Corrected Serum Calcium Levels Research Articles

Evaluation of prognostic factors and the role of chemotherapy in unfavorable carcinoma of unknown primary site: a 10-year cohort study

BackgroundCarcinoma of unknown primary site (CUP) has a poor prognosis and the prognostic factors in these patients are not well established. Furthermore, there are no selection criteria for patients who should benefit from chemotherapy.MethodsThe medical records of 179 CUP patients who were treated at Taipei Veterans General Hospital from 2000 to 2009 were reviewed. Factors associated with survival were determined by Kaplan-Meier analysis. Differences between the groups with and without palliative chemotherapy were analyzed.ResultsUnivariate analysis revealed multiple prognostic factors, including performance status, lung metastasis, number of metastatic organs, serum albumin, corrected serum calcium, lactate dehydrogenase (LDH), sodium, and cholesterol levels, palliative chemotherapy, and white blood cell and lymphocyte counts. Multivariate analysis showed that performance status < 2, serum albumin level ≥ 3.5 g/dl, corrected serum calcium level < 10.7 mg/dl, single metastatic organ, and palliative chemotherapy were independent factors of better prognosis. Patients with better performance status, higher serum albumin, and lower serum LDH levels had significantly greater benefit from palliative chemotherapy.ConclusionsCertain patients with unfavorable CUP will have better survival. Identification of patients with unfavorable CUP who could benefit from palliative chemotherapy warrants future prospective studies.

Severe Hypercalcemia Following Vitamin D Supplementation in a Patient With Multiple Sclerosis

To describe a patient with multiple sclerosis (MS) who developed severe hypercalcemia, attributed to the additive effect of 5500 IU of cholecalciferol and 2020 mg of calcium daily. Case report. University hospital. A 58-year-old woman with MS and osteoporosis presenting with acute-onset tremors and confusion. Serum calcium and 25-hydroxyvitamin D levels. The patient's corrected serum calcium level was 15.2 mg/dL (reference range, 8.7-10.1 mg/dL; to convert to millimoles per liter, multiply by 0.25), and her 25-hydroxyvitamin D level was 103 ng/mL (to convert to nanomoles per liter, multiply by 2.496). The results of extensive laboratory tests to rule out hyperparathyroidism, malignant neoplasms, and other causes of hypercalcemia were unrevealing. It is common practice to prescribe high-dose cholecalciferol to MS patients for its possible role in immunomodulation and relapse-rate reduction. Nevertheless, cholecalciferol may increase serum calcium, and there seems to be an additive effect when patients simultaneously use calcium supplements. This case underscores the need for physicians to be attentive to the possibility of hypercalcemia in patients treated with both high-dose cholecalciferol and calcium.

Denosumab for Treatment of Hypercalcemia of Malignancy in Patients with Solid Tumors or Hematological Malignancies Refractory to IV Bisphosphonates: A Single-Arm Multicenter Study

Abstract 2483 Introduction:Hypercalcemia of malignancy (HCM) is a serious complication in patients with advanced cancer, including those with hematological malignancies. HCM is thought to largely result from tumor-driven increases in bone resorption. IV bisphosphonates (BP) are used for treatment of HCM, but patients may relapse after treatment or become refractory to IV BP treatment. In animal models of HCM, inhibition of RANK ligand (RANKL), the key mediator of bone resorption, reversed established HCM more effectively than BP. Denosumab (Xgeva®) is a fully human monoclonal antibody against RANKL. We present data from a planned interim analysis of a single-arm study evaluating the effect of denosumab treatment in patients with HCM who have not responded to recent BP treatment. Methods:Patients eligible for enrollment in this trial are those with confirmed solid tumors or hematologic malignancies, recent IV BP treatment (7 to 30 days prior), and corrected serum calcium (CSC) levels of > 3.1 mmol/L (12.5 mg/dL). Patients with benign hyperparathyroidism, hyperthyroidism, adrenal insufficiency, or on dialysis are ineligible. Patients receive a single subcutaneous injection of denosumab (120 mg) on study days 1, 8, 15, 28, and every 4 weeks thereafter. Evaluable patients are those who received ≥ 1 dose of denosumab. The primary endpoint is the proportion of responding patients, defined as a CSC level ≤ 2.9 mmol/L (11.5 mg/dL) by day 10 of treatment. Secondary endpoints include complete response (CSC ≤ 2.7 mmol/L [10.8 mg/dL] by day 10 of treatment), response duration, and safety. The interim analysis was planned after at least 10 denosumab-treated patients received ≥ 2 doses of denosumab and provided a serum sample at study day 10 for measurement of CSC level. This trial is registered at clinicaltrials.gov (NCT00896454) and is sponsored by Amgen Inc. Enrollment is ongoing for this trial. Results:To date, 15 patients have enrolled and received ≥ 1 dose of denosumab. Five patients have advanced stages of hematological malignancies (multiple myeloma, chronic lymphocytic leukemia, and non-Hodgkin’s lymphoma). The median baseline CSC level was 3.4 mmol/L (13.6 mg/dL). At day 10, 12 of the 15 patients (80%; 95% exact confidence interval [CI]: 51.9%, 95.7%) achieved a response, with a median decrease in CSC from baseline of 0.68 mmol/L (2.71 mg/dL). Among these 12 patients, the median duration of response was 28 days (95% CI: 7, not estimable) based on Kaplan-Meier estimates. A complete response was achieved by 10 of the15 patients (66.7%; 95% exact CI: 38.4%, 88.2%). Adverse events (AEs), serious AEs, and deaths were reported for 14, 12, and 8 patients, respectively, and were as expected in this population of patients with advanced cancer. Conclusions:Results from this interim analysis demonstrate that denosumab effectively lowers serum calcium in patients with HCM who did not or no longer respond to recent treatment with IV BP. These results suggest that denosumab may be an effective treatment for HCM in this challenging population. Disclosures:Hu:Amgen Inc.: Speaker. Off Label Use: Denosumab for treatment of hypercalcemia of malignancy. Gucalp:Eisai: Consultancy. Glezerman:Amgen Inc.: Research Funding. Ying:Amgen Inc.: Employment. Yeh:Amgen Inc.: Employment.

Influence of renin–angiotensin system on serum parathyroid hormone levels in uremic patients

The aim of this study was to investigate the factors influencing serum parathyroid (PTH) levels, including medications for treating chronic kidney disease-mineral and bone metabolism disorder (CKD-MBD) in patients with end-stage renal disease. We enrolled 1,076 patients in nine Japanese facilities who had begun hemodialysis (HD) due to ESRD. We investigated the relationships between intact PTH (iPTH) levels and clinical parameters and medications just prior to beginning HD. Significant decreases in serum iPTH levels were seen in males, in the presence of diabetes mellitus (DM), and with administration of renin-angiotensin system inhibitors (RASIs). Significant correlations were found between serum calcium and iPTH levels. In the patients administered RASIs, there was a significant decrease in serum iPTH levels with DM, male gender, and administration of active vitamin D sterols (VDs) compared with those not administered RASIs, although serum-corrected calcium levels were not different. Multiple regression analysis found gender, age, presence of DM, and serum calcium and phosphate levels to be significant contributing factors. In addition, administration of angiotensin II receptor blockers (ARBs) may also be a contributing factor to iPTH levels at the beginning HD (p=0.050). In this study, serum iPTH levels were related to administration of ARBs besides gender, age, the presence of DM and serum calcium levels. Our study suggests that the RA system involve serum iPTH levels in uremic patients.

Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma

BackgroundAnalysis of prognostic factors for progression-free survival (PFS) and overall survival (OS) was performed using final data from a randomized phase III trial of sunitinib versus interferon-α (IFN-α) as first-line metastatic renal cell carcinoma (RCC) therapy. DesignA multivariate Cox regression model analyzed baseline variables for prognostic significance. Each variable was investigated univariately and then multivariately using a stepwise algorithm. ResultsEach treatment arm comprised 375 patients. For sunitinib, multivariate analysis of PFS identified five independent predictors, including serum lactate dehydrogenase (LDH) level, presence of ≥2 metastatic sites, no prior nephrectomy, Eastern Cooperative Oncology Group (ECOG) performance status, and baseline platelet count, while multivariate analysis of OS identified serum LDH level, corrected serum calcium level, time from diagnosis to treatment, hemoglobin level, ECOG performance status, and presence of bone metastasis as predictors. For IFN-α, LDH level and presence of ≥2 metastatic sites were common predictors of PFS to those for sunitinib, as were all predictors of OS except ECOG status. ConclusionsThis analysis identified prognostic factors for PFS and OS with sunitinib as first-line metastatic RCC therapy and confirmed that the Memorial Sloan-Kettering Cancer Center model is applicable in the era of targeted therapy.

Fluctuation of Corrected Serum Calcium Levels Following Partial and Total Thyroidectomy

Objectives: To identify any fluctuation of corrected serum calcium levels and to determine the presence of sub-clinical hypocalcaemia following partial and total thyroidectomy with preservation of at least two parathyroid glands. Design: A prospective study. Setting: Tertiary Head & Neck referral unit. Patients: Eighty five patients undergoing partial or total thyroidectomy with or without laryngectomy from April 2003 to April 2009 were included in the study. Corrected serum calcium levels (CCSL) were noted preoperatively and postoperatively on day 1, day 7 and 6 months. Results: Forty six patients underwent hemi-thyroidectomy (HT), 29 underwent total thyroidectomy (TT) and 10 underwent total thyroidectomy with laryngectomy (TTL). Nine (19.56%) patients in the HT group, 6 (24.14%) in the TT group and 3 (30.0%) in the TTL group developed hypocalcaemia postoperatively which was most significant on 1st postoperative day. This improved by 7th postoperative day in each group when the change in calcium levels became statistically insignificant. Six patients (3 patients had HT, 2 had TT and 1 had TTL) developed sub-clinical mild hypocalcaemia which was persistent at 6 months follow-up. Conclusion: The most significant changes in corrected serum calcium levels occur within first 24 hours after thyroid surgery. Thereafter most patients return to normocalcaemia within a seven-day period. Despite preservation of parathyroid glands there is a subgroup of patients who develop sub-clinical hypocalcaemia which persists even at six months but does not require treatment.

Mineral and bone disease pattern in elderly haemodialysis patients

Although many studies have recently addressed the mineral and bone disorder of chronic kidney disease (CKD-MBD), only limited information is available for elderly dialysis patients. We prospectively collected serum phosphorus, calcium, parathyroid hormone (PTH), 25(OH) vitamin D, albumin, C-reactive protein, protein intake and CKD-MBD treatments in 9169 maintenance haemodialysis patients in France in June 2008. We then compared biological and treatment patterns in 3403 patients aged 75 or over to their younger counterparts. Elderly patients exhibited lower serum phosphorus and parathyroid hormone concentrations (-8 and -18%, respectively) but slightly higher corrected serum calcium levels (+2%) compared to patients aged below 75 years. Elderly patients had higher mean C-reactive protein, lower serum albumin levels and reduced protein intake. Calcium and non-calcium phosphate binders as well as cinacalcet usage and dosage were significantly reduced in elderly patients, with a trend towards lower active vitamin D derivatives usage. Elderly patients were better controlled according to the Kidney Disease Outcome Quality Initiative (K/DOQI) targets compared to patients aged below 75. In this large 2008 cohort of elderly haemodialysis patients, it appears easier to control serum parameters of CKD-MBD as compared to younger dialysis patients. A better control of serum phosphorus was observed, with less phosphate binder and reduced cinacalcet dosage.

Simultaneous production of parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF) in lung cancer patients with hypercalcemia and leukocytosis

Hypercalcemia and leukocytosis are often associated with primary lung cancer as a paraneoplastic syndrome. Recently, parathyroid hormone-related protein (PTHrP) and granulocyte colony stimulating factor (G-CSF) have been identified as major causative peptides for hypercalcemia and leukocytosis, respectively. We studied four men with advanced primary lung cancer (stages from IIIA to IV) who presented with hypercalcemia (corrected serum calcium levels: 10.5 mg/dl) and leukocytosis (WBC > 10,000 per mm3). The age of the patients ranged from 59 to 79 years old. The pathological subtypes were squamous cell carcinoma in three and adenocarcinoma in one. The mean serum calcium levels and leukocyte counts were 15.8 +/- 1.4 mg/dl (mean +/- SE) and 24,800 +/- 3,253 cells/mm3 (mean +/- SE), respectively. Abnormally high serum levels of PTHrP and G-CSF were found in three patients (mean +/- SE: 137 +/- 68 pg/ml; normal range in human serum, < 16 pg/ml), and in all four (mean +/- SE: 72 +/- 7.7 pg/ml; normal range in human serum, < 20 pg/ml), respectively. Immuno-histochemical examination of cancerous tissue obtained from these patients showed positive staining for both PTHrP and G-CSF within the cytoplasm of all the cancerous tissue. These results suggest that the association of hypercalcemia and leukocytosis in patients with advanced primary lung cancer is caused by production of both PTHrP and G-CSF by cancerous tissue.

The Incidence of Corrected Hypercalcemia and Its Relationship with Prognosis for Chinese Multiply Myeloma.

Abstract 4903 PurposeThis paper is to study and analze the serum calcium level after corrected for serum albumin and its effect on prognosis in Chinese multiple myeloma (MM). MethodsSerum calcium levels before and after corrected by serum albumin were retrospectively analyzed in 165 Chinese multiple myeloma patients. Corrected serum calcium (mmol/L)=serum calcium (mmol/L) – 0.025 x serum albumin (g/L)+1.0 (mmol/L). We also analyzed the relationship of serum calcium, serum creatinine and disease categories in Durie-Salmon (DS) staging system with patients' long-term overall survival rate. ResultsIn 165 patients, the incidences of before and after corrected hypercalcemia were 8.7% and 40.6%, which were statistically significantly different (p=0.0245). Based on DS staging, the before and after corrected serum calcium levels of sixteen MM patients in I stage were 2.316±0.082 mmol/L and 2.344±0.073 mmol/L with a p value equal to 0.3236; the before and after correccted serum calcium levels of fifty MM patients in II stage were 2.314±0.17 and 2.407±0.235 mmol/L with a p value equal to 0.0251; the before and after corrected serum calcium levels of ninety-nine MM patients in II stage were 2.428±0.32 and 2.671±0.309 mmol/L with a p value equal to 0.0000. There is no significant difference in overall survival time between normal serum calcium group and elevated serum calcium group, p=0.8929. There is significant difference in overall survival time between normal serum creatinine patients and raised serum calcium patients with a p value equal to 0.0170. Patients in I stage in DS staging system have statistically significant longer overall survival time than those patients in II/III stage in DS staging system, p=0.0382. ConclusionThe incidence of corrected hypercalcemia in Chinese MM is similar to foreign reports. Hypercalcemia has smaller or limit impact on patients' long-term overall survival compared to serum creatinine and DS staging. DisclosuresNo relevant conflicts of interest to declare.

Primary hyperparathyroidism with breast carcinoma

Although hypercalcemia is a common complication of breast carcinoma (BC), it may be due to primary hyperparathyroidism (pHPT), which has a similar sex or age predilection to that of BC. The rate of underlying asymptomatic pHPT in BC patients with hypercalcemia is exceptionally high, so the clinical data were retrospectively analyzed. To investigate coexistent pHPT in BC patients, the medical records of persons who had undergone surgery for primary BC without bone metastases between October 2004 and March 2008 at the Tsuchiura Kyodo General Hospital were retrospectively reviewed. The corrected serum calcium level was measured in all 243 patients. Ten patients who noted hypercalcemia above 11.0mg/dl via the corrected serum calcium were selected in order to investigate pHPT. Among the 243 patients investigated, 7 were diagnosed with pHPT, and 5 of those patients required surgical treatment. In all five patients, the parathyroids were pathologically diagnosed to have adenoma. Primary hyperparathyroidism was diagnosed in 2.88% of the BC patients, which was more than expected, in comparison to the incidence of pHPT in adult women, which is 0.04-0.08%. It is important to assess whether pHPT is associated with the treatment of BC.

The Timing of Calcium Measurements in Helping to Predict Temporary and Permanent Hypocalcaemia in Patients Having Completion and Total Thyroidectomies

Postoperative hypocalaemia commonly occurs after extensive thyroid surgery and may require calcium and/or vitamin D supplements to alleviate or prevent the symptoms. In this study, we determined the risk factors for developing hypocalcaemia and whether early serum calcium levels can predict the development of or differentiate between temporary or permanent hypocalcaemia. A total of 162 patients who either had a completion or total thyroidectomy formed the basis of this prospective study. Serial serum calcium measurements were recorded as well as details of the operation, pathology, indications for surgery, number of parathyroids identified at operation and any complications. Eighty-four (52%) patients did not develop hypocalcaemia but 69 (43%) were found to have temporary hypocalcaemia and 9 (5%) had permanent hypocalcaemia. Hypocalcaemia was more common after total than completion thyroidectomies and the identification of parathyroids at operation appears to have a significant adverse effect on outcome. The calcium levels measured on day 1 postoperatively and the slope (serum calcium levels of day 1 postoperative minus day of operation) were statistically significant in predicting the development of hypocalcaemia and possibly to differentiate between temporary or permanent hypocalcaemia. Although almost half the patients having extensive thyroid surgery developed hypocalcaemia (as defined by any postoperative corrected serum calcium level of < 2.12 mmol/l) only 24% had a serum calcium of < 2.12 mmol/l associated with clinical symptoms of hypocalcaemia or a calcium level of < 2.0 mmol/l. Only 5% had persistent hypocalcaemia defined as requiring exogenous supplements at 6 months' postoperatively. Patients having a completion thyroidectomy appear to be less likely to develop hypocalcaemia perhaps as a result of any iatrogenic effects on the parathyroids at the first operation being reversed before the second operation. Identification and, therefore, exposure of parathyroids at operation may have an adverse effect on the blood supply to the glands affecting their function. Serum calcium levels measured 6 hours' post-surgery and on day 1 postoperatively can be useful in predicting if the patient will develop hypocalcaemia and the slope may indicate whether the hypocalcaemia will be temporary or permanent. Patients with toxic goitres and those having a one-stage total thyroidectomy are most at risk of developing hypocalcaemia.

Multicenter prospective randomized, double-blind comparative study between lanthanum carbonate and calcium carbonate as phosphate binders in Japanese hemodialysis patients with hyperphosphatemia

The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study. The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders. In the double-blind phase, the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group. Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia.

Avaliação da hipercalcemia assintomática em pacientes ambulatoriais

INTRODUCAO: Dosagens indiscriminadas de calcio serico podem levar a deteccao de pacientes assintomaticos, com hipercalcemia, em que o hiperparatireoidismo primario e a causa mais comum. OBJETIVO: Discutir a forma de avaliacao da hipercalcemia detectada em populacao atendida em regime ambulatorial, avaliando a sua frequencia, com enfase na pesquisa de hiperparatireoidismo primario. MATERIAL E METODOS: Foi realizado estudo prospectivo envolvendo 1.049 individuos, de 40 a 60 anos, com dosagens sericas de calcio e albumina, e calculado o valor de calcio corrigido. Na presenca de elevacao do calcio corrigido, foram dosados calcio ionico, fosforo, paratormonio (PTH) e calciuria. RESULTADOS: A idade foi 49,7 ± 13,7 anos e 188 (17,9%) individuos apresentaram valores elevados de calcio corrigido. Desses, 90 pacientes compareceram a segunda avaliacao e 19 (2%) mantiveram quadro de hipercalcemia. Os niveis de calcio ionico (media: 1,2 ± 0,01 mmol/l) foram normais em todos os individuos. A calciuria foi 185,8 ± 111,8 mg/24 horas. Os niveis de PTH (media: 46 ± 11,8 pg/ml) foram elevados em tres casos, com cintilografia de paratireoides normal. DISCUSSAO: A queda na frequencia de hipercalcemia com base no valor do calcio corrigido e, sobretudo, apos dosagem de calcio ionizavel sugere que a dosagem de calcio livre seja preferida como triagem. Na populacao estudada nao foi diagnosticado hiperparatireoidismo, sugerindo distribuicao variavel da doenca em diferentes populacoes. CONCLUSAO: Deve ser questionada a dosagem rotineira de calcio serico em individuos sem quadro clinico que indique a necessidade da realizacao desse exame. Quando realizada, a dosagem de calcio ionico devera ser preferida.

Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma

In a randomized, phase 3 trial, sunitinib demonstrated superior efficacy over interferon-alfa as first-line therapy in patients with metastatic clear-cell renal cell carcinoma (RCC). On the basis of outcome data from that trial, the authors developed a nomogram for predicting the probability of 12-month progression-free survival for patients who received sunitinib therapy. Three-hundred seventy-five patients who received sunitinib in the phase 3 trial were the subject of the current analysis. Nomogram pretreatment predictor variables included corrected serum calcium levels, the number of metastatic sites, hemoglobin levels, prior nephrectomy, the presence of lung and liver metastases, thrombocytosis, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, and serum levels of alkaline phosphatase and lactate dehydrogenase. Investigator-assessed progression-free survival was the predicted outcome endpoint. Internal validation of the nomogram consisted of quantification of the discrimination with the concordance index and assessment of calibration. One-hundred seventy-four of 375 patients (46%) who received sunitinib achieved an objective response, and the median progression-free survival was 10.8 months (95% confidence interval, 10.6-12.6 months). A nomogram for predicting the probability of 12-month progression-free survival for patients who received sunitinib therapy was constructed on the basis of a Cox regression model from 11 parameters that were determined before treatment. The concordance index was 0.633. A nomogram was developed from pretreatment clinical features to predict the probability of achieving 12-month progression-free survival with sunitinib therapy for metastatic clear-cell RCC. The authors concluded that independent validation of the nomogram and additional studies to identify tumor-specific prognostic factors are warranted.

Quantification of gadolinium in nephrogenic systemic fibrosis: Re-examination of a reported cohort with analysis of clinical factors

Nephrogenic systemic fibrosis (NSF) has been associated with exposure to gadolinium-based contrast agent (GdCA) used in medical imaging. We sought to quantify levels of gadolinium in affected skin of patients with NSF and correlate the levels to clinical and laboratory parameters. Skin biopsy specimens were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS) and the micrograms of gadolinium per gram (microg/g) of dry tissue were determined. Clinical and laboratory data were obtained through retrospective chart review. Pearson correlation coefficients were used to correlate tissue gadolinium levels with various parameters. Six patients from a prior cohort were analyzed for gadolinium in affected skin. The mean amount of gadolinium in affected skin of NSF patients was 320.1 microg/g. No gadolinium was found in limited control tissue from patients unexposed to GdCA or in patients exposed to such agents, but without disease. Higher levels of gadolinium in skin correlated with younger age, lower body weight, lower corrected serum calcium levels, and lower erythropoietin dosing. The study was limited by the small number of cases and by the retrospective nature of the data and skin samples. Gadolinium is present in substantial amounts within the skin of patients with NSF. Quantification of gadolinium in tissue using ICP-MS may facilitate our understanding of the disease.

Comparison of Sevelamer Hydrochloride With Colestimide, Administered Alone or in Combination With Calcium Carbonate, in Patients on Hemodialysis

Since hyperphosphatemia in hemodialysis patients can cause secondary hyperparathyroidism and promotes vascular calcification, serum phosphate (Pi) levels must be controlled by phosphate binders. Although sevelamer and colestimide are known as similar non-calcium, non-aluminum phosphate binders in hemodialysis patients, there are no studies that compare the effects of the two agents as either a monotherapy or in combination with calcium carbonate (CaCO3). We randomly allocated 62 hemodialysis patients with hyperphosphatemia to treatment with sevelamer (3.0 g/day) and colestimide (3.0 g/day). During the study, 35 subjects dropped out, leaving 13 in the sevelamer group and 14 in the colestimide group. After a 2-week CaCO3 washout, all subjects received the monotherapy for 4 weeks and then CaCO3 (3.0 g/day) was added for another 4 weeks. Serum corrected calcium levels tended to decrease in both groups during the washout period and monotherapy, but there was no significant difference between the two groups after the addition of CaCO3. Although the calcium x phosphorus product (Ca x P) in the two groups increased during the washout period, there was no significant change or difference between the two groups during monotherapy. However, the addition of CaCO3 significantly reduced serum Pi at Week 8 compared to that at Week 0 in both groups, and significantly lowered Ca x P only in the sevelamer group, but not in the colestimide group(.) In this short-term study, sevelamer and colestimide similarly ameliorated hyperphosphatemia, but the combination of sevelamer and CaCO3 was more effective than colestimide with CaCO3 in controlling the Ca x P product, and it may improve cardiovascular mortality in hemodialysis patients.

Diffuse punctate calcifications involving the colonic region

A 50-year-old gentleman diagnosed as having diabetic nephropathy, with end-stage renal disease (ESRD) one year ago, was advised continuous ambulatory peritoneal dialysis (CAPD) in view of repeated access failure in hemodialysis. His blood urea was 102 mg/dl; serum creatinine, 9.1 mg/dl; corrected serum calcium, 8.7 mg/dl and serum phosphorus level, 7.4 mg/dl. He underwent percutaneous Tenckhoff CAPD catheter insertion. A plain X-ray of the abdomen (erect) was obtained to confirm the position of the catheter [Fig. 1]. Fig. 1 Plain X-ray abdomen (erect) of the patient The X-ray showed diffuse punctate calcifications in the region of the colon along with the CAPD catheter in-situ. Calcifications observed in flat plate films of the abdomen can be broadly divided into two types: those that are confined to a particular organ and those diffusely occupying the whole abdomen. In our patient, the distribution was more suggestive of punctate discrete calcifications in the region of the large intestine. He was on lanthanum carbonate 500 mg thrice a day for his hyperphosphatemia. Recently, reports of incidentally discovered calcific shadows in the colonic region amongst patients on Lanthanum carbonate have been published.1,2 Lanthanum is a rare earth metal bearing atomic number 57, which is close to that of Barium (56). This phenomenon is important since misdiagnosis and endoscopic procedures can be avoided. This method can also be used to assess drug compliance.2

Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study

Abstract. Incadronate has been found to lessen the increase in corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a Phase III study in Japan. The drug is currently used to treat MAH in Japan. The purpose of this study was to assess the clinical usefulness of incadronate in patients with MAH. This open-label study was conducted at 3 medical institutions in Korea. Korean patients with MAH (corrected serum calcium levels ≥11.0 mg/dL) were given a single 10-mg IV infusion of incadronate over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels were determined and subjective symptoms and objective findings (ie, bone pain, spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite, nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of consciousness) were used to monitor the effectiveness of the drug for 6 days after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3 = severe). Adverse events (AEs) were identified by patients' reports, and adverse drug events (ADEs) were assessed by the investigators throughout the study. Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5 years) were included in the study; data from 22 and 24 patients were used to assess effectiveness and tolerability, respectively. Corrected serum calcium level was significantly decreased on day 6 after treatment compared with pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P < 0.001). The antihypercalcemic effect of incadronate became apparent as an inhibition of bone absorption a few days after infusion. Corrected serum calcium level was significantly decreased on days 2 to 6 (P < 0.001) after treatment compared with pretreatment at baseline. Evaluation of symptoms showed significant improvement in the incadronate-treated group (mean total score [range] at baseline, 8 [1-23] and day 6, 5.5 [1-17]; P = 0.001). Eight (33.3%) of the patients were found to have ADEs. Some of the 8 patients experienced >1 ADE (mild and transient fever [13 events], chills [3], headache [1], and myalgia [1]). AEs were observed in 19 (79.2%) of 24 patients. The most frequently reported AE was fever (14 events). In this small, open-label study, Korean subjects with MAH treated with incadronate experienced significant improvement in symptoms and calcium levels from baseline.

Elderly patient presenting with severe thyrotoxic hypercalcemia

An 81‐year‐old woman with Graves’ disease and osteoporosis was referred to the hospital because of anorexia over one month and impaired consciousness. She also presented with low‐grade fever and emaciation. Laboratory tests revealed marked hypercalcemia (corrected serum calcium level of 12.4 mg/dL), which was initially suspected to result from vitamin D toxicity, because she had been taking vitamin D3 (alphacalcidol of 0.5 µg/day) for the treatment of osteoporosis. However, discontinuation of vitamin D3 and fluid infusion did not ameliorate hypercalcemia one week later. After excluding hyperparathyroidism and malignancy‐related hypercalcemia, hypercalcemia was considered to be attributable to the exacerbation of hyperthyroidism (free T4 of 6.69 ng/dL, free T3 of 13.27 pg/mL and thyroid stimulating hormone (TSH) &lt;0.015 µIU/mL) with increased bone resorption. Finally, the increased dose of thiamazole (30 mg/day) normalized serum calcium level and thyroid function three months later. Laboratory tests suggested that normal bone formation in spite of increased bone resorption contributed to hypercalcemia in hyperthyroid state.

Carotid artery plaque thickness is associated with increased serum calcium levels: The Northern Manhattan study

Background Elevated serum calcium concentrations are associated with vascular calcification and cardiovascular disease. It is unknown whether there is a relationship between high-normal serum calcium levels and sub-clinical vascular effects. We investigated the association between serum calcium and carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events. Methods Epidemiological study of 1194 subjects from the Northern Manhattan Study cohort, a prospective community-based study designed to investigate risk factors for vascular disease in different race-ethnic groups. Results Subjects with carotid plaque had higher corrected serum calcium levels within the normal range than those without carotid plaque (2.21 ± 0.09 mmol/L versus 2.19 ± 0.09 mmol/L, p < 0.002). The relationship between carotid plaque and serum calcium persisted after adjustment for traditional cardiovascular risk factors. Subjects in the top quintile of maximal carotid plaque thickness (≥1.7 mm) were more likely to be in the highest quintile of serum calcium level (OR = 1.64, 95% CI = 1.17–2.29, p < 0.004). The interaction of age and corrected serum calcium was the most significant predictor of carotid plaque thickness when traditional vascular risk factors were considered ( p < 0.001). Conclusions Serum calcium levels in a multi-ethnic population of older men and women were positively associated with carotid plaque thickness, a powerful early predictor of clinical coronary and cerebrovascular events.