BACKGROUND: Iatrogenic hypoparathyroidism is a common cause of postthyroidectomy hypocalcaemia. It has varying incidence rates after neck surgery in Saudi Arabia, ranging from 0.07% to 65.30%. Hypoparathyroidism can manifest with a spectrum of symptoms, ranging from mild to severe and life-threatening. This study aimed to assess the rate and predictors of iatrogenic hypoparathyroidism after thyroid surgery and its natural course.
METHODS: This retrospective cohort study used a data collection form to extract patient information from the electronic healthcare system (Best-Care) for patients treated from 2017 to 2022. Patients\' demographics, surgical specifics and biochemical profiles were recorded for subsequent analysis.
RESULTS: Among the 343 patients who underwent thyroidectomy, 130 (37.9%) developed hypoparathyroidism, primarily within the first day after surgery. Calcium or vitamin D supplementation before surgery did not significantly influence hypoparathyroidism development. Notably, extensive combined lymph node dissection was significantly associated with postoperative hypoparathyroidism development (p = 0.0004). More patients who underwent central and lateral lymph node dissection (n = 19, 79.17%) developed hypoparathyroidism than patients who underwent central (n = 18, 40.91%) or lateral (n = 8, 38.10%) dissection alone. Permanent hypoparathyroidism was observed in 40 patients (11.66%).
CONCLUSIONS: This study revealed a high incidence of iatrogenic hypoparathyroidism and high rates of permanent hypoparathyroidism. Further research is warranted to better comprehend the risk factors and optimise management strategies for iatrogenic hypoparathyroidism. Overall, our findings emphasise the need for vigilant monitoring and effective management of patients undergoing thyroidectomy and the significance of postoperative replacement therapies.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters.
METHODS: A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH.
RESULTS: Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity.
CONCLUSIONS: Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.

The aim of this study was to evaluate the prevalence of severe hypocalcemia in patients attending the emergency department. Symptoms, causes, treatment, and outcome of severe hypocalcemia as well as course of calcium concentrations were assessed. This retrospective case series included all adult patients with measurements of serum calcium concentrations presenting to the emergency department of the Bürgerspital Solothurn between January 01 in 2017 and December 31 in 2020. Medical record reviews were performed of all patients with severe hypocalcemia, defined by a serum calcium concentration < 1.9 mmol/L, to assess clinical presentation and management. 1265 (3.95%) patients had a serum calcium concentration of < 2.1 mmol/L of which 139 (11%) had severe hypocalcemia of < 1.9 mmol/L. 113 patients had at least one measurement of albumin. Of these, 43 (3.4%) had an albumin-corrected serum calcium < 1.9 mmol/L defining true, severe hypocalcemia. Hypocalcemia was identified and documented in 35% of all cases. The mean serum calcium concentration was 1.74 ± 0.14 mmol/L. Calcium concentrations in malignancy-related hypocalcemia were similar to non-malignancy-related hypocalcemia. The main symptoms attributed to hypocalcemia were cardiac and neurologic. 12% of patients with severe hypocalcemia received intravenous and 23% oral calcium replacement. Active malignancy was the main cause of severe hypocalcemia in 28%, while in most cases, the main cause remained unclear. 41.9% of severely hypocalcemic patients reattended the emergency department for another episode of hypocalcemia within 1 year. Hypocalcemia is common in patients attending the emergency department, however, appears to be neglected frequently. The disorder is often a manifestation of severe disease, triggered by multiple causes. Calcium replacement was administered in less than half of the patients with severe hypocalcemia in this study. Due to frequent readmissions to the emergency department and a high mortality, increased awareness of the disorder and careful follow-up are desirable.

UNASSIGNED: Although active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)2D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)2D on calcium (Ca) concentrations after total thyroidectomy.
UNASSIGNED: Serum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery.
UNASSIGNED: Serum Ca, PTH, and 1,25(OH)2D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)2D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p<0.0001), with 28% of patients showing increases in 1,25(OH)2D. The only factor predicting a postoperative 1,25(OH)2D decrease was a high preoperative 1,25(OH)2D concentration. Postoperative 1,25(OH)2D concentrations, as well as the magnitude and rate of decrease from preoperative levels, showed strong positive correlations with preoperative 1,25(OH)2D concentrations (p<0.0001 for all three variables) but not with PTH concentrations. These findings suggest that 1,25(OH)2D concentrations after thyroidectomy were more strongly dependent on preoperative concentrations than on the effect of PTH decrease and were relatively preserved, possibly preventing sudden severe postoperative hypocalcemia. A high 1,25(OH)2D level was the most important preoperative factor for hypocalcemia (<2 mmol/L; p<0.05) on the first postoperative day; however, only PTH decrease was statistically significant (p<0.001) when intraoperative factors were added. In the PTH >10 pg/mL group, the decrease in 1,25(OH)2D levels was significantly associated with postoperative hypocalcemia (p<0.05). Similarly, in the PTH levels >15 pg/mL group, a decrease in 1,25(OH)2D concentration was a significant factor, and the amount of PTH decrease was no longer significant.
UNASSIGNED: 1,25(OH)2D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)2D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)2D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.

OBJECTIVE: To investigate the parathyroid function and calcium (Ca) levels in the secondary hyperparathyroidism (SHPT) state in patients with Graves\' disease.
METHODS: We examined 31 consecutive patients with Graves\' disease without chronic kidney disease, who were treated with total thyroidectomy. The patients were divided into a normal parathyroid hormone (PTH) group (NPTH group; n = 19) with a PTH level ≤ 65 pg/mL, and a secondary hyperparathyroidism group (SHPT group; n = 12), with a PTH level > 65 pg/mL. The PTH and Ca-related parameters were examined and the risk factors for postoperative hypocalcemia were analyzed.
RESULTS: The preoperative Ca level was significantly lower (2.24 ± 0.06 vs. 2.31 ± 0.07 mmol/L, p < 0.05) in the SHPT group than in the NPTH group. The reduction in PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D), and Ca levels from the preoperative day to the next morning was significantly greater in the SHPT group than in the NPTH group (p < 0.05). When intraoperative factors were included, the decrease in the PTH level alone was significant. SHPT was a significant factor in determining the extent of PTH reduction.
CONCLUSIONS: Hyperfunctioning parathyroid glands in the SHPT state were more susceptible to postoperative PTH reduction, which, combined with low preoperative Ca levels, increased the risk of postoperative hypocalcemia in patients with Graves\' disease.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function.
METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group).
RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period.
CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

To study the incidence and management of postoperative hypocalcemia in participants undergoing near-total (NTT) and total thyroidectomy (TT) at a tertiary health care center. This is an observational prospective study. Patients posted for NTT and TT in our institute and meeting the inclusion criteria were included. A total of 45 participants were enrolled. The serum calcium was measured on postoperative day 2, at the time of discharge and on 3 months follow-up. A combination of injectable and oral calcium supplements with or without vitamin D sachet was used for the treatment of hypocalcemia. Hypocalcemia was observed in 49% cases. Women were observed to develop hypocalcemia at a higher rate than men. Incidence of hypocalcemia was more in TT patients than NTT patients. Cases with malignant pathology were more susceptible to develop hypocalcemia than those with benign pathology. Operated TT with concomitant neck dissection were at higher risk for development of hypocalcemia. There was no significant association between age and incidence of hypocalcemia. Serum calcium measured on postoperative day 2 was a reliable indicator of risk of hypocalcemia. The early measurement of serum calcium level is a reliable indicator of the risk of hypocalcemia. Standardized treatment of hypocalcemic patients with calcium and vitamin D supplements can reduce the incidence and morbidity associated with postoperative hypocalcemia.

BACKGROUND: The added benefit of using near-infrared autofluorescence (NIRAF) during total thyroidectomy (TT) remains controversial. This study investigated whether or not NIRAF results in improved patient outcomes postoperatively.
METHODS: We analyzed 1711 TT patients, reported in nine randomized controlled trials, following a systematic search of five databases. NIRAF was compared to the standard of care (naked eye with/without white light). Outcomes included parathyroid gland (PG) and calcium parameters and other clinical outcomes. For dichotomous outcomes, the log odds ratio (logOR) was calculated, and for continuous outcomes, the crude mean difference (MD) was measured. Sensitivity analysis was performed when heterogeneity was significant. The revised Cochrane risk of bias tool was used to assess the methodological quality.
RESULTS: Compared to the standard of care, the use of NIRAF was associated with a significant reduction in postoperative hypoparathyroidism [logOR=-0.31; 95% CI: -0.57: -0.05], inadvertent PG removal [logOR=-0.93; 95% CI: -1.60: -0.26], and postoperative hypocalcemia [logOR=-0.43 mmol/l; 95% CI: -0.77: -0.09]. It was also associated with significantly higher postoperative PTH levels [MD=4.78 pg/ml; 95% CI: 2.13: 7.43], PG identification rate [logOR=1.02; 95% CI: 0.31: 1.72], postoperative serum calcium [MD=0.05; 95% CI: 0.00: 0.09], and operative time [MD=9.38 min; 95% CI: 6.68: 12.09]. No difference was seen regarding PG autotransplantation, length of hospital stay, and hospitalization due to hypocalcemia. Seven trials had low risk and the remainder had some concerns.
CONCLUSIONS: NIRAF is superior to the naked eye in identifying all four PGs during TT. The reduced risk of postoperative hypoparathyroidism and hypocalcemia reflected this preservation value. However, it was not associated with a change in the length of hospital stay. Although rare, the readmission rate due to hypocalcemia was similar across both methods.

UNASSIGNED: The specific impact on calcium dynamics after non-massive blood transfusions remains relatively unexplored. This study aimed to compare pre- and post-transfusion calcium levels in patients receiving blood and blood product in the emergency department.
UNASSIGNED: This is a single-center, prospective, cross-sectional study conducted at the Emergency Department of Gazi University Health Research and Application Center Hospital in Ankara, Turkey, from January 1, 2020, to August 31, 2020. The study included adult patients who underwent blood and blood product transfusions, and serum calcium levels were measured and compared from samples taken before and after transfusion.
UNASSIGNED: A total of 292 participants were enrolled in the study, with 242 participants included in the final analysis. The mean total calcium level was 8.41 ± 0.76 mg/dL before transfusion and 8.34 ± 0.71 mg/dL after transfusion (p=0.012). When examining the corrected calcium values after receiving blood products based on the type of blood products, participants who received apheresis platelets had a post-transfusion corrected calcium value of 8.26 ±0.41 mg/dL, with a pre-transfusion value of 9.09 ±0.49 mg/dL (p<0.01). The post-transfusion ionized calcium value for participants receiving apheresis was 1.04 ±0.08 mg/dL, compared to 1.15 ±0.09 mg/dL for those who did not receive apheresis (p=0.049). There was a significant relationship between receiving fresh frozen plasma and post-transfusion ionized calcium values (p=0.024).
UNASSIGNED: This study demonstrated that transfusion-associated hypocalcemia can occur even at mild levels in patients receiving blood and blood product transfusions in the emergency department. However, it is suggested that the clinical effects of hypocalcemia, even when occurring based on the type and quantity of blood products, are minimal and negligible.

BACKGROUND: Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment.
METHODS: We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis.
RESULTS: Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia.
CONCLUSIONS: Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.