Significant Hypocalcemia Research Articles

Is Preoperative Vitamin D Deficiency a Risk Factor for Postoperative Symptomatic Hypocalcemia in Thyroid Cancer Patients Undergoing Total Thyroidectomy Plus Central Compartment Neck Dissection?

Although some studies have reported that preoperative vitamin D deficiency (VDD) is a risk factor for hypocalcemia after total thyroidectomy (TT) in patients with nontoxic multinodular goiter or Graves' disease, the association between VDD and postoperative hypocalcemia in thyroid cancer patients undergoing TT plus central compartment neck dissection (CCND) remains unclear. This study evaluated whether preoperative VDD was associated with postoperative symptomatic hypocalcemia. Data were collected prospectively between September 2012 and May 2013. A total of 267 consecutive thyroid cancer patients who underwent TT with CCND were analyzed. Patients were divided into two groups--VDD or non-VDD--by preoperative vitamin D level of <10 or ≥10 ng/mL. Symptomatic hypocalcemia was defined as serum calcium <8.2 mg/dL and symptoms or signs of hypocalcemia. The rates of postoperative symptomatic hypocalcemia and clinicopathological features were compared between the two patient groups. The rate of postoperative symptomatic hypocalcemia was higher in the VDD group than in the non-VDD group (43.8% vs. 30.4%, p=0.043). By logistic regression analysis, predictive factors for postoperative symptomatic hypocalcemia included a preoperative vitamin D level of <10 ng/mL (p=0.007; odds ratio=3.00). In patients who had postoperative intact parathyroid hormone (iPTH) levels <15 pg/mL, symptomatic hypocalcemia was more common in the VDD group than in the non-VDD group (77.5% vs. 53.2%, p=0.008). The findings show that a preoperative vitamin D threshold level of >20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% when compared with patients with VDD (p=0.003). VDD is significantly associated with postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing TT plus CCND. VDD was predictive for symptomatic hypocalcemia when patients had postoperative serum iPTH levels <15 pg/mL. Thus, preoperative supplementation with oral vitamin D should be considered to minimize postoperative symptomatic hypocalcemia.

Canine hypoparathyroidism: case report

Primary hypoparathyroidism is an uncommon endocrinopathy in dogs, resulting from absolute or relative deficiency in the secretion of parathormone (PTH). The dog presented signs of hypocalcemia, including muscular spasms, tetany and cramps, evolving to tonic-clonic seizures and fever. Emergency therapy for hypocalcemia included glucose physiological solution at 0.45% and calcium gluconate administered intravenously. Diagnosis was confirmed by the presence of hypocalcemia, hyperphosphatemia and a decrease in parathormone (PTH).

Simultant operations on thyroid and parathyroid glands and their influence on the appearance of postoperative hypocalcaemia

Purpose of the work is to evaluate the rate of co­­existence of thyroid and parathyroid glands abnor­malities (mostly – primary hyperparathyroidism (PHPT) on the own clinical surgical thyroid practice, and to estimate the risk of postoperative hypocalcaemia ac­­cor­­­ding to different extent of simultaneous operations.Materials and Methods. During 2006-2011 years 5261 patients with different thyroid pathology were operated: 2170 with nodular goiter, 745 – with Graves’ disease, 2324 – with thyroid cancer and 22 – with Ha­­shimoto thyroiditis. Totally 4321 thyroidectomies and 940 hemithyroidectomies were performed. All patients were undergone screening of serum calcium. In case of elevated or upper-normal calcium concentration of parathormone was explored. Postoperative calcium and signs of hypocalcaemia were monitored post­ opera­­tively among different groups of patients. Results. Hypercalcaemia and upper-normal serum calcium were observed in 241 (4.4%). Farther in­­ vestigation revealed PHPT у 218 patients (4.1%). Dif­ferent extent of surgery and various types of mutual localization of thyroid and parathyroid lesions bring different risks of postoperative hypocalcaemia: from 44% up to 92%.Conclusion. PHPT is not rare coexistent disease in thyroid surgery (more than 4%). Simultaneous ope­rations increase the risk of postoperative hypo­calcaemia. The most prominent risk and severity of hypocalcaemia were observed for total thyroidectomy and single parathyroidectomy – 84 %, or hemi­thyroid­ectomy and contrlateral single parathyroidectomy – 85-92 %. It demand the relevant prognostic evaluation and prophylactic measures.

Intact PTH measurement 1 hour after total thyroidectomy as a predictor for patients at risk for developing symptomatic hypocalcaemia

Postoperative hypocalcaemia is one of the most common complication observed in patients undergoing total thyroidectomy with a report incidence ranging from 1.6% to 50%. Transient hypocalcaemia occur in upto 50% patients and permanent hypocalcaemia in 2%.Symptoms appear usually between 2 nd to 5 th postoperative day. In the absence of any reliable predictors of clinically relevant hypocalcaemia after total thyroidectomy, prolonged hospitalization to monitor serum calcium concentrations has been considered the standard of cure. To minimize postoperative complications and to permit an early and safe discharge, it is important to identify various methods to predict patients at high risk of developing significant hypocalcaemia , who are candidates for early treatment and patient at low risk who can be discharged early from hospital. We reviewed our experience in Yenepoya Medical College with 22 total thyroidectomies to determine the threshold value of 1 hour post total thyroidectomy iPTH level that can identify those at high risk for developing symptomatic hypocalcaemia. This is a prospective study done from sept 2012 to sept 2013.Based on our observations we concluded that, a 1 hour postoperative serum intact PTH 90% for predicting patients at risk for developing post total thyroidectomy symptomatic hypocalcaemia.

Histological Changes in Calcium Regulating Endocrine Gland (Ultimobranchial) After Dimethoate Exposure in Freshwater Catfish &amp;lt;i&amp;gt;Heteropneustes Fossilis&amp;lt;/i&amp;gt;

Ultimobranchial gland in fishes is associated primarily with calcium regulation. The study was aimed to find effect of an organophosphate pesticide dimethoate on serum Ca2+ and ultimobranchial gland in freshwater catfish Heteropneustes fossilis. Fish were exposed to dimethoate at 2.24 mg/l (75% of 96 h LC50) for short-term (24, 48, 72 and 96 h), and 25% of 96 h LC50 (1.00 mg/l) for long-term (6, 12, 24 and 36 d). The blood samples collected at assigned durations from the anaesthetized fish were used to measure serum Ca2+ levels. At the same time UBG were also extricated from the fish by removing the tissues adjoining esophagus, liver and sinus venosus of the heart for subsequent histological examination. A significant (P<0.05) increase in serum Ca2+ levels of fish following 24 h and 6d dimethoate exposure was observed. However, after 48 h and 12 d the Ca2+ level gradually begins to decline exhibiting significant (P<0.0001) hypocalcaemia after 96 h and 36 d in the exposed fishes. The histological examination of exposed fish glands exhibit significant changes in their cellular activity, staining property, nuclear diameter and nuclear volume, vacuolization and degeneration. It is concluded that dimethoate severely hampers the calcium homeostasis in Heteropneustes fossilis; therefore the pesticide should be cautiously used near aquatic bodies.

Early predictors of hypocalcemia after total thyroidectomy: an analysis of 304 patients using a short-stay monitoring protocol.

Postoperative hypocalcemia is common after total thyroidectomy, and perioperative monitoring of serum calcium levels is arguably the primary reason for overnight hospitalization. Confidently predicting which patients will not develop significant hypocalcemia may allow for a safe earlier discharge. To examine associations of patient characteristics with hypocalcemia, duration of hospitalization, and postoperative intact parathyroid hormone (IPTH) level after total thyroidectomy. Retrospective study of consecutive patients who underwent total thyroidectomy by a single high-volume surgeon between February 1, 2010, and November 30, 2012. Postoperative serum 25-hydroxyvitamin D (vitamin D), calcium, and IPTH levels were tested within 6 to 8 hours after surgery. Mild hypocalcemia was defined as any postoperative serum calcium level of less than 8.4 to 8.0 mg/dL. Significant hypocalcemia was defined as any postoperative serum calcium level of less than 8.0 mg/dL or the development of hypocalcemia-related symptoms. Total thyroidectomy. Associations of patient demographic and clinical characteristics and laboratory values with postoperative mild and significant hypocalcemia were examined using univariate analysis, and independent predictors of hypocalcemia, duration of hospitalization, and IPTH level were determined using multivariate analysis. Overall, 304 total thyroidectomies were performed. Mild and significant hypocalcemia occurred in 68 (22.4%) and 91 (29.9%) patients, respectively, of which the majority were female (P = .003). The development of significant hypocalcemia was associated with postoperative IPTH level (P < .001). On multivariate analysis, males had a decreased risk of developing mild (odds ratio, 0.37 [95% CI, 0.16-0.85]) and significant (odds ratio, 0.57 [95% CI, 0.09-0.78]) hypocalcemia. Every 10-pg/mL increase in postoperative IPTH level predicted a 43% decreased risk of significant hypocalcemia (P < .001) and an 18% decreased risk of hospitalization beyond 24 hours (P = .03). Presence of malignant neoplasm carried a 27% risk of mild hypocalcemia (P = .02). There was a progressively increasing risk of lower IPTH levels for each parathyroid gland inadvertently resected or autotransplanted. Male sex and African American race were independently predictive of higher IPTH levels. Low postoperative IPTH level, female sex, and presence of malignant neoplasm are all significant, independent predictors of hypocalcemia after total thyroidectomy. Clinicians should consider these variables when deciding how to best manage or prevent postoperative hypocalcemia.

Safety of Denosumab (Dmab) in Patients (Pts) with Stage 4 or Stage 5D Chronic Kidney Disease (Ckd)

ABSTRACT Aim: DMAB is a human monoclonal antibody that binds to RANK ligand to inhibit osteoclast-mediated resorption and is approved to prevent skeletal-related events in pts with bone metastases from solid tumors. DMAB-induced inhibition of bone resorption may impact calcium (Ca) homeostasis, affecting serum Ca levels. This study evaluated the incidence of hypocalcemia and safety parameters of pts with stage 4 or 5D CKD who were administered two subcutaneous (SC) doses of DMAB. Methods: Patients received two 120 mg doses of SC DMAB 28 days apart and were followed until day 113. All pts were required to have controlled secondary hyperparathyroidism and receive oral supplementation of ≥500 mg Ca and 400 IU vitamin D daily. The primary endpoint was the incidence of clinically significant, albumin-adjusted, serum Ca levels Results: 31/32 enrolled pts received 2 DMAB doses (15 stage 4; 16 stage 5D); 1 stage 4 CKD pt received 1 dose before withdrawing consent. 50% of pts were men, 78% white, and the median age was 76 years. The incidence of clinically significant hypocalcemia and adverse events at any point in the study are shown (Table). The majority (∼97%) of hypocalcemic events were mild to moderate in severity. The mean maximal serum DMAB concentrations were similar between the stage 4 and 5D CKD groups, 10.5 vs 8.17 µg/mL after dose 1 and 16.1 vs 14.5 µg/mL after dose 2. Patients (%) Stage 4 N=16 Stage 5D N=16 All N=32 Clinically significant hypocalcemiaa 1 (6.3) 2 (12.5) 3 (9.4) All AEs 10 (62.5) 15 (93.8) 25 (78.1) Hypocalcemia 3 (18.8) 10 (62.5) 13 (40.6) Hypomagnesmia 0 (0.0) 0 (0.0) 0 (0.0) Hypophosphatemia 0 (0.0) 1 (6.3) 1 (3.1) aSerum Ca levels Conclusions: While the use of DMAB was generally well tolerated in pts with stage 4 or 5D CKD, hypocalcemia events occurred despite oral Ca and vitamin D supplementation. This suggests an important role of bone resorption for the maintenance of serum Ca levels in this pt population, even among those with controlled secondary hyperparathyroidism. Stage 5D CKD pts were more likely to experience clinically significant or symptomatic hypocalcemia than stage 4 CKD pts. Use of DMAB in patients with stage 4 or 5D CKD requires careful monitoring for hypocalcemia. Disclosure: G. Block: Advisor for Amgen National Advisory committee (paid) and Steering Committee. Research grants and travel reimbursement from Amgen Inc.; O. Egbuna: Employed by Amgen Inc and owns shares of Amgen stocks. No other disclosures.; S. Zeig: Research funding from Amgen Inc. No other disclosures.; P. Pergola: Have an advisory relationship with Amgen, Keryx, ZS Pharma. Received research support from Amgen. No other disclosures; A. Braun: I was employed by Amgen Inc and own Amgen Inc stocks; Y. Yu: I am employed by Amgen Inc and own Amgen Inc stocks; W. Sohn: I am employed by Amgen Inc and own Amgen stocks; D. Padhi: I am employed by Amgen Inc and own Amgen Inc stocks. All other authors have declared no conflicts of interest.

Validity of early parathyroid hormone assay as a diagnostic tool for sub-total thyroidectomy related hypocalcaemia.

To determine the validity of early (one hour postoperatively) parathyroid hormone (PTH) assay (² 10 pg/ml), keeping gold standard as the serum ionic calcium level, for predicting sub-total thyroidectomy-related hypocalcaemia and to calculate the sensitivity and specificity of latent signs of tetany. Cross-sectional validation study. Department of General Surgery, Pakistan Institute of Medical Sciences, Islamabad from August 2008 to August 2010. Patients undergoing sub-total thyroidectomy were included by convenience sampling. PTH assay was performed 1 hour post sub-total thyroidectomy. Serum calcium levels were performed at 24 and 48 hours, 5th day and 2 weeks after surgery. Cases that developed hypocalcaemia were followed-up for a period of 6 months with monthly calcium level estimation to identify cases of permanent hypocalcaemia. Symptoms and signs of hypocalcaemia manifesting in our patients were recorded. Data was analyzed through SPSS version 10. 2 x 2 tables were used to calculate sensitivity and specificity of PTH in detecting post-thyroidectomy hypocalcaemia. Out of a total of 110 patients included in the study, 16.36% (n=18) developed hypocalcaemia including 1.81% (n=2) cases of permanent hypoparathyroidism. The sensitivity of one hour postoperative PTH assay as a predictive tool for post-thyroidectomy related hypocalcaemia was 94.4% while its specificity was 83.6% with 53% positive predictive value and 98.7% negative predictive value. One hour post sub-total thyroidectomy PTH assay can be helpful in predicting post sub-total thyroidectomy hypocalcaemia. Moreover, it can be useful in safe discharge of day-care thyroidectomy patients.

Whole blood versus serum ionized calcium concentrations in dialysis patients

Background/AimsThe aim of this study is to measure the difference of ionized calcium between heparinized whole blood and serum.MethodsWe recruited 107 maintenance hemodialysis (HD) patients from our hospital HD unit. The clinical and laboratory data included ionized calcium in serum and in whole blood (reference, 4.07 to 5.17 mg/dL).ResultsThe level of ionized calcium in serum was higher than that in whole blood (p < 0.001). Bland-Altman analysis showed that difference for ionized calcium was 0.5027. For the difference, the nonstandardized β was -0.4389 (p < 0.001) and the intercept was 2.2418 (p < 0.001). There was a significant difference in the distribution of categories of ionized calcium level between two methods (κ, 0.279; p < 0.001).ConclusionsThis study demonstrates that whole blood ionized calcium is underestimated compared with serum ionized calcium. Positive difference increases as whole blood ionized calcium decreases. Therefore, significant hypocalcemia in whole blood ionized calcium should be verified by serum ionized calcium.

Protective effect of selected calcium channel blockers and prednisolone, a phospholipase-A2 inhibitor, against gentamicin and carbon tetrachloride-induced nephrotoxicity

The ameliorative effect of calcium channel blockers (CCBs) and a phospholipase-A2 inhibitor in drug-/chemical-induced nephrotoxicity was investigated. Rats were divided into 7 groups of 5 rats in each group. In the gentamicin model, group I rats were pretreated with normal saline (10 ml kg(-1)), while groups II-VII rats were pretreated with normal saline (10 ml kg(-1)), ascorbic acid (10 mg kg(-1)), nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)), respectively, perorally 1 h before intraperitoneal (i.p.) injection of gentamicin (40 mg kg(-1)) for 14 days. In the carbon tetrachloride (CCl4) model, rats were pretreated with CCBs and prednisolone for 7 days before inducing nephrotoxicity with 20% CCl4 (1.5 ml kg(-1)). Rats were thereafter killed and blood and tissue samples were collected for assessments. I.p. injections of gentamicin and CCl4 caused significant hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia, and hyperchloremic alkalosis and reduced renal tissue levels of antioxidants. Also, significant reductions in the hemoglobin, packed cell volume, red blood cells, and platelet indices were observed. Pretreatments with nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)) significantly ameliorated the deleterious effects of gentamicin and CCl4 possibly via antioxidant and anti-lipoperoxidation mechanisms. The results obtained in this study suggest potential clinical usefulness of tested CCBs and prednisolone in drug-/chemical-induced nephrotoxicity.

Does the Osteoporosis Dose of Denosumab Really Cause Clinically Significant Hypocalcaemia in CKD 4 and 5

Denosumab is a potent novel antiresorptive agent for treatment of osteoporosis with unique mechanism of action . It is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Initially denosumab appeared particularly promising for patients with advanced stages of renal failure but over the past two years several publications questioned that, reporting adverse effects and especially severe hypocalcaemia. Aim of the Study: to investigate further the effect of the osteoporosis dose of denosumab on serum calcium levels in patients with CKD 4 and CKD 5. Methods: This retrospective outpatient study included 17 females with CKD 4 and 5 who received a single or a multiple (at 6 months intervals) 60-mg subcutaneous dose of denosumab. Adjusted serum Calcium was measured prior to the dose and at various points of time after that. Results: Only two of the subjects developed clinically significant hypocalcaemia. Both of them were clearly inadequately supplemented with calcium and vitamin D. Conclusion: The results from the current study along with a critical analysis of the previous publications reveal that the vast majority of the previous reports were based on inadequately supplemented with calcium and vitamin D patients and that severe hypocalcaemia is unlikely in appropriately supplemented subjects, especially in the CKD 4 subgroup. However, due to the scarcity of data further research is warranted, Original Research Article British Journal of Medicine & Medical Research, 4(2): 649-659, 2014 650 especially in the CKD 5 subgroup. In the mean time more cautious approach rather than a blanket ban on denosumab appears to be the most appropriate policy in these two populations.

Does Preoperative 25‐Hydroxyvitamin D Status Significantly Affect the Calcium Kinetics after Total Thyroidectomy?

Although previous studies have suggested that low preoperative 25-hydroxyvitamin D (25-OHD) is a risk factor for hypocalcemia after total thyroidectomy, the impact of preoperative 25-OHD on calcium (Ca)/parathyroid hormone (PTH) kinetics in the immediate postoperative period remains unclear. The study compared the postoperative Ca/PTH kinetics between different preoperative 25-OHD levels. A total of 281 patients who underwent a total thyroidectomy were analyzed. Serum Ca was measured preoperatively within 1 h after surgery (Ca-D0) and on the following morning (Ca-D1). Preoperative 25-OHD was also measured after overnight fasting while postoperative PTH was checked at skin closure on day 0 (PTH-D0) and on the following morning on day 1 (PTH-D1). The Ca/PTH kinetics were compared between three groups (group I: preoperative 25-OHD < 10 ng/mL; group II: 25-OHD = 10-20 ng/mL; group III: 25-OHD > 20 ng/mL). Group I had significantly lower preoperative Ca (p = 0.016) and Ca-D0 (p = 0.036) but higher PTH-D1 (p = 0.015) than groups II and III. PTH-D0, Ca-D1, and the rate of clinically significant hypocalcemia were similar in the three groups. Group I had a significantly smaller Ca drop (-0.02 vs. 0.01 and 0.02 mmol/L, p = 0.011) and a tendency for a significantly smaller PTH drop (0.4 vs. 0.5 and 1.0 pmol/L, p = 0.073) than groups II and III. PTH-D1 (OR = 1.550) and 25-OHD (OR = 0.958) were independent factors for Ca drop from day 0 to day 1. Although group I began with lower serum Ca, those patients tended to have a greater PTH response to Ca drop and so preoperative 25-OHD did not significantly affect the overall Ca kinetics from preoperative to day 1.

A diabetic patient treated for hypertension develops tremors and twitches

Objective: To report an unusual but known cause of hypomagnesaemia-induced hypocalcaemia and review the relevant literature. Methods: We present the clinical and laboratory findings in a case of hypomagnesaemia induced-hypocalcaemia, and discuss the underlying mechanisms in light of the available literature. Results: After admission our patient described typical features of magnesium deficiency such as weakness, tremors and muscle twitches. He also had clinical signs of hypocalcaemia such as a pronounced carpal pedal spasm. Blood results revealed that he had low calcium and magnesium. This was further confirmed by another set of blood results. His vitamin D levels were normal at 25.2 pg/mL and 27.3 pg/mL. His parathyroid hormone was at 18.5 pg/mL (12–72). His urea and electrolytes were normal with sodium of 137 mmol/l, potassium of 3.8 mmol/l, creatinine of 93 mL/minute, and liver function tests in the normal range. Hypomagnesaemia is a common finding and has been reported to be present in nearly 12% of hospitalised patients. From a review of published reports, it is seen that most cases of hypomagnesaemia are due to gastrointestinal or renal losses, but it is also seen with excess alcohol consumption. Drugs such as proton pump inhibitors and, although not often reported, thiazide diuretics are known to cause hypomagnesaemia. The patient was on Indapamide for his hypertension. With replacement therapy, both his ion levels returned back to normal. Conclusion: Hypomagnesaemia is often usually associated with multiple biochemical abnormalities. The increasing use of diuretics and the introduction of potent preparations present a considerable risk for hypomagnesaemia induced-hypocalcaemia.

Post total thyroidectomy hypocalcemia

No single factor can predict the occurrence of post total thyroidectomy (TT) hypocalcemia. This study was conducted to look at various factors usually implicated in post TT clinically significant hypocalcemia (CSH) and to develop a scoring system using a combination of these factors to predict CSH. Prospective study, tertiary care center. 145 patients, who underwent total thyroidectomy for benign goiters and early carcinoma thyroid ( < T2/N0/M0), were included. Age of the patient, presence, or absence of hyperthyroidism, pre-operative levels of serum calcium and 25 OH vitamin D, post-operative iPTH at 8 hours and calcium at 12 hours, intra-operative parathyroid preservation status, and nodule size were studied. CSH prediction score (0 to 8) was designed based on these 8 factors. SPSS 13 software was used. For comparison between groups' independent samples T-test and Chi-square test was used. Statistical significance was set at P<0.05. A logistic regression analysis model was built to assess the significant predictors. There were 22 males and 123 females. 64.82% had euthyroid multinodular goiters, 24.82% had toxic MNG, and 10.34% had an early carcinoma of thyroid. 30.34% developed CSH. CSH was observed in patients with low pre-operative calcium (P=0.008), low 25 OH vitamin D (P=0.001), low post-operative iPTH at 8 hours (P=0.001), low serum calcium at 12 hours after surgery (P=0.001) and lesser number of parathyroid identification at surgery (P=0.001). Patient age (P=0.2) and nodule size (P - 0.17) was not significant. Hypocalcemia risk score of > 3 had 91% sensitivity, 84% specificity with a PPV of 71% and NPV of 95%, whereas score of ≥ 4 had 100% specificity and PPV in predicting CSH. CSH after TT is multi-factorial, and a combination of factors (Hypocalcemia prediction score > 3) can be used to predict it so as to discharge patients within 24 hours after surgery.

Simplified regional citrate anticoagulation using a calcium-containing replacement solution for continuous venovenous hemofiltration

Regional citrate anticoagulation (RCA) is not widely used because it requires complex therapeutic modalities, a specialized calcium-free replacement solution, and continuous intravenous calcium infusion. We designed a simplified protocol for RCA using a commercial calcium-containing replacement solution for continuous venovenous hemofiltration (CVVH). Thirty-six patients were treated with RCA-based pre-dilution CVVH using a calcium-containing replacement solution (ionized calcium 1.50mmol/L). We pumped a 4% trisodium citrate solution into the arterial line of extracorporeal circulation at a starting rate of 200mL/h while adjusting the rate to achieve a post-filter ionized calcium level of between 0.25 and 0.5mmol/L. The initial blood flow was set at 150mL/min. The replacement solution was delivered at 35mL/kg/h. We measured the serum and effluent citrate concentration during CVVH at 0, 24, 48, and 72h. The mean hemofilter survival was 61.3±21.6h (range 14-122h). The mean 4% trisodium citrate solution pumped was 207 (190-230)mL/h, and the mean pre-filter and post-filter ionized calcium levels were 0.96-1.02 and 0.34-0.38mmol/L, respectively. Ninety-two, 63, and 48% of the hemofilters were patent at 24, 48, and 72h. The mean serum citrate concentration was not significantly different at 24, 48, and 72h. No bleeding episodes were found, and no patient showed the symptoms and signs of hypocalcemia or citrate toxicity. Our simplified RCA protocol using a calcium-containing replacement solution for CVVH is effective and safe, and obviates the need for a separate peripheral or central venous catheter for continuous intravenous calcium infusion.

Adult onset recurrent seizures as the first presentation of primary hypoparathyroidism

Introduction: Hypoparathyroidism leading to hypocalcemia is an important treatable cause of recurrent seizures. Primary hypoparathyroidism presenting for the first time as seizures in adulthood is quite infrequent. Patients may present with hypocalcemic seizures even in the absence of subtle hypocalcemic signs. Case report: A 30 year old male, was presented to the emergency facility in an unconscious condition. He was intubated on the way to the hospital as he had suffered from two episodes of ventricular tachycardia. He had previous history of recurrent seizures for 6 years inspite of multiple anticonvulsants including phenytoin sodium, sodium valproate, and levetiracetam. The seizure frequency increased in the last year and he would have 5-6 episodes/ month. A MRI brain scan and EEG at the onset were both normal, as was the general examination but he had history of bilateral cataracts. There were no signs of tetany. Investigations revealed a normal hemoglobin and glucose level with normal electrolytes and both TLC and DLC levels were also normal. He had a serum calcium level of 3.3 mg% with a serum parathyroid hormone level of 1pg/ml, serum 25(OH) vitamin D levels of 6.6ng/ml and hypomagnesemia. NCCT head scan showed bilateral basal ganglia, and deep white matter calcification. Conclusions: 1) Ironically, increasing reliance on high end investigations such as a MRI brain scan could lead to certain conditions being missed; conditions that could be easily identifiable by the humble CT scan. 2) All treatable metabolic conditions should be excluded at first before commencing with anticonvulsants; this will restrict patients from burdensome polytherapy and related side effects.

Predicting the need for calcium and calcitriol supplementation after total thyroidectomy: Results of a prospective, randomized study

The optimal protocol for the detection and treatment of postthyroidectomy hypoparathyroidism is unknown. We sought to identify and treat patients at risk for symptomatic hypocalcemia on the basis of a single parathyroid hormone (PTH) obtained the morning after surgery (POD1). We performed a prospective, randomized study of total thyroidectomy patients who had POD1 calcium and PTH (pg/mL) levels. Randomization was determined by POD1 PTH: if ≥ 10, patients received no supplementation unless symptomatic; if <10, patients were randomized to calcium, calcium and calcitriol, or no supplementation. Of 143 patients, 112 (78%) had a POD1 PTH ≥ 10. Hypocalcemic symptoms were transiently reported in 11 (10%) and managed with outpatient calcium. Of 31 patients with PTH <10, 15 (48%) developed symptoms, including 5 who required intravenous calcium. On multivariate logistic regression analysis, when we adjusted for postoperative calcium level and performance of central neck dissection, we found that predictors of hypocalcemic symptoms were younger age (odds ratio 1.59, 95% confidence interval 1.07-2.32) and a PTH <10 (odds ratio 1.08, 95% confidence interval 1.04-1.12). There were no patient or treatment-related factors that predicted a POD1 PTH <10. A single POD1 PTH level <10 can accurately identify those patients at risk for clinically significant hypocalcemia. All total thyroidectomy patients with a postoperative PTH ≥ 10 can be safely discharged without supplementation. Given the small number of patients with PTH <10, it is unclear whether both calcium and calcitriol are needed for these higher-risk patients.

Magnesium Supplementation Does Not Affect Blood Calcium Level in Treated Hypoparathyroid Patients

Magnesium is involved in the homeostasis of calcium metabolism, and magnesium deficiency may lead to clinically significant hypocalcemia. We have had two cases in our department in which treated hypoparathyroid patients with stable calcium levels developed hypercalcemia in conjunction with supplementary magnesium use. To our knowledge, there has been no prospective study looking at the effect of supplementary magnesium on calcium homeostasis in hypoparathyroid patients. The aim of this pilot study was to evaluate whether magnesium treatment affects plasma calcium levels in hypoparathyroid patients. We conducted a prospective, two-phase, uncontrolled treatment trial at a referral center of endocrine disorders. We enrolled treated (calcium + vitamin D analog) hypoparathyroid patients with normal plasma magnesium levels. Three weeks of treatment with oral magnesium (350 mg/d) were followed by 2 wk off treatment. We compared the plasma ionized calcium level after 3 wk of treatment to the pretreatment value. Plasma calcium, phosphate, magnesium, and creatinine levels were measured before treatment, after 3 wk on magnesium, and 2 wk after stopping magnesium treatment. Ten patients completed the trial. Supplementary treatment with magnesium for 3 wk did not change calcium levels in these patients. Magnesium supplementation induced a small but statistically significant increase in the plasma magnesium level, but levels of phosphate and creatinine remained stable. Magnesium supplementation did not influence plasma calcium levels in treated hypoparathyroid patients.

Denosumab for the Treatment of Bisphosphonate-Refractory Hypercalcemia

Case Report A 52-year-old man with a history of metastatic renal cell carcinoma to the lungs presented with confusion and dehydration to the outpatient oncology department. The corrected-for-albumin serum calcium level was 13.9 mg/dL after treatment with zoledrenic acid for 4 months. The patient had no known bone metastasis, and the parathyroid hormone–related protein in his serum was 67 pg/mL, which was consistent with humoral hypercalcemia of malignancy, a frequent syndrome in renal cell cancer. The patient was admitted to the inpatient service, started on hydration, and a dose of zoledronic acid was administrated. The patient improved clinically, and a moderate reduction in the calcium levels was achieved. However, 1 week later, the patient worsened again clinically, and his calcium levels were rising. His hypercalcemia was responding only minimally to aggressive hydration and calcitonin administration when it was decided to use denosumab, which is a novel agent, off-label to treat the bisphosphonate-refractory hypercalcemia of the patient. Denosumab is currently approved for the prevention of skeletal-related events in patients with bone metastases from solid tumors. After the initiation of denosumab, the calcium level of the patient fell rapidly to normal levels within 2 days, which was durable for at least 1 month (Fig 1). Unfortunately, the patient experienced rapid disease progression and no additional treatments were administered. Discussion Zoledronic acid incorporates rapidly into the bone and is taken up by the resorptive activity of mature osteoclasts. Intracellularly, as a nitrogen-containing bisphosphonate, zoledronic acid acts principally as an inhibitor of farnesyl-pyrophosphate synthase, which reduces the prenylationand, therefore, theactivityofguanosine5 -triphosphate-binding proteins, which are critical to osteoclast function and survival. However, denosumabisanovel, fullyhumanmonoclonalantibody,whichprevents the receptor activator of nuclear factor kappa B ligand from binding to its receptor and inhibits osteoclast development, activation, and survival. Therefore, it is conceivable that denosumab has a more pronounced effect. Indeed, this notion was supported by data from phase III clinical trialsinwhichamorepronouncedsuppressionofbone-turnovermarkers was seen. At the same time, the propensity to cause significant hypocalcemia, presumably as a result of reduced osteoclast function, was significantly increased in patients treated with denosumab compared with patients treated with zoledronic acid. Hypocalcemia has emerged as one of the main adverse effects of this agent. Interestingly, Fizazi et al showed that a calcium decrease of grade 3 or higher occurred in 48 patients (5%) receiving denosumab and 13 patients (1%) receiving zoledronic acid, which demonstrated the potentially more potent effect of denosumab in malignant hypercalcemia. Other studies by Stopeck et al and Henry et al demonstrated similar effects. To our knowledge, this is the first reported case of management of malignant hypercalcemia in a solid tumor with denosumab. Currently, there is one ongoing clinical trial studying the use of denosumab for refractory hypercalcemia, and the results are pending.

Hypocalcemia Induced by Raloxifene

Raloxifene is an anti-resorptive agent used in postmenopausal osteoporosis. This is the first report of the occurrence of clinically significant hypocalcemia following raloxifene treatment in a patient with occult vitamin D deficiency. Since vitamin D deficiency is widely prevalent in the community, screening for vitamin D deficiency and its correction is advisable before the initiation of anti-resorptive therapy.