (p=0.33, Fisher’s Exact test). Table 4. Hypocalcemia and gender distribution Gender Hypocalcemia present Hypocalcemia absent Total (%) Male 0 7 (17%) 7 (17%) Female 11 (26.8%) 23 (56.2%) 34 (83%) Parathyroid Gland Preservation Preservation of parathyroid glands was significantly associated with postoperative calcium status (p=0.049). Patients with all four glands preserved had better outcomes, while those with fewer glands preserved showed higher rates of hypocalcemia. Table 5. Parathyroid gland preservation and postoperative hypocalcemia No. of parathyroid glands preserved Hypocalcemia present Hypocalcemia absent Total (%) 1 0 0 0 2 0 1 (2.4%) 1 (2.4%) 3 2 (4.9%) 0 2 (4.9%) 4 9 (21.9%) 29 (70.7%) 38 (92.7) Hospital Stay Duration Hospital stay ranged from 3 to 9 days. While no statistically significant difference was observed across vitamin D groups (p=0.161), patients with vitamin D deficiency and insufficiency showed a trend toward longer hospitalization. Table 6. Association between preoperative vitamin D levels and hospital stay Vitamin D level (ng/mL) 3 days 4 days 5 days 6 days 9 days <10 0 3 (7.3%) 0 0 0 10–20 1 (2.4%) 6 (14.6%) 6 (14.6%) 0 2 (4.9%) 20–30 4 (9.8%) 6 (14.6%) 1 (2.4%) 1 (2.4%) 0 >30 1 (2.4%) 4 (9.8%) 4 (9.8%) 2 (4.9%) 0

In the present prospective study of 41 patients undergoing total thyroidectomy for benign thyroid diseases, postoperative hypocalcemia occurred in 26.8% of cases. Although vitamin D deficiency was highly prevalent in the cohort (73.2%), no statistically significant correlation was found between preoperative vitamin D levels and the occurrence of postoperative hypocalcemia. These findings suggest that postoperative hypocalcemia is multifactorial, with surgical and patient-specific determinants playing more dominant roles than preoperative vitamin D status alone. The incidence of hypocalcemia in this study is consistent with previously reported ranges of 20–30% for transient hypocalcemia following thyroidectomy [11]. Permanent hypocalcemia is far less common, typically <2%, and was not observed in our study. Similar to our results, other investigations have demonstrated that while vitamin D deficiency may be prevalent among surgical patients, it does not invariably predict hypocalcemia. For instance, Cherian et al. found no significant association between preoperative 25-hydroxyvitamin D levels and postoperative calcium decline [12]. The disproportionate distribution of hypocalcemia among female patients in our series (all 11 cases) deserves attention. Although gender itself may not directly influence calcium homeostasis, several studies have reported higher rates of thyroid disorders and surgical complications among women, likely due to hormonal, anatomical, and disease-prevalence differences [13]. Nevertheless, the absence of statistical significance in our findings indicates that larger sample sizes are needed before attributing a definitive role to sex-based risk. Preservation of the parathyroid glands during surgery emerged as the most critical determinant of postoperative calcium status. Patients in whom all four parathyroids were preserved had significantly lower rates of hypocalcemia compared to those with fewer glands preserved (p=0.049). This observation aligns with multiple studies emphasizing the paramount importance of meticulous surgical technique in safeguarding parathyroid function [14]. Techniques such as capsular dissection, careful identification of parathyroid glands, and avoidance of thermal injury have been shown to reduce the risk of devascularization and inadvertent excision [15]. Vitamin D, being a key regulator of calcium absorption, has long been considered an important modifier of post-thyroidectomy outcomes. However, the literature remains conflicting. Some studies suggest that vitamin D deficiency predisposes patients to hypocalcemia due to a reduced compensatory ability of the gut to absorb calcium [16]. Conversely, other reports, in agreement with our findings, conclude that the immediate postoperative hypocalcemia is more directly attributable to surgical insult on the parathyroid glands rather than baseline vitamin D levels [17]. These discrepancies may reflect differences in patient populations, surgical expertise, and cutoff thresholds for vitamin D categorization. Another important consideration is the role of immediate postoperative monitoring. Our study measured serum calcium on postoperative days 1–3, a critical period for identifying transient hypocalcemia. Early recognition and supplementation can prevent symptomatic complications, which include carpopedal spasms, tetany, and, in severe cases, cardiac arrhythmias [18]. Standardized protocols involving early calcium and vitamin D supplementation for at-risk patients have been shown to reduce symptom burden and hospital readmissions [19]. In our series, although hypocalcemia was relatively common, all cases were transient and managed effectively, highlighting the benefit of close monitoring. Hospital stay in our study ranged from 3 to 9 days, with no statistically significant association between vitamin D status and duration of hospitalization. Nonetheless, patients with deficiency and insufficiency showed a tendency toward longer stays. Previous studies have also reported that prolonged hospitalization is more closely related to the severity of symptomatic hypocalcemia and the need for intravenous calcium therapy rather than baseline vitamin D levels [20]. Taken together, our findings support the view that while vitamin D deficiency is widespread and may contribute to impaired calcium metabolism, its predictive value for postoperative hypocalcemia is limited. Instead, meticulous surgical preservation of parathyroid glands remains the most effective strategy for reducing the incidence of hypocalcemia.

Post-thyroidectomy hypocalcemia remains a frequent complication, observed in 26.8% of patients in this study. Despite the high prevalence of vitamin D deficiency, no significant correlation was found between baseline vitamin D levels and postoperative hypocalcemia. Female patients were more frequently affected, though this association was not statistically significant. Importantly, parathyroid gland preservation demonstrated a clear protective role, underscoring the critical importance of surgical technique. While routine assessment and correction of vitamin D deficiency may offer overall health benefits, perioperative prevention of hypocalcemia should primarily focus on meticulous operative strategies and vigilant postoperative monitoring.

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