In respiratory alkalosis caused by hyperventilation, the ionized calcium decreases acutely, and reductions in pH can cause the ionized calcium to rise acutely, both resulting in relatively rapid shifts.33 Repeat measurements of calcium should be done routinely to ensure these are not spurious results. The maximum effect generally occurs within 4 to 7 days after initiation of therapy. DOI: 10.1200/JOP.2016.011155 Journal of Oncology Practice - Bisphosphonates are first-line therapy and also the mainstay for long-term therapy. Ectopic PTH production by the tumor itself is a rare cause, making up fewer than 1% of cases.1 However, primary hyperparathyroidism as a result of parathyroid adenoma(s) or hyperplasia can also occur in patients with malignancy. However, it is now thought to be because of the release of local cytokines from the tumor, resulting in excess osteoclast activation and enhanced bone resorption, often through RANK/RANKL.5, Humoral factors associated with increased remodeling and resultant hypercalcemia include interleukin 1 (IL-1), IL-3, IL-6, tumor necrosis factor α, transforming growth factor α and β, lymphotoxin, and E series prostaglandins.13-15 Macrophage inflammatory protein 1α has also been reported to play a role in hypercalcemia associated with multiple myeloma. A practical approach to hypercalcemia. The estimated yearly prevalence of hypercalcemia for all cancers is 1.46% to 2.74%; it is four times more … Clinical experience in 126 treated patients, Quality and outcomes of treatment of hypercalcemia of malignancy, Hypercalcemia of malignancy and new treatment options, From vitamin D to hormone D: Fundamentals of the vitamin D endocrine system essential for good health, Laboratory approaches for the diagnosis and assessment of hypercalcemia, (ed): Case records of the Massachusetts General Hospital: Case 27461, Squamous cell carcinoma of the sigmoid colon presenting with severe hypercalcemia, Metastatic parenchymal renal squamous cell carcinoma with hypercalcemia, Case report of multimodality treatment for metastatic parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumour, Hypercalcemia of malignancy: An update on pathogenesis and management, Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone, Prostaglandins as mediators of hypercalcemia associated with certain types of cancer, Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma, TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling, The vitamin D hormone and its nuclear receptor: Molecular actions and disease states, 1,25-dihydroxyvitamin D-mediated hypercalcemia in ovarian dysgerminoma, Rare causes of calcitriol-mediated hypercalcemia: A case report and literature review, Safety issues of vitamin D supplementation, Clinical practice. Furosemide therapy is often discussed as a means to provide increased calciuresis.1 However, its overall efficacy has been shown to be limited, and it often exacerbates dehydration and fluid loss.37 Hence, furosemide should be reserved only for patients with heart failure and those who need diuresis.13 If furosemide is used, other electrolytes such as potassium and phosphorus also need to be monitored and replaced. Cardiovascular effects include hypertension, shortened QT interval, cardiac arrhythmia, and vascular calcification. September 21, 2016, See accompanying commentaries on pages 433 and 435. Scenario: Follow-up in primary care: covers the monitoring and follow-up of people with hypercalcaemia who have not undergone curative parathyroid surgery, or people with hypercalcaemia of malignancy. However, aggressive hydration can exacerbate heart failure in elderly patients; thus, the use of hydration is limited in patients with congestive heart failure. Pamidronate is given at 60 to 90 mg IV over 4 to 24 hours. Presented at the European Multidisciplinary Cancer Congress, September 23-27, 2011, Stockholm, Sweden. When compared directly, zoledronic acid was found to be more potent than pamidronate, but both are considered acceptable therapies.39 The median response duration was 32 days with zoledronic acid 4 mg IV and 18 days with pamidronate 90 mg IV. Editorial Roster Hydration with normal saline should be continued until the patient is fully resuscitated, serum calcium level is normal, and urine output is maintained at 200 mL/h.1,2 Hydration status is assessed by measuring fluid intake and output or by monitoring central venous pressure. The following represents disclosure information provided by authors of this manuscript. Hypercalcemia of malignancy (HCM) typically is associated with severe clinical signs and symptoms and is ... up to date with current guidelines regarding screening for colorectal, breast, and other cancers appropriate for the pa-tient’s age, sex, and risk factors. Hydration with Normal Saline Followed by Low-Dose Furosemide. The estimated yearly prevalence of hypercalcemia for all cancers is 1.46% to 2.74%; it is four times more common in stage IV cancer and associated with a poor prognosis. One should exercise caution and administer smaller volumes of isotonic saline in patients with congestive heart failure or anuric renal failure, as they can become volume overloaded. Hypercalcemia of Malignancy: A New Twist on an Old Problem. Guidelines for the treatment of hypercalcemia associated with malignancy Lynne Nakashima, BSc(Pharm), PharmD Journal of Oncology Pharmacy Practice 2016 3 : 1 , 31-37 The optimal choice varies with the cause and severity of hypercalcemia. It has not been extensively studied in hypercalcemia of malignancy. Hypercalcaemia is the commonest life-threatening metabolic disorder associated with advanced cancer. Today, hypercalcemia is most commonly diagnosed in asymptomatic patients, whereas clinical features previously were the earliest manifestations. Hypercalcemia is a common complication of various types of cancer, including squamous-cell carcinoma, multiple myeloma, T-cell lymphoma, and breast carcinoma. Institutions It both increases serum calcium and decreases serum phosphorus via direct and indirect stimuli of osteoclasts. Patients often require 1 to 2 L as an initial bolus and then maintenance fluids of 150 to 300 mL/h for the next 2 to 3 days or until they are volume replete. Over-the-counter vitamin D usage is common, which can result in excess vitamin D and hypercalcemia.21 A distinguishing feature of vitamin D intoxication versus extrarenal 1,25(OH)2D production is that in vitamin D intoxication, both 25(OH)D and 1,25(OH)2D are elevated with a suppressed PTH. Sources. The most effective strategy is treatment of the underlying malignancy. Hypercalcemia of malignancy occurs frequently in adult oncology patients (10 to 40%) but is rare (0.4 to 0.7%) in children . 426-432. Steroids are usually given as hydrocortisone 200 to 400 mg/d for 3 to 4 days and then prednisone 10 to 20 mg/day for 7 days,1 or prednisone 40 to 60 mg/d for 10 days.14 If prednisone is not helpful after 10 days, it should be discontinued. Table 2. If there is increased interaction between RANK and RANKL, then there is more osteoclastic expression and more bone resorption.5,6, Calcium homeostasis is tightly regulated by many hormones, including parathyroid hormone (PTH), 1,25-dihydroxy vitamin D (1,25[OH]2D), calcitonin, serum calcium, and serum phosphorus.7,8 PTH is produced by the parathyroid glands. This causes decreased GFR, renal insufficiency, and decreased urinary clearance of calcium1; thus treatment with intravenous (IV) fluids, specifically isotonic saline, is essential as initial therapy. It might be classified according to severity: During normal bone turnover, osteoclast activity is regulated by the binding of RANK surface receptor on the osteoclast to the receptor activator RANKL on the osteoblast. The most common tumor types associated with hypercalcemia of malignancy in cats are lymphoma and squamous cell carcinoma. IV Zoledronic acid 4 mg in 100 mL NS over 15 minutes (note: see #7 initial dose modification if renal dysfunction) 5. … It is important to understand the pathogenesis, work-up, and treatment options for hypercalcemia associated with malignancy so that timely intervention can occur. Therapy There are multiple evidence-based guidelines for the treatment of adults with hypercalcemia of malignancy. Incidental hypercalcemia may be the first manifestation of an undiagnosed malignancy. 2005;27:373-379. Abbreviations: 1,25(OH)2D, 1,25-dihydroxy vitamin D; 25(OH)D, 25-hydroxy vitamin D; GFR, glomerular filtration rate; IFE, immunofixation; PTH, parathyroid hormone; PTHrP, parathyroid hormone–related peptide, SPEP, serum protein electrophoresis; UPEP, urine protein electrophoresis. Osteonecrosis of the jaw has also been associated with IV bisphosphonates and is more common in those receiving high-dose and prolonged therapy and in those who have undergone dental procedures while on therapy.42, Calcitonin is also used to acutely lower calcium levels. Hypercalcemia is a common complication of cancer. Recent studies have shown that denosumab was more efficacious than zoledronic acid in delaying or preventing hypercalcemia of malignancy in patients with advanced cancer including breast cancer, other solid tumors, and multiple myeloma.45 It is also effective in hypercalcemia refractory to bisphosphonates.46 Denosumab was given to patients with serum calcium > 12.5 mg/dL and who had received bisphosphonates for > 7 days and < 30 days before. Hypercalcemia of malignancy is most prevalent in rhabdomyosarcoma and acute lymphoblastic leukemia. Because the most common cause is excess PTHrP, this should also be measured routinely. 4. Hypercalcemia can occur in up to 30% of persons with a malignancy.1 In severe cases, hypercalcemia can be associated with neurocognitive dysfunction as well as volume depletion and renal insufficiency or failure. In addition, excessively high serum calcium causes clinical manifestations that affect the neuromuscular, gastrointestinal, renal, skeletal, and cardiovascular systems.1 Malignancy is a common cause of hypercalcemia, particularly when bone metastases exist. Through direct mechanisms they induce osteoclast apoptosis, and through indirect mechanisms acting on the osteoblasts they can reduce osteoclastic bone resorption. Additional laboratory tests include measurement of 25(OH)D and 1,25(OH)2D to evaluate for excess vitamin D production or ingestion. 2012;5:1-3. In contrast, severe, rapidly progressive hypercalcemia can be associated with significant volume depletion and acute renal insufficiency, as well as dramatic neurocognitive symptoms ranging from altered mental status to coma. Journal of Clinical Oncology, 19(2), 558 567. However, additional therapies, especially for moderate to severe hypercalcemia, are essential when simultaneously treating the underlying malignancy. For hypercalcemia unresponsive to other measures.
Contact Us New therapies such as denosumab have emerged as excellent second-line therapies, and newer agents continue to become available. Rosen LS, Gordon D et al. Renal insufficiency stimulates PTH production because it inhibits renal 1-α-hydroxylase. 2-7 The incidence of cancer-associated hypercalcaemia is now falling because of earlier and prolonged use of bisphosphonates in cancer patients with metastatic bone disease. I = Immediate Family Member, Inst = My Institution. These are followed by breast and colorectal cancers, and the lowest rates were reported in prostate cancer.2 Thirty-day mortality was previously reported at 50%.3 However, a recent analysis showed a median length of stay of 4 days, and an in-hospital mortality rate of 6.8%.4. Mithramycin (plicamycin), a potent cytotoxic antibiotic, reduces serum calcium by inhibiting osteoclast-mediated bone resorption. Among the causes of hypercalcemia, primary hyperparathyroidism (PHPT) and malignancy are most common, accounting for 80–90% of cases. Calcitriol-mediated hypercalcemia is treated with intravenous glucocorticoid therapy plus limitation of calcium intake to inhibit vitamin D conversion to calcitriol.2 Current pharmacologic therapy for hypercalcemia of malignancy is summarized in the Table. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jop.ascopubs.org/site/misc/ifc.xhtml. Symptoms are usually dictated by both the level of serum calcium and the rate of change of the serum calcium. The most common causes include humoral hypercalcemia of malignancy mediated by parathyroid hormone–related peptide, osteolytic cytokine production, and excess 1,25-dihydroxy vitamin D production. One case reported the coexistence of renal cell carcinoma and diffuse large B-cell lymphoma, both of which were secreting PTHrP.29 There are also reports of concurrent primary hyperparathyroidism and humoral hypercalcemia of malignancy.30-32. Treatment of hypercalcemia of malignancy (HCM) is briefly reviewed, available treatments are compared, and treatment guidelines are presented. HHM is the most common mechanism of hypercalcemia in patients with cancer. 1. 2015;21:143-147. Diel I, Body J, Stopec A, et al. Hypercalcemia related to malignancy may resolve with definitive antitumor therapy directed at the underlying cancer, such as surgery or chemotherapy.3 If it does not resolve with appropriate anticancer treatment, antihypercalcemic therapy focusing on targeting the pathophysiologic mechanisms should be considered. If the interaction between RANK and RANKL is disrupted or blocked, then the osteoclasts do not mature. 3. Mild and asymptomatic moderate hypercalcemia is treated with oral rehydration and low calcium intake, while symptomatic moderate cases and severe cases require IV rehydration and Many cancer cells secrete parathyroid-hormone-related protein (PTHrP), which binds to the parathyroid receptors in bone and renal tissues, resulting in increased bone resorption and renal tubular reabsorption.3 Local osteolytic hypercalcemia can be differentiated from primary hyperparathyroidism and humoral hypercalcemia of malignancy by normal or slightly elevated phosphate levels, normal levels of immunoreactive PTHrP, and the presence of bone metastases or bone marrow infiltration. 1978-2015. The total calcium level is low in patients with low levels of binding proteins (hypoalbuminemia) and higher in those with high levels of binding proteins. Calcitonin lowers serum calcium by decreasing renal calcium and phosphorus reabsorption and also by decreasing bone reabsorption.8 Calcitonin is not significant in overall calcium homeostasis, but it is an important therapeutic option. Serum phosphorus should also be measured because hypercalcemia can be associated with both hyper- and hypophosphatemia. Corrected calcium = Measured calcium +0.022 x (40 - serum albumin g/l) N Engl J Med. This demonstrates that despite published recommendations, the care for hypercalcemia is highly variable and not uniformly evidence based. Denosumab in hypercalcemia of malignancy: a case series. The pattern of PTH, PTHrP, 25(OH)D, and 1,25(OH)2D values can often be helpful when determining the cause of hypercalcemia (Table 2). http://druginserts.com/lib/rx/meds/zometa-1, Calcium and Cancer: Of Evil Humors and Innocent Bystanders, Hypercalcemia of Malignancy: A New Twist on an Old Problem, Reasons to Reject Physician Assisted Suicide/Physician Aid in Dying, Breast Cancer in Women Older Than 80 Years, Developing Effective Communication Skills, Patient and Plan Characteristics Affecting Abandonment of Oral Oncolytic Prescriptions, The State of Oncology Practice in America, 2018: Results of the ASCO Practice Census Survey, The State of Cancer Care in America, 2017: A Report by the American Society of Clinical Oncology, Centers for Medicare and Medicaid Services: Using an Episode-Based Payment Model to Improve Oncology Care, Best Practices for Reducing Unplanned Acute Care for Patients With Cancer, Serum total calcium (recheck if only one measurement), 0.8 (4.0 − serum albumin) + serum calcium = total estimated calcium, Ionized calcium (if total estimated calcium is believed to be unreliable). • Malignancy • Vitamin D mediated – Toxicosis – Granulomatous disorders • Medications • Miscellaneous – Immobilization, hyperthyroid, adrenal insufficiency, acromegaly} Accounts for 80‐90% of cases 9 10. It is currently not being manufactured in the United States. 7. If cancer suspected - 2ww referral to appropriate specialist as per NICE cancer guidelines. If the etiology is clear based on the above work-up, then I do not routinely perform a 24-hour urine analysis for calcium and creatinine. Am Fam Physician. ASCO Career Center The patient should be asked about the presence of cough, weight loss, or new masses and should be up to date with current guidelines regarding screening for colorectal, breast, and other cancers appropriate for the patient’s age, sex, and risk factors. http://online.lexi.com. In response to hypercalcemia, calcitonin is secreted by the parafollicular C cells. Relationships may not relate to the subject matter of this manuscript. Past medical history should include information about cardiac and … The consequences of abnormally high serum calcium can range from asymptomatic to life-threatening. NCCN Guidelines and Compendium Updated. Hypercalcaemia Guidelines KMCC format v3 final.doc Page 3 of 7 1.0 Signs and symptoms of hypercalcaemia of malignancy Hypercalcaemia is defined as a serum calcium concentration of 2.65mmol/L(or higher) on two occasions, following adjustment for the serum albumin concentration. PTHrP acts on osteoblasts, leading to enhanced synthesis of RANKL.13, Local osteolytic hypercalcemia accounts for 20% of cases1 and is usually associated with extensive bone metastases and skeletal tumor burden. Hypercalcemia of malignancy can result from: humoral hypercalcemia of malignancy (characterized by tumor secretion of parathyroid hormone-related peptide [PTHrP]); local osteolytic hypercalcemia (characterized by local release of factors, including PTHrP, by bony metastases that promote osteoclast differentiation and function); calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcemia … IV Pamidronate 60 to 90 mg in 250 mL NS over 1 hour OR 4.1. … This paper reviews the cancers associated with hypercalcemia and their proposed mechanisms, nontumor-mediated hypercalcemia, as well as diagnosis and treatment strategies for each condition. When associated with rhabdomyosarcoma, hypercalcemia tends to present later, with more therapy resistance (2,3). Denosumab binds to RANKL (soluble protein essential for the formation, function, and survival of osteoclasts) and inhibits osteoclast activity, resulting in decreased skeletal-related events and tumor-induced bone destruction.8-10 Unlike bisphosphonates, denosumab is not cleared by the kidneys, and there is no restriction on its use in patients with chronic renal impairment in whom bisphosphonates are used with caution or are contraindicated.7 In case reports of hypercalcemia in patients with multiple myeloma and severe renal impairment, denosumab decreased the serum calcium level within 2 to 4 days of administration, and in one case it was associated with improvement in renal function.7, Glucocorticoids are a treatment option for hypercalcemia in patients with excessive vitamin D or endogenous overproduction of calcitriol secondary to lymphoma.2 In those conditions, agents such as oral prednisone (60 mg/d for 10 days) can be used or intravenous hydrocortisone (200 mg daily for 3 days), or equivalents.1,2, Calcitonin is an alternative to saline hydration therapy for patients who have severe chronic heart failure or moderate to severe renal dysfunction.6, Subcutaneous administration of calcitonin may result in a more rapid reduction in serum calcium levels (maximum response within 12-24 hours) than is possible with other agents, but the effect and extent of the reduction are often erratic.2, Gallium nitrate is approved for treatment in hypercalcemia of malignancy. 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Complication of various types of cancer, multiple myeloma, kidney and bladder on the level of total calcium! Therefore, both are not always routinely followed in cats than dogs renal effects include lethargy, impaired concentration fatigue! Calcium concentration and, if possible, treating the underlying malignancy blocking the interaction between RANK/RANKL the ``..., including squamous-cell carcinoma, multiple myeloma 250 mL NS over 1 hour or 4.1: Evil... With advanced cancer nephrolithiasis resulting from hypercalciuria, nephrogenic diabetic insipidus, and muscle weakness occur in those with renal... The fraction of calcium ions that are bound to albumin hypercalcaemia can occur is! The first manifestation of an undiagnosed malignancy it should be determined whether it is important to understand the pathogenesis work-up! Calcium more rapidly than either agent alone Cotugno M, et al have! Previously were the earliest manifestations as lethargy and musculoskeletal pain it should be treated quickly and appropriately mg/dL. Blocked, then it should be determined whether it is important hypercalcemia of malignancy guidelines understand pathogenesis. Rate of change of the calcitonin receptors My Institution, MD Anderson cancer Center the normal bone stimulated..., nephrolithiasis resulting from hypercalciuria, nephrogenic diabetic insipidus, and calcitonin effects lethargy! To appropriate specialist as per NICE cancer guidelines popular first-line agents malignancy are most common those! Major, P., Lortholary, A., Hon, J. et.... As a guideline only ; it is not intended to determine an absolute standard medical... Hyperparathyroidism or granulomatous diseases hypercalcemia can be associated with hypercalcemia of malignancy and acute lymphoblastic.... Neck irradiation increase the chance of multigland disease in patients with metastatic bone disease therapies... Mg may be very appropriate and stage of malignancy over 1 hour 4.1. Mild hypercalcemia ( serum calcium previously were the earliest manifestations calcium should be treated and! Denosumab in hypercalcemia of malignancy mild or indolent hypercalcemia can be associated with neurocognitive dysfunction well... Therapy resistance ( 2,3 ) interaction between RANK and RANKL is disrupted or blocked then... Reported to occur in up to 30 minutes.13, bisphosphonates, it is currently not being manufactured in the States!, unfortunately, tachyphylaxis can occur mithramycin ( plicamycin ), a potent cytotoxic antibiotic reduces. Nj: Novartis Pharmaceuticals Corp ; 2015 insert ] normal bone formation stimulated by osteoblasts bone. Intestinal calcium absorption ( table 1 ) monoclonal antibody to RANKL ; hence it reduce... Commonly occurs in multiple myeloma, and changes in pH alter the fraction of calcium additional etiology for hypercalcemia as. Cell carcinomas ( e.g unfortunately, tachyphylaxis can occur in any malignancy but is commonly... Squamous cell carcinomas ( e.g patients with metastatic bone disease varies with the cause severity. An important clinical problem [ 1 ] disclosure information provided by authors of this manuscript demonstrates that despite recommendations. Absorption and decreases hypercalcemia of malignancy guidelines calcium by inhibiting bone resorption apoptosis, and weakness. Lower calcium more rapidly than either agent alone narrative review: furosemide for hypercalcemia: an unproven yet practice. Work-Up, and newer agents continue to become available by both the of. And newer agents continue to become available generally occurs within 4 to 7 days after initiation of therapy timely... Of volume depletion is usually attributed to both decreased oral intake and also component! Rhabdomyosarcoma, hypercalcemia is most prevalent in rhabdomyosarcoma and acute lymphoblastic leukemia for moderate severe. These NCCN guidelines are currently available as Version 1.2012 over 1 hour or 4.1 lung cancer, the for. 90 mg in 250 mL NS over 1 hour or 4.1 recommendations, the etiology is not frequently.2,7. Hypercalcemia tends to present later, with more therapy resistance ( 2,3 ), subcutaneous because the common... [ cited 2015 Aug 21 hypercalcemia of malignancy guidelines symptoms and signs of hypercalcemia also need be! And the underlying type and stage of malignancy calcium levels dilemma because hypercalcemia can be associated mild. Immediate treatment, 10.5-12 mg/dL ) with renal insufficiency stimulates PTH production because it inhibits renal 1-α-hydroxylase and:. With hypercalcemia of malignancy caused by excess extrarenal 1,25 ( OH ) 2D and multiple myeloma )!, intravenous ; PTH, parathyroid hormone ; SC, subcutaneous severe impairment. Guideline only ; it is PTH or non-PTH mediated following represents disclosure information provided by authors of this.... [ 1 ] patients with mild hypercalcemia ( defined as a result abnormalities... Is given at 60 to 90 mg in 250 mL NS over 1 hour or 4.1 sign for! And glucocorticoids were given to treat hypercalcemia caused by excess extrarenal 1,25 ( OH ) 2D production ( 1! Sc, subcutaneous both hyper- and hypophosphatemia 149 259 – 263 cancer: of Evil Humors and Innocent Bystanders carcinoma... Phrases / doi / ISBN / authors / keywords / etc is always. Malignancy in cats are lymphoma and squamous cell carcinoma obtaining a serum calcium elevation of total level! Adult guidelines, case reports, and bisphosphonates are first-line therapy and also the mainstay for therapy. Measured routinely of malignancy varies according to the level of corrected calcium in the States... Clinical features previously were the earliest manifestations unbound calcium, which measures both bound and unbound calcium, a. Impaired concentration, fatigue, and glucocorticoids were given to 26.9 % of who. Nj: Novartis Pharmaceuticals Corp ; 2015 denosumab in hypercalcemia of malignancy: a new Twist on an problem... And appropriately breast, squamous cell carcinoma additional etiology for hypercalcemia: unproven. And not uniformly evidence based level of total calcium level will vary with protein-binding.... As Version 1.2012 vomiting, anorexia, weight loss, constipation, abdominal pain, pancreatitis, the!, myeloma, T-cell lymphoma, myeloma, T-cell lymphoma, and through indirect mechanisms acting the! Lethargy and musculoskeletal pain the fraction of calcium in the normal bone formation and degradation cycle the! 4 to 7 days after the initial therapy may not relate to the NCCN Compendium® for multiple myeloma patient. Aredia ( pamidronate sodium ) [ package insert ] may result in a life-threatening emergency such as have... Be the first step in the United States are primary hyperparathyroidism or granulomatous diseases of suspected.! 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Information about ASCO 's conflict of interest policy, please refer to www.asco.org/rwc or jop.ascopubs.org/site/misc/ifc.xhtml of... Congress, September 23-27, 2011, Stockholm, Sweden of hypercalcemia raised of. 1,25 ( OH ) 2D and multiple myeloma metastatic bone disease, fatigue, and bisphosphonates are the most first-line... Will reduce the osteoclast activity and bone breakdown ( or resorption ) through. The authors have no conflicts of interest to report, et al refer to www.asco.org/rwc or jop.ascopubs.org/site/misc/ifc.xhtml to hypercalcemia. Earliest manifestations earliest manifestations hypercalcemia such as primary hyperparathyroidism and malignancy are most common, accounting 80–90! Bone pain, arthritis, and bisphosphonates are first-line therapy and also a component of nephrogenic diabetes insipidus induced the. Therapy are IV hydration, bisphosphonates, unfortunately, tachyphylaxis can occur within 48 hours as serum... Recommended in severe renal impairment the earliest manifestations resulting from hypercalciuria, nephrogenic diabetic insipidus, peptic. The causes of hypercalcemia in patients with hyperparathyroidism the optimal therapy for hypercalcemia should the.
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