Severe Postoperative Hypocalcaemia Research Articles

#1807 Use of teriparatide to prevent severe hypocalcemia after parathyroidectomy in dialysis-dependent patients: a feasibility study

Abstract Background and Aims Hungry bone syndrome is a common postoperative complication after parathyroidectomy (PTx) for severe secondary hyperparathyroidism (SHPT). We aimed to conduct a feasibility study to assess the potential impact of teriparatide on the course of postoperative hypocalcemia after PTx in dialysis-dependent patients. Method We performed a randomized controlled pilot study in 20 dialysis-dependent patients with severe SHPT undergoing total parathyroidectomy with autotransplantation of parathyroid tissue. Patients were randomized to receive either 20 mcg teriparatide (Forsteo) subcutaneously on day 1 after surgery in addition to standard postoperative care (n=11) or standard postoperative care alone (n=9). Severe postoperative hypocalcemia was defined as an ionized serum calcium level of less than 0.8 mmol/l during the first 3 days after surgery. Results Patients in the two groups did not differ in terms of pre- and postoperative laboratory data, including PTH, corrected total calcium, ionized calcium and alkaline phosphatase levels – Table 1. Severe hypocalcemia was observed in 6 patients in the teriparatide group (55%) and in 4 patients (44%) in the control group (p=0.99). The proportion of patients with symptoms of hypocalcemia was higher in patients not receiving teriparatide (67% vs 27%, p=0.17), although these differences did not reach statistical significance. All post-PTx patients received standard supplementation according to local protocol, including calcium carbonate 20 gr/day, active vitamin D 2 mcg/day per os, and intravenous calcium gluconate supplementation on demand for symptoms of hypocalcemia (e.g. numbness, tingling, or cramps). Total elemental calcium requirement after surgery (which may serve as a surrogate for the severity of hungry bone syndrome) was higher in patients receiving standard treatment alone (41 [Q1-Q3: 33; 49] grams per hospitalization vs 33 [Q1-Q3: 25; 40] grams in the teriparatide group, p=0.0375) – Fig. 1. The total length of hospital stay was 4 ± 1 days in teriparatide group and 5 ± 2 in control group, p=0.36. Conclusion In dialysis-dependent patients after PTx, we observed a trend towards an alleviation of postoperative hypocalcemia after single injection of teriparatide in addition to routine care. Further studies with larger sample sizes are needed to confirm these preliminary results.

Significant role of 1,25-dihydroxyvitamin D on serum calcium levels after total thyroidectomy: a prospective cohort study.

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. Serum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery. 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. 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.

Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,» resulting in severe and persistent postoperative hypocalcemia. To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT. The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy. There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p&lt;0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)). Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.

Pre-operative Cinacalcet Administration Reduces Immediate Post-operative Hypocalcemia Following Total Parathyroidectomy in Severe Renal Hyperparathyroidism.

In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). Patients with severe RHPT (defined by PTH ≥ 100pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00mmol/L. Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n = 27; Group II, n = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49pmol/L vs Group II: 154 ± 45, p = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60pmol/L vs 154 ± 45, p < 0.001), higher post-operative calcium (p < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels (p < 0.05). Cinacalcet use for > 1year resulted in fewer severe post-operative hypocalcemia than non-users (p = 0.022, OR 0.242, 95% CI 0.068-0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17-7.77, p = 0.022). In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1year reduced severe post-operative hypocalcemia.

Frequency and Risk Factors of Permanent Hypoparathyroidism After Total Thyroidectomy: An Experience at a Tertiary Care Hospital in Pakistan.

Thyroid surgeries are among the most common operations performed in the world. Hypocalcemia following total thyroidectomy (TT) is a common complication that is sometimes difficult to correct. This study aims to determine the frequency of hypocalcemia and permanent hypoparathyroidism (PtHPT) following TT. A total of 363 patient records were reviewed who underwent TT for any reason. Thirty-eight patients did not have a follow-up in the clinic in the postoperative period and were excluded from the final analysis with the final sample as 325. For patients who developed hypocalcemia during the postoperative hospital stay, their lowest calcium levels were recorded and medical records were reviewed for the period of one year for the requirement of oral calcium and active form of vitamin D (calcitriol or alpha calcidiol) in the outpatient setting. Patients who required calcium and vitamin D supplementation for up to 1year were labeled as having PtHPT. Risk factors were analyzed among those who developed PtHPT. From a total of 325 patients postoperative hypocalcemia developed in 163 (50.2%) patients, and 162 (49.8%) patients remained normocalcemic. Permanent hypoparathyroidism was found in 42(12.9%) patients and transient HPT in 121 (37.2%). Age, severe postoperative hypocalcemia (PoHC), and readmission for hypocalcemia were independent risk factors for PtHPT. Transient hypoparathyroidism (THPT) is common in our setup. Patients who develop severe hypocalcemia postoperatively and need readmission should be closely followed for the development of PtHPT.

Prediction Model of Postoperative Severe Hypocalcemia in Patients with Secondary Hyperparathyroidism Based on Logistic Regression and XGBoost Algorithm.

Objective A predictive model was established based on logistic regression and XGBoost algorithm to investigate the factors related to postoperative hypocalcemia in patients with secondary hyperparathyroidism (SHPT). Methods A total of 60 SHPT patients who underwent parathyroidectomy (PTX) in our hospital were retrospectively enrolled. All patients were randomly divided into a training set (n = 42) and a test set (n = 18). The clinical data of the patients were analyzed, including gender, age, dialysis time, body mass, and several preoperative biochemical indicators. The multivariate logistic regression and XGBoost algorithm models were used to analyze the independent risk factors for severe postoperative hypocalcemia (SH). The forecasting efficiency of the two prediction models is analyzed. Results Multivariate logistic regression analysis showed that body mass (OR = 1.203, P = 0.032), age (OR = 1.214, P = 0.035), preoperative PTH (OR = 1.026, P = 0.043), preoperative Ca (OR = 1.062, P = 0.025), and preoperative ALP (OR = 1.031, P = 0.027) were positively correlated with postoperative SH. The top three important features of XGBoost algorithm prediction model were preoperative Ca, preoperative PTH, and preoperative ALP. The area under the curve of the logistic regression and XGBoost algorithm model in the test set was 0.734 (95% CI: 0.595~0.872) and 0.827 (95% CI: 0.722~0.932), respectively. Conclusion The predictive models based on the logistic regression and XGBoost algorithm model can predict the occurrence of postoperative SH.

MO815: Cinacalcet Does not Prevent Severe Hypocalcemia After Parathyroidectomy in Dialysis-Dependent Patients

Abstract BACKGROUND AND AIMS Surgical treatment of secondary hyperparathyroidism (SHPT) is often followed by the rapid development of hypocalcemia, which is also known as hungry bone syndrome. We aimed to evaluate if preoperative use of cinacalcet may help to prevent severe hypocalcemia after parathyroidectomy (PTx) for SHPT in dialysis-dependent patients during the early postoperative period. METHOD The retrospective analysis included 616 patients who underwent PTx (either subtotal or total PTx with autotransplantation of parathyroid tissue) for SHPT between 2011 and 2019 in the single tertiary care center of endocrine surgery. Data on severe hypocalcemia development were available for 559 of the patients, 172 of them received cinacalcet before surgery. The median age of the patients was 49 (IQR 40–56) years and the median dialysis duration was 94 (IQR 56–142) months. Preoperative parathyroid hormone level was 153 pmol/L (IQR 105–223), total serum Ca was 2.44 mmol/L (IQR 2.24–2.61) and alkaline phosphatase was 283 IU/l (IQR 157–645). Severe postoperative hypocalcemia was defined as a serum ionized Ca level &amp;lt;0.9 mmol/L on the second or third day post-PTx. We also assessed need for intravenous (IV) calcium supplementation and the duration of in-hospital stay (≤7 days or &amp;gt;7 days) as surrogate markers of hungry bone syndrome severity. RESULTS Among patients treated with cinacalcet, 55.8% (n = 96) received 30 mg/day, 33.1% (n = 57)received 60 mg/day, 10.5% (n = 18) received 90 mg/day and 0.6% (n = 1) received 120 mg/day. Prevalence of severe hypocalcemia was less in patients who received 90 or more mg of cinacalcet a day, although this difference did not reach statistical significance (P = .1038) (Figure 1A). Use of cinacalcet (yes/no) was not associated with the risk of severe postoperative hypocalcemia: RR = 1.047 [95% confidence interval (95% CI) 0.946–1.146], OR = 1.229 (95% CI 0.801–1.886), P = .3837. A total of 54% of the patients were administered with IV calcium. Preoperative use of cinacalcet did not reduce the risk of IV calcium supplementation need: RR = 0.93 (95% CI 0.79–1.09), OR = 0.86 (95% CI 0.61–1.21); P = .3749. Among patients supplemented with IV calcium, medians of total Ca amount did not differ between those who received pre-PTx cinacalcet and those who did not: 6 (IQR 3–15) g versus 6 (IQR 4–10) g, respectively, P = .3981. Patients who received 60 mg of cinacalcet a day or more were more likely to require higher amounts of total IV Ca (Figure 1B), but this was not statistically significant [RR = 1.4 (95% CI 0.83–2.4); P = .2138]. In terms of length of hospital stay, we did not find differences between patients received 30, 60 and ≥ 90 mg of cinacalcet a day (P = .1285) (Figure 1C). Use of cinacalcet was not associated with prolonged (&amp;gt;7 days) in-hospital stay: RR = 0.863 (95% CI 0.708–1.04), OR = 0.765 (95% CI 0.546–1.081); P = .1417. CONCLUSION We found no evidence of a protective effect of preoperative cinacalcet use, neither on the prevalence nor on the severity of hypocalcemia development after PTx for SHPT in dialysis patients.

MO816: Bone Turnover Markers as Risk Factors of Severe Hypocalcemia After Parathyroidectomy for Secondary Hyperparathyroidism

Abstract BACKGROUND AND AIMS Hungry bone syndrome is a common postoperative complication after parathyroidectomy (PTx) for severe secondary hyperparathyroidism (SHPT). We aimed to evaluate whether preoperative levels of serum alkaline phosphatase (AP) and β-crosslaps (CTX) are associated with the development of severe hypocalcemia after PTx for SHPT in dialysis-dependent patients. METHOD The retrospective study included 127 severe SHPT dialysis-dependent patients who underwent subtotal (SPTx) or total parathyroidectomy with autotransplantation of parathyroid tissue (PTx + AT) in a single high-volume centre of endocrine surgery between 2011 and 2014. Severe postoperative hypocalcemia was defined as an ionized serum calcium level &amp;lt;0.9 mmol/L on a day 3 after surgery. RESULTS Severe hypocalcemia was observed in 83 (65.4%) patients after PTx. Comparing to those with mild hypocalcemia, hypoCa patients were significantly younger (mean age 44.2 ± 11.3 years versus 49.7 ± 10.4 years in a non-hypoCa group; P = .0089). Patients in two groups did not differ in terms of gender (P = .198), dialysis vintage (P = .24) and type of surgery (TPTx + AT or SPTx; P = .127). Preoperative PTH level was significantly higher in hypoCa group comparing to non-hypo Ca group [134 (Q1–Q3: 103–190) pmol/L versus 93.9 (Q1–Q3: 74.6–124.3) pmol/L, respectively; P &amp;lt; .0001]. In univariate analysis preoperative AP level was associated with the risk of postoperative severe hypocalcemia [363.2 (Q1–Q3: 180.9–726.3) IU in hypoCa group versus 142.1 (Q1–Q3: 97.2–223.7) IU in non-hypoCa group; P &amp;lt; 0.0001) (Figure 1). AP level above the cut-off value of 238.5 IU/L caused a 5-fold increase risk of severe hypocalcemia. We observed a moderate negative correlation between preoperative AP level and serum ionized calcium level on the third postoperative day after PTx {ρ = –0.637 [95% confidence interval (95% CI) –0.51 to –0.74]; P &amp;lt; .0001}. In contrast, preoperative CTX level was not associated with postoperative severe hypocalcemia [5.34 (Q1–Q3: 4.06–6.03) µg/L in hypoCa group versus 4.6 (Q1–Q3: 3.42–5.69) µg/L in non-hypoCa group; P = .191] (Figure 2). Moreover, the correlation between preoperative AP and CTX levels was weak, even though it was statistically significant [ρ = 0.27 (95% CI 0.08–0.44); P = .006]; and we observed no statistically significant correlation between preoperative CTX and PTH levels (P = .07). The multivariate logistic regression revealed AP level as the only independent risk factor of severe hypocalcemia development after PTx [ОR 1.006 (95% CI 1.002–1.009) per each IU; P = .005]. CONCLUSION We identified serum AP level, but not CTX, as an independent risk factor of severe hypocalcemia development after surgical treatment of SHPT. The correlation between CTX and other bone turnover markers (PTH, AP) is weak in dialysis-dependent patients with severe SHPT.

Effect of Preoperative Vitamin D Deficiency on Hypocalcemia in Patients with Acute Hypoparathyroidism after Thyroidectomy.

Postoperative hypoparathyroidism is a common complication of total or completion thyroidectomy. The association between preoperative vitamin D deficiency (VDD) and the development of more severe postoperative hypocalcemia is still unclear. Objectives. To evaluate the effect of preoperative VDD on severity of hypocalcemia in patients with hypoparathyroidism following thyroidectomy. Methods. Patients who developed acute hypoparathyroidism after total or completion thyroidectomy, defined as postoperative parathyroid hormone (PTH) level <15 pg/mL and albumin-adjusted calcium level <8.6 mg/dL, were prospectively recruited. Patients were divided into two groups according to their preoperative vitamin D status (VDD group: 25-hydroxyvitamin D (25(OH)D) level <20 ng/mL; non-VDD group: 25(OH) level ≥20 ng/mL). The primary outcome was severity of hypocalcemia in postoperative hypoparathyroidism. Significant hypocalcemia was defined as calcium level ≤7.5 mg/dL. Results. Forty-three patients (21 VDD, 22 non-VDD) were enrolled. Serum total albumin-adjusted calcium level was significantly lower in the VDD group (7.71 ± 0.5 vs. 8.16 ± 0.4 mg/dL, p < 0.01), and the incidence of symptomatic hypocalcemia was significantly higher in the VDD group (43% vs. 9%, p=0.01). The median maximal daily supplementary dose of elemental calcium was significantly higher in the VDD group (2,400 vs. 1,500 mg/day, p=0.02). Length of hospital stay was nonsignificantly longer in the VDD group (p=0.06). Preoperative vitamin D level <19.6 ng/mL could predict significant and symptomatic hypocalcemia in postoperative hypoparathyroidism with sensitivity of 90% and 82% and specificity of 70% and 69%, respectively. Conclusion. VDD is an independent risk factor for both significant and symptomatic hypocalcemia in hypoparathyroidism patients after thyroid surgery.

MON-LB058 Mediastinal Parathyroid Adenoma Presenting as a Neuroendocrine Tumor

Introduction: Tertiary hyperparathyroidism caused by renal failure can lead to ectopic parathyroid tissue hyperplasia creating a diagnostic challenge. Here we describe a case of mediastinal parathyroid hyperplasia presenting as a neuroendocrine tumor. Case Presentation: A 40-year-old male presented for endocrine workup of a possible mediastinal paraganglioma. At age 22 he was diagnosed with resistant hypertension followed by rapidly progressive renal failure. Hemodialysis was initiated following a failed kidney transplant at age 30. He was treated by nephrology for secondary hyperparathyroidism with calcitriol and cinacalcet and serum calcium was within the normal range. Parathyroid hormone (PTH) was 598 pg/mL (12-65 pg/mL). The patient developed shortness of breath and a right pleural effusion while awaiting a second transplant and a CT of the chest was completed. This revealed a 3.1x4.0x5.0 cm heterogenous mediastinal mass within the superior thorax, medial to the proximal thoracic esophagus, and posterior to the trachea at the level of T2. It did not communicate with the thyroid gland. An FNA of the mass showed cohesive groups of atypical cells with small uniform nuclei and a moderate amount of chromatin arranged in nests and acini. No mitotic figures were identified. Cells were positive for chromogranin and focally for CK7, and negative for CK20, synaptophysin, and TTF-1. Cytology was interpreted as a well differentiated neuroendocrine tumor/typical carcinoid. A Galium-68 DOTATATE scan revealed moderate tracer uptake in the mass only. His endocrine workup was notable only for a mildly elevated chromogranin A with normal serum catecholamines, calcitonin, and serotonin, as well as normal adrenal cortical function. The patient underwent thoracotomy with mediastinal mass resection. He developed severe postoperative hypocalcemia treated with calcium infusion and increased calcitriol doses. Pathology revealed a low-grade neuroendocrine tumor consistent with parathyroid hyperplasia with at least one lymph node positive for involvement. The tumor showed positive staining for PTH, chromogranin, and synaptophysin with Ki67 <1%. Conclusion: This case demonstrates a rare occurrence of mediastinal parathyroid hyperplasia related to tertiary hyperparathyroidism of renal failure. Early calcitriol replacement and PTH level monitoring represents the mainstay of prevention of tertiary hyperparathyroidism. Severe post-op hypocalcemia is a hallmark of disease and more extensive immunostaining of mediastinal masses should be applied in cases suggestive of parathyroid etiology, especially in patients with long-standing renal failure. Despite a low Ki67, lymph node involvement suggests the possibility of parathyroid carcinoma. Follow-up Gallium-68 DOTATATE scan and parathyroid scan are imperative to evaluate for recurrence or residual disease. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Perioperative hyperkalemia in hemodialysis patients undergoing parathyroidectomy for renal hyperparathyroidism.

The present study investigates the incidence of perioperative hyperkalemia and the influence factors of serum potassium levels during and after parathyroidectomy (PTX) in hemodialysis patients with renal hyperparathyroidism (rHPT). A total of 204 hemodialysis patients with refractory rHPT undergoing successful total parathyroidectomy with autotransplantation (tPTX + AT) were analyzed retrospectively. Hyperkalemia was defined as serum potassium levels ≥ 5.5mmol/L. The preoperative baseline level of serum potassium (K base+ ) was defined as a mean of the three preoperative prehemodialysis serum potassium levels. The higher levels of serum potassium during and immediately after surgery were recorded as K d0+ and the peak prehemodialysis serum potassium levels 3days after surgery as K d3+ . 136/204 (66.7%) patients suffered from hyperkalemia during or immediately after surgery and 65/204 (31.9%) patients were affected with prehemodialysis hyperkalemia 3days after surgery. K base+ was the only influencing factor for K d0+ . Serum K base+ , preoperative serum alkaline phosphatase, and total calcium supplement dosage during intravenous calcium supplement were the influencing factors for K d3+ . In the case of PTX, the serum potassium levels of patients with higher serum K base+ and severe postoperative hypocalcemia need to be monitored with extended attention perioperatively.

Risk factors and clinical course of hungry bone syndrome after total parathyroidectomy in dialysis patients with secondary hyperparathyroidism

BackgroundHungry bone syndrome (HBS) is an important postoperative complication after parathyroidectomy for severe secondary hyperparathyroidism (SHPT). There is, however, little data in the literature on its detailed clinical course, and the associated risk factors remain controversial.MethodsWe did a single-center retrospective study on 62 consecutive dialysis patients who underwent total parathyroidectomy for SHPT to examine the risk factors, clinical course and outcome. Data on demographic characteristics, perioperative laboratory parameters including serum calcium, phosphate, alkaline phosphatase (ALP) and parathyroid hormone (PTH), drug treatment for SHPT and operative details of parathyroidectomy were collected.ResultsSeventeen (27.4%) patients developed severe postoperative hypocalcemia with HBS. The serum calcium dropped progressively while serum ALP rose after operation until 2 weeks later when serum calcium reached the trough and serum ALP peaked. Serum phosphate also fell but stabilized between 4 and 14 days. The total postoperative calcium and vitamin D supplementation was significantly larger, and hospital stay was significantly longer in the group with HBS as compared with those without HBS. Young age, high body weight, high preoperative ALP level, and low preoperative calcium level independently predicted the development of HBS while preoperative PTH and use of cinacalcet or paricalcitol did not.ConclusionHBS was common after total parathyroidectomy in patients with SHPT, and it is important to closely monitor the postoperative serum calcium, phosphate and ALP levels in the following 2 weeks, especially for those at risk. The implications of our findings on perioperative management are discussed.

What is the prevalence of severe post-operative hypocalcaemia in patients who have undergone parathyroid surgery or a total thyroidectomy at the RVI, Newcastle? Does vitamin D play a role?

What is the prevalence of severe post-operative hypocalcaemia in patients who have undergone parathyroid surgery or a total thyroidectomy at the RVI, Newcastle? Does vitamin D play a role?

Parathyroid Hormone as a Marker for Predicting the Severity of Hypocalcaemia Following Parathyroidectomy.

The purpose of this study is to determine preoperative predictors of the severity of the hypocalcaemia following parathyroidectomy. The case records of 70 patients who underwent parathyroidectomy for primary hyperparathyroidism from 2000 to 2013 was retrospectively studied. Their symptoms at presentation, biochemical parameters serum calcium, parathyroid hormone, alkaline phosphatase and parathyroid size on ultrasound were compared with their serial post-operative serum calcium levels at 24, 48, 72 and 96h. For the purpose of analysis, patients were divided into three groups. Group 1-asymptomatic, biochemically normal (serum calcium always ≥8.5mgs%); Group 2-asymptomatic, biochemically below normal (at least one reading <8.5, but none <8.0); Group 3-symptomatic (any one reading <8.0). No correlation was found between the severity of the presenting symptoms, pre-operative serum calcium levels or the parathyroid size with the post-operative calcium levels in the three groups. Though preoperative serum alkaline phosphatase levels were higher in Group 3, it was not statistically significant (p=0.069). However, preoperative serum parathyroid hormone levels significantly correlated with postoperative serum calcium levels in all three groups (p=0.006). Pre-operative serum parathyroid hormone levels may serve as a marker for severe post-operative hypocalcaemia and thus identify patients requiring closer monitoring and longer hospitalization following parathyroidectomy.

Primary hyperparathyroidism after Roux-en-Y gastric bypass.

Primary hyperparathyroidism (PHPT) in the setting of previous roux-en-Y gastric bypass (RYGBP) is not well described. The diagnosis can be difficult, as secondary hyperparathyroidism (SHPT) commonly occurs in patients after RYGBP due to calcium malabsorption and vitamin D deficiency. All patients from 2000 to 2012 who underwent cervical exploration for diagnosis of primary hyperparathyroidism with history of preceding RYGBP were identified and analyzed retrospectively. Ten patients were identified. The average age was 58.4 and all patients were female. Time interval between RYGBP and cervical exploration was 67 months with median follow-up of 19 months. Average preoperative calcium was 10.8 mg/dL, PTH 155 pg/mL, and 25-vitamin-D 32 ng/mL. Eighty percent of patients presented with symptoms and 90% underwent preoperative imaging. Seventy percent underwent initial focused parathyroidectomy with 20% being converted to four-gland exploration. Seventy percent of patients had a single adenoma with two patients having multi-gland disease. Intraoperative PTH was used in seven patients with successful drop to 50% of baseline in all. Ninety percent of patients had greater then 6-month follow-up without evidence of persistent or recurrent PHPT. Average 6-month calcium was 9.3 mg/dL, PTH 73 pg/mL, and 25-vitamin-D 44 ng/ML. Four patients had evidence of persistently elevated PTH despite normalization of calcium. PHPT after RYGBP is rare but surgery with either a focused approach following successful localization or four-gland exploration is indicated when the biochemical diagnosis holds true. The presence of SHPT can make diagnosis and follow-up difficult and may predispose them to severe post-operative hypocalcemia.

Hungry Bone Syndrome after Parathyroidectomy for Primary Hyperthyroidism

Parathyroidectomy is the treatment of choice in patients with primary hyperparathyroidism (PHPT). This disease affects calcium metabolism at the level of bone tissue and renal tubules, resulting in hypercalcaemia, often asymptomatic, associated with hypophosphataemia and hypomagnesaemia. Sudden suppression of parathyroid hormone (PTH), caused by successful parathyroidectomy, in patients with preoperative high levels of PTH and hypercalcaemia from enhanced bone turnover, may induce severe postoperative hypocalcaemia that may lead to symptoms of tetany. This relatively uncommon condition is known as “hungry bone syndrome” (HBS), because it is believed to be due mainly to enhanced bone formation. Several risk factors have been advocated for HBS, and the syndrome is reported to be more likely to rise in subjects with severe preoperative bone disease. Other modifiable risk factors are preoperative vitamin D deficiency and high PTH and calcium levels. Treatment of HBS is basically the administration of high amounts of calcium immediately after the onset of postoperative hypocalcaemia. Supplements of active metabolites of vitamin D, as well as magnesium in depleted subjects are complementary in supporting bone remineralization. Oral supplementation may be requested for months after parathyroidectomy. Prevention is poorly documented, but it is reasonable to propose the correction of vitamin D deficit and the use of bisphosphonates aimed to lower PTH levels and bone resorption before parathyroidectomy.

Predictive Factors for Postoperative Severe Hypocalcaemia after Parathyroidectomy for Primary Hyperparathyroidism

Hypocalcaemia is a complication of parathyroidectomy. We retrospectively analyzed data on patients who underwent parathyroidectomy for primary hyperparathyroidism (pHPT) to identify predictive factors for severe postoperative hypocalcaemia. Since 2004 we performed 87 parathyroidectomies for pHPT. We divided the patients into two groups: subjects who presented with postoperative hypocalcaemia (group B) or otherwise (group A). We looked for a correlation between several variables and the incidence of postoperative hypocalcaemia. The median calcemia in group B (19 patients) was 6.9 mg/dL on the first postoperative day and 7.6 mg/dL on the third day. We observed hypocalcemia related clinical symptoms in every patient. In all 19 cases the reduction of intraoperative parathyroid hormone above 85 per cent after parathyroidectomy was related to the development of severe postoperative hypocalcaemia (P = 0.042). We found that the reduction of intraoperative parathyroid hormone over 85 per cent after parathyroidectomy can be considered a reliable predictive factor of postoperative hypocalcaemia after parathyroidectomy for primary hyperparathyroidism.

Post-surgery severe hypocalcemia in primary hyperparathyroidism preoperatively treated with zoledronic acid

Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of malignancy. Although the safety and efficacy of this drug in treating hypercalcemia associated with hyperparathyroidism have not yet been established in clinically controlled trials, its off-label use is not uncommon. We describe a patient with primary hyperparathyroidism treated with zoledronic acid who developed severe postoperative hypocalcemia. A 64-yr-old woman was admitted with severe hypercalcemia. She was treated with rehydration, calcitonin, methylprednisolone, furosemide as well as 4 mg/day of zoledronic acid for two consecutive days. Primary hyperparathyroidism caused by a right inferior parathyroid lesion was diagnosed. While awaiting surgery, she continued furosemide, methylprednisolone and hydration: after one week, serum calcium had fallen to such a low level that a short-term calcium carbonate supplementation was required. Three weeks after admission, the patient underwent selective right inferior parathyroidectomy, followed by reduction of PTH. During the postoperative period the patient presented severe hypocalcemia resistant to the usual treatment. Serum calcium levels returned to normal three months after surgery. The severity of hypocalcemia and the resistance to conventional treatments suggest that the effect of hungry bone syndrome could be worse in patients treated with bisphosphonates in the preoperative phase.

Severe Graves' Ophthalmopathy may be a Risk Factor for the Development of Postthyroidectomy Hypocalcaemia

The aim of this study was to compare the rate of hypocalcaemia after thyroid resection in patients with versus patients without Graves' Ophthalmopathy (GO). 153 patients following thyroid surgery for Grave's disease were studied. Patients were divided into three groups according to the severity of GO at the time of surgery using the NOSPECS classification. Subgroup I comprised of 70 patients without GO, subgroup II comprised of 63 patients with moderate GO and 20 patients with severe GO were assigned to Subgroup III. Association between severe ophthalmopathy and postoperative hypocalcaemia after thyroidectomy was investigated. 12/70 patients complained transient and 3/70 permanent hypocalcemia within subgroup I. 14/63 patients developed transient and 4/63 patients permanent hypocalcaemia within subgroup II. There were 7/20 patients with transient and 5/20 cases with permanent hypocalcaemia in the patient group with severe GO (subgroup III). The incidence of permanent postthyroidectomy hypocalcaemia was significantly higher in the subgroup III with severe GO when compared to the subgroup I without GO (p=0.004). Although postthyroidectomy hypocalcemia seems to be a multifactorial phenomenon, this study implicates unknown role of severe GO at time of surgery in the development of hypocalcaemia after thyroid surgery for Graves' disease. Therefore, patients with GO should be considered for surgery at high volume centres specialised in thyroid and parathyroid surgery.

Skin Necrosis After Intravenous Calcium Chloride Administration as a Complication of Parathyroidectomy for Secondary Hyperparathyroidism: Report of Four Cases

Intravenous (i.v.) calcium chloride is usually given to treat symptomatic hypocalcemia; however, the extravasation of calcium solution may cause soft tissue and skin necrosis. After parathyroidectomy and autotransplantation for secondary hyperparathyroidism associated with end-stage renal failure, i.v. calcium infusion is often necessary to treat severe postoperative hypocalcemia. We reviewed 371 patients who underwent parathyroidectomy for secondary hyperparathyroidism between January 2000 and June 2005, 96 of whom received i.v. calcium postoperatively for symptomatic hypocalcemia. We report the cases of three (3%) of our own patients and of one patient referred to our hospital, who suffered skin necrosis after i.v. calcium solution administration. These reports show that i.v. calcium should be administered into large veins, or via a central line, and diluted in an appropriate volume of solution. Moreover, the calcium solution infusion should be ceased if the patient complains of tenderness over the injection site. If skin necrosis develops, we suggest early debridement and a simple split thickness skin graft to repair the skin defect. We report our experience to remind surgeons of the danger of calcium chloride injection and to discuss ways of preventing and treating this complication.