An additional consideration is vitamin D intoxication. published online before print Hypercalcemia of malignancy is most prevalent in rhabdomyosarcoma and acute lymphoblastic leukemia. Renal insufficiency stimulates PTH production because it inhibits renal 1-α-hydroxylase. Normal ionized calcium levels are 4 to 5.6 mg per dL (1 to 1.4 mmol per L). The maximum effect generally occurs within 4 to 7 days after initiation of therapy. Enter words / phrases / DOI / ISBN / authors / keywords / etc. It has not been extensively studied in hypercalcemia of malignancy. Fluid replacement, however, is first-line therapy for those with acute renal insufficiency as a result of volume depletion. 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. The zoledronic acid package insert recommends that in hypercalcemia of malignancy, patients with mild to moderate renal impairment before initiation of therapy (serum creatinine < 4.5 mg) do not need dose adjustment. The original guideline is available at: Walsh J, Gittoes N, Selby P, the Society for Endocrinology Clinical Committee. Rosen LS, Gordon D et al. 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. Thus, understanding its mechanism of action is important. If the etiology is not clear with the above laboratory tests, and the diagnosis of multiple myeloma is in question, then serum and urine protein electrophoresis or immunofixation along with a skeletal survey is indicated. All rights reserved.1249 South River Road - Suite 202, Cranbury, NJ 08512. Conquer Cancer Foundation It might be classified according to severity: Two bisphosphonate agents were approved by the US Food and Drug Administration for the treatment of hypercalcemia of malignancy: pamidronate (Aredia) and zoledronic acid (Zometa). In cats, idiopathic hypercalcemia appears to be the most frequent cause of a high total calcium concentration, followed by renal failure and malignancy. Hudson, OH: Wolters Kluwer Health. Rehydration can be accomplished by intravenous administration of normal saline, at a rate of 200 to 500 mL/h or 2 to 4 L/d, depending on renal function, the baseline status of dehydration, and the severity of hypercalcemia. Reviewers 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. 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. PHPT is the major cause of hypercalcemia in the ambulatory population, comprising up to 60% of cases, while malignancy represents the leading cause in hospit… The treatment of hypercalcemia will be reviewed here, with emphasis on the management of hypercalcemia … Hypercalcemia of malignancy: current & future directions. If the serum calcium is believed to be inaccurate, then ionized calcium can be used, but this also has its limitations and can be inaccurate. It occurs primarily in those with more advanced disease and is generally indicative of a poor prognosis. Because of the requirement for continuous intravenous infusion, gallium nitrate is not used frequently.2,7. Hypercalcaemia is defined as a serum calcium concentration of 2.6 mmol/L or higher, on two occasions, following adjustment (correction) for the serum albumin concentration. IV Zoledronic acid 4 mg in 100 mL NS over 15 minutes (note: see #7 initial dose modification if renal dysfunction) 5. Carroll MF, Schade DS. In approximately 60% to 90% of patients, the serum calcium level normalizes within 4 to 7 days, and the response lasts for 1 to 3 weeks.2, Bisphosphonates inhibit bone resorption and decrease bone mineralization by disrupting osteoclast activity.2 The most common adverse reactions are renal toxicity, flulike symptoms, injection site reactions, hypocalcemia, hypophosphatemia, fatigue, muscle weakness, and constipation or diarrhea.4,5 Daily oral supplementation with 500 mg of calcium and a multiple vitamin containing 400 IU of vitamin D is recommended to prevent hypocalcemia.4,5, Denosumab (Prolia), a full human immunoglobulin G2 monoclonal antibody against RANKL, can be used to manage malignancy-associated hypercalcemia in patients with persistent hypercalcemia despite bisphosphonate treatment. Department of Endocrine Neoplasia and Hormonal Disorders Newsletter. JCO Precision Oncology, ASCO Educational Book Institutions Lexicomp. with malignancy, occurring in approximately 10-20% of patients with cancer. Individual risk of hypercalcemia depends on the underlying type and stage of malignancy. Abstract 3051. The University of Texas, MD Anderson Cancer Center. Guidelines for the treatment of hypercalcemia associated with malignancy Lynne Nakashima, BSc(Pharm), PharmD Journal of Oncology Pharmacy Practice 2016 3 : 1 , 31-37 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. Title of Guideline: Management of Hypercalcaemia of Malignancy Date of Submission: November 2015 Date of Review: November 2017 ... Hypercalcaemia of Malignancy: a Pooled Analysis of Two Randomizes, Controlled Clinical Trials. This demonstrates that despite published recommendations, the care for hypercalcemia is highly variable and not uniformly evidence based. Furosemide blocks calcium reabsorption in the loop of Henle and increases urine output, which may necessitate increased saline administration, inducing further renal excretion of calcium.1, Two bisphosphonate agents were approved by the US Food and Drug Administration for the treatment of hypercalcemia of malignancy: pamidronate (Aredia) and zoledronic acid (Zometa).2-5 Bisphosphonate therapy should be initiated as soon as hypercalcemia is detected, because it takes 2 to 4 days to lower the calcium level. One recommendation is for 60 mg subcutaneously once or for a single weight-based dose of 0.3 mg/kg followed by redosing in 1 week if the patient is persistently hypercalcemic.48, Cinacalcet reduces PTH production and is approved for use in secondary hyperparathyroidism and refractory parathyroid carcinoma. 9. Flash Update Sent July 29, 2011. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015. Breast radiation correlates with side of parathyroid adenoma, Lithium-associated hyperparathyroidism: Report of four cases and review of the literature, Hereditary hyperparathyroidism—A consensus report of the European Society of Endocrine Surgeons (ESES), Parathyroid carcinoma, a rare cause of primary hyperparathyroidism, The coexistence of renal cell carcinoma and diffuse large B-cell lymphoma with hypercalcemic crisis as the initial presentation, Concurrent primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell endometrial cancer, Concurrent primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with multiple endocrine neoplasia type 1, Association of primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell renal carcinoma, Letter to the editor: Distinguishing typical primary hyperparathyroidism from familial hypocalciuric hypercalcemia by using an index of urinary calcium, Diagnosis of asymptomatic primary hyperparathyroidism: Proceedings of the Fourth International Workshop, A review in the treatment of oncologic emergencies, Narrative review: Furosemide for hypercalcemia: An unproven yet common practice, Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts, Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: A pooled analysis of two randomized, controlled clinical trials, Effect of intravenous hydration in patients receiving bisphosphonate therapy, Osteonecrosis of the jaw (ONJ): Diagnosis and management in 2015, Regulation of calcitonin receptor by glucocorticoid in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor, Treatment of bisphosphonate-resistant hypercalcemia of malignancy with calcitonin, The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer patients with metastatic bone disease, PTHrP-induced refractory malignant hypercalcemia in a patient with chronic lymphocytic leukemia responding to denosumab, Denosumab for treatment of hypercalcemia of malignancy, Denosumab for the management of hypercalcemia of malignancy in patients with multiple myeloma and renal dysfunction, Renal replacement therapy as a treatment for severe refractory hypercalcemia, Professional English and Academic Editing Support. (2003) Long-term Efficacy and Safety of Zoledronic Acid Compared with Pamidronate Disodium … 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. About Past medical history should include information about cardiac and renal function and previous or current malignancies. Renal effects include dehydration, polyuria, nephrolithiasis resulting from hypercalciuria, nephrogenic diabetic insipidus, and nephrocalcinosis. Hypercalcaemia can occur in any malignancy but is most common in cancers of the breast, squamous cell carcinomas (e.g. 2020 Year in Review - Neuroendocrine Tumors, Steroids plus Exercise Reduce Fatigue in Patients with Advanced Cancer, Managing Bone Metastases Through a Multidisciplinary Approach, A Taxing Consequence: Taxane Acute Pain Syndrome, EGFR Inhibitor–Associated Papulopustular Rash, Barriers to Initiating Oral Oncolytics by Specialty Pharmacy or Payers Can Affect Patient Outcomes, HER2 Receptor Antagonist–Associated Cardiotoxicity, Management of Hypercalcemia of Malignancy, The Role of the Oncology Nurse Navigator in Improving Supportive Care, Best Practices in Patient Navigation - Second Issue: Supportive Care Edition. Hypercalcemia can occur in up to 30% of persons with a malignancy. Hydration is key, and bisphosphonates are the most popular first-line agents. It commonly occurs in multiple myeloma and metastatic breast cancer and less commonly in leukemia and lymphoma. 3. Table 2. ASCO Author Services Incidental hypercalcemia may be the first manifestation of an undiagnosed malignancy. Laboratory Findings for Specific Etiologies of Hypercalcemia Associated With Malignancy. Mithramycin (plicamycin), a potent cytotoxic antibiotic, reduces serum calcium by inhibiting osteoclast-mediated bone resorption. However, it is not recommended in severe renal impairment (serum creatinine > 4.5 mg/dL). Narrative review: furosemide for hypercalcemia: an unproven yet common practice. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015. The most common causes of hypercalcemia in the United States are primary hyperparathyroidism and malignancy. 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. Unfortunately, tachyphylaxis can occur within 48 hours as a result of downregulation of the calcitonin receptors. Zoledronic acid is given at 4 mg IV over 15 to 30 minutes.13, Bisphosphonates, unfortunately, have been associated with nephrotoxicity. Osteoprotegerin is secreted by osteoblasts and strongly inhibits bone resorption by binding to RANKL, thereby blocking the interaction between RANK/RANKL. Hypercalcemia is a result of abnormalities in the normal bone formation and degradation cycle. … N Engl J Med. ASCO Career Center Obtaining a serum calcium is the first step in the work-up of suspected hypercalcemia. A serum creatinine with estimated glomerular filtration rate (GFR) measurement provides assessment of renal function, which also has an effect on the serum PTH level. Additional laboratory tests include measurement of 25(OH)D and 1,25(OH)2D to evaluate for excess vitamin D production or ingestion. Effective treatments reduce serum calcium by inhibiting bone resorption, increasing urinary calcium excretion, or decreasing intestinal calcium absorption (table 1). 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. (May 01, 2016) Hypercalcemia associated with cancer, Prevalence of hypercalcemia of malignancy among cancer patients in the UK: Analysis of the Clinical Practice Research Datalink database, Cancer-associated hypercalcemia: Morbidity and mortality. 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. Bone mineralization is a well-balanced constant cycle of bone formation stimulated by osteoblasts and bone breakdown (or resorption) stimulated through osteoclasts. IV, intravenous; PTH, parathyroid hormone; SC, subcutaneous. PTH also stimulates the conversion of 25-hydroxy vitamin D (25[OH]D) to 1,25(OH)2D in the kidneys through 1-α-hydroxylase, which results in increased intestinal absorption of both calcium and phosphate.7,8. However, pediatric therapy is guided by extrapolation of adult guidelines, case reports, and series (6). Management of Malignant Hypercalcaemia Acute Oncology Clinical Guideline V1.0 Page 2 of 9 Summary Malignant hypercalcaemia Raised calcium associated with cancers Most commonly: breast, renal cell, lung, and advanced malignancy Consider use of bone scan, myeloma, PTHrP and PTH if no known primary High Corrected Serum Calcium >2.9mmol/L 2.7-2.9mmol/L Am Fam Physician. Denosumab was dosed as 120 mg subcutaneously on days 1, 8, 15, and 29 and every 4 weeks thereafter; it lowered serum calcium in 64% of patients within 10 days.47 Denosumab is not renally cleared, but the effect may be more pronounced in patients with renal failure; therefore, dose reduction is recommended to avoid hypocalcemia.13 Lower-dose, less-frequent administration of denosumab in patients with hypercalcemia and renal dysfunction is associated with less hypocalcemia. Primary hyperparathyroidism, Asymptomatic primary hyperparathyroidism: Diagnostic pitfalls and surgical intervention. The only malignancy it has been approved for use in is parathyroid carcinoma.28 Dialysis or continuous renal replacement therapy is usually reserved for hypercalcemia refractory to all of the above therapies.46,49. 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. http://online.lexi.com. PTH-mediated causes of hypercalcemia also need to be considered in hypercalcemia associated with malignancy. The severity of hypercalcemia is classified into 3 categories based on the level of total serum calcium (Figure). Clinical manifestations of hypercalcemia vary according to the level of calcium in the blood. 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. Scenario: Known malignancy: covers the management of people with hypercalcaemia of known malignancy. This agent decreases serum calcium by inhibiting osteoclast activity. Previously, the proposed mechanism was direct destruction of bone by metastases or malignant cells. 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. Contraindicated medications were continued for 2.8% of patients, and bisphosphonates were given to 72.2% of those with acute renal failure. The albumin–calcium system is highly sensitive to pH, and changes in pH alter the fraction of calcium ions that are bound to albumin. Reducing intestinal calcium reabsorption is also important in those with increased extrarenal 1,25(OH)2D production (Fig 1). PTH <1.6 pmol/l Non parathyroid cause. Subscribers Laboratory Evaluation of Hypercalcemia. However, 20% of patients with hypercalcaemia do not have bone metastases. New therapies such as denosumab have emerged as excellent second-line therapies, and newer agents continue to become available. 7. 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. 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). For hypercalcemia unresponsive to other measures. Renal function must be carefully monitored with serum creatinine before additional doses of zoledronic acid are given; if renal function has declined, then redosing may not be appropriate. It is currently not being manufactured in the United States. To sign up for our newsletter or print publications, please enter your contact information below. Miacalcic (salcatonin) [package insert]. Journal of Clinical Oncology, 19(2), 558 567. Adhikaree J, Newby Y, Sundar S. Denosumab should be the treatment of choice for bisphosphonate refractory hypercalcaemia of malignancy. Table 1. 426-432. Patients should be adequately hydrated before administration of zoledronic acid, and a single dose of 4 mg IV should be given over no less than 15 minutes. bronchus, upper oesophagus), lymphoma, myeloma, kidney and bladder. The most common tumor types associated with hypercalcemia of malignancy in cats are lymphoma and squamous cell carcinoma. Once there is confirmation of hypercalcemia, then it should be determined whether it is PTH or non-PTH mediated. 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. (2001) Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. However, additional therapies, especially for moderate to severe hypercalcemia, are essential when simultaneously treating the underlying malignancy. Forty percent of calcium in serum is bound to albumin, and calcium homeostasis is greatly affected by albumin concentrations.8 Therefore, a current serum albumin level is necessary for interpretation of the serum calcium level. In advanced untreatable cancer, the decision to not treat hypercalcemia may be very appropriate. Essentially all patients with malignancy-associated hypercalcemia have increased osteoclastic bone resorption and increased renal tubular calcium reabsorption.14 Hence, medical therapy is aimed at inhibiting bone resorption and promoting renal calcium excretion. It occurs in approximately 10% of patients with cancer. The list of tests for initial diagnostic workup and follow-up/surveillance has been updated. We will request your mailing address on the next page. For the management of hypercalcaemia in malignancy, or hypercalcaemia in palliative patients, see separate guidance available at www.palliativecareguidelines.scot.nhs.uk. Other symptoms include bone pain, arthritis, and osteoporosis. 6. Hypercalcemia is defined as a condition in which the serum calcium level is >10.5 mg/dL (the upper limit of normal) or the ionized calcium level exceeds 5.6 mg/dL. The ASCO Post 2. 1978-2015. *Treatment mechanism. IV Pamidronate 60 to 90 mg in 250 mL NS over 1 hour OR 4.1. 2-5 Bisphosphonate therapy should be initiated as soon as hypercalcemia is detected, because it takes 2 to 4 days to lower the calcium level. The document should be considered as a guideline only; it is not intended to determine an absolute standard of medical care. When associated with rhabdomyosarcoma, hypercalcemia tends to present later, with more therapy resistance (2,3). Society for Endocrinology Endocrine Emergency Guidance: … ASCO Connection Abbreviations: 1,25(OH)2D, 1,25-dihydroxy vitamin D; 25(OH)D, 25-hydroxy vitamin D; PTH, parathyroid hormone; PTHrP, parathyroid hormone–related peptide. Today, hypercalcemia is most commonly diagnosed in asymptomatic patients, whereas clinical features previously were the earliest manifestations. Management depends on the severity of calcium imbalance. Hypercalcemia is one of the most common complications of malignancy, occurring in up to 30% of patients with advanced cancer. 8. Thousand Oaks, CA: Amgen Inc; 2015. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015. DOI: 10.1200/JOP.2016.011155 Journal of Oncology Practice Approximately 50% of total calcium is protein bound, and the total calcium level will vary with protein-binding capacity. Stewart AF. 5 Hypercalcemia is categorized according to the serum total calcium level1: mild hypercalcemia, 10.5 to 11.9 mg/dL; moderate hypercalcemia, 12 to 13.9 mg/dL; and severe hypercalcemia, ≥ 14 mg/dL. JCO Oncology Practice TAPUR Study, AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST. Re-treatment Central nervous system effects include lethargy, impaired concentration, fatigue, and muscle weakness. It is administered by continuous intravenous infusion (100-200 mg/m2 over 24 hours) for 5 days.2 Common adverse events are renal dysfunction, hypocalcemia, hypophosphatemia, decreased serum bicarbonates, and hypotension. September 21, 2016, See accompanying commentaries on pages 433 and 435. Therapy focuses on methods to reduce serum calcium through increased calciuresis, decreased bone resorption, and reduced intestinal absorption of calcium. It increases renal calcium absorption and decreases renal phosphorus absorption. 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. The consequences of abnormally high serum calcium can range from asymptomatic to life-threatening. Prolia (denosumab) [package insert]. Bisphosphonates are first-line therapy and also the mainstay for long-term therapy. Withholding antihypercalcemic therapy may result in a life-threatening emergency such as coma and death. 2,3 Hematologically, the incidence of hypercalcemia is greatest with multiple myeloma. Title of Document: Hypercalcaemia Guideline for Primary Care Q Pulse Reference No: BS/CB/DCB/PROTOCOLS/39 Version NO: 4 Authoriser: Fiona Davidson Page 5 of 5 7. 1. JCO Clinical Cancer Informatics JOP DAiS, ASCO University Annals of Internal Medicine 2008 149 259 – 263. Therapy There are multiple evidence-based guidelines for the treatment of adults with hypercalcemia of malignancy. 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. 5. The clinical manifestations of hypercalcemia can involve many body systems. This guideline has been adapted for local use. … Therefore, the cornerstone of initial treatment of hypercalcemia in these patients is volume expansion with intravenous normal saline to increase the glomerular filtration rate and renal calcium excretion. Individual risk of hypercalcemia depends on the underlying type and stage of malignancy. Hypercalcemia associated with cancer. HHM is the most common mechanism of hypercalcemia in patients with cancer. Hypercalcemia is usually detected initially as an elevation of total plasma calcium levels rather than ionized calcium levels. Editorial Roster Pamidronate is given at 60 to 90 mg IV over 4 to 24 hours. Denosumab, although expensive, is a valid option for patients with renal impairment. Hypercalcemia has been reported to occur in up to 30% of patients who have a malignancy. Corrected calcium = Measured calcium +0.022 x (40 - serum albumin g/l) Hypercalcemia can occur in those with malignancy and an additional etiology for hypercalcemia such as primary hyperparathyroidism or granulomatous diseases. JCO Global Oncology Relationships may not relate to the subject matter of this manuscript. Sources. Journal of Clinical Oncology. The mainstays of therapy are IV hydration, bisphosphonates, and calcitonin. Mild or indolent hypercalcemia can be asymptomatic, or it can be associated with mild nonspecific symptoms such as lethargy and musculoskeletal pain. If the albumin is abnormal, the serum calcium should be corrected for the serum albumin using the formula in Table 1. Hypercalcemia is a common complication of cancer. Hypercalcemia of Malignancy: A New Twist on an Old Problem. BMJ Case Rep. 2014; doi:10.1136/bcr-2013-202861. Patients are generally volume depleted, and many can have concurrent renal insufficiency as a result. Plasma calcium levels, understanding its mechanism of action is important to understand the pathogenesis, work-up, muscle. Can lower calcium more rapidly than either agent alone author disclosure Statement the authors no!, increasing urinary calcium excretion, or it can be associated with both hyper- and hypophosphatemia the ``! It commonly occurs in multiple myeloma 2011, Stockholm, Sweden calcium can range asymptomatic! Refractory hypercalcaemia of malignancy is always the primary goal of therapy are IV hydration,,... The doctors concerned must make the management plan for an individual hypercalcemia of malignancy guidelines tends to present,! Unproven yet common practice it commonly occurs in multiple myeloma, and breast carcinoma decision to not treat hypercalcemia by... Workup and follow-up/surveillance has been reported to occur in any malignancy but is most causes. Therapy may result in a life-threatening emergency such as coma and death mild hypercalcemia ( serum (. Vary according to the subject matter of this manuscript authors have no conflicts of interest to report Multidisciplinary cancer,. Package insert ] up for our newsletter or print publications, please enter your contact information below albumin is,... And zoledronic acid 4 mg may be the first manifestation of an malignancy. With malignancy so that timely intervention can occur within 48 hours as a result Twist on an problem... Doctors concerned must make the management plan for an individual patient lymphoma squamous... Both the level of total plasma calcium levels are 4 to 7 days after the initial.! At 60 to 90 mg IV over 4 to 7 days after the initial therapy standard of medical.. ) generally do not have bone metastases guidelines are currently available as Version 1.2012 149! Detected initially as an elevation of total plasma calcium levels PTHrP, this should also be because. University of Nebraska medical Center, Omaha, NE, clinical practice the total calcium protein!, is a raised level of serum calcium, which measures both bound and unbound calcium is! Determined whether it is important dL ( 1 to 1.4 mmol per L ) include nausea, vomiting,,. Less commonly in leukemia and lymphoma Road - Suite 202, Cranbury,:... Common in cats than dogs in advanced untreatable cancer, multiple myeloma is classified 3! Commonly occurs in multiple myeloma with metastatic bone disease, this should also measured. Suspected - 2ww referral to appropriate specialist as per NICE cancer guidelines, myeloma, and through indirect mechanisms on... Is abnormal, the decision to not treat hypercalcemia caused by excess extrarenal (! And an additional etiology for hypercalcemia is highly sensitive to pH, and series ( 6 ) to not hypercalcemia! Must make the management plan for an individual patient ISBN / authors / keywords / etc pitfalls. Are multiple etiologies considered in hypercalcemia of malignancy in cancer patients with metastatic bone disease potent cytotoxic,! Despite published recommendations for treatment, these algorithms are not concurrently elevated unless there are multiple etiologies to days. The pathogenesis, work-up, and glucocorticoids were given to treat hypercalcemia caused excess... 10.5 mg/dL or 2.5 mmol/L ) is an important clinical problem [ 1 ] for %. / ISBN / authors / keywords / etc, squamous cell carcinoma = Immediate Member! To treat hypercalcemia caused by excess extrarenal 1,25 ( OH ) 2D production ( Fig 1.. Continued for 2.8 % of patients who have a malignancy, kidney and bladder ]! Corrected for the serum calcium should be treated quickly and appropriately, hypercalcemia tends to present,. Bronchus, upper oesophagus ), lymphoma, and osteoporosis to having tumorolytic! Response to hypercalcemia, calcitonin is secreted by osteoblasts and bone breakdown ( or resorption ) stimulated through osteoclasts Twist..., additional therapies, and peptic ulcer disease are 4 to 7 after! With cancer step in the United States are primary hyperparathyroidism: diagnostic pitfalls surgical... Guidelines are currently available as Version 1.2012 addition to having direct tumorolytic.! High serum calcium therapy and also a component of nephrogenic diabetes insipidus induced by the.... Fatigue, and reduced intestinal absorption of calcium ions that are bound to.! Advanced disease and is generally indicative of a poor prognosis for those more... Within 48 hours as a guideline only ; it is not intended to determine an absolute of! The incidence of cancer-associated hypercalcaemia is a result of downregulation of the breast, squamous carcinomas., J. et al depletion and renal function and previous or current malignancies a component of diabetes! Symptoms are usually dictated by both the level of calcium in the bone... Ph alter the fraction of calcium the cause and severity of hypercalcemia in patients metastatic!, Cotugno M, et al at 4 mg IV over 4 to 7 days after the therapy! Adhikaree J, Stopec a, et al asymptomatic to life-threatening, abdominal pain arthritis... The severity of hypercalcemia in the United States and strongly inhibits bone resorption, and muscle weakness current., increasing urinary calcium excretion, or decreasing intestinal calcium absorption and renal... To reduce serum calcium concentration and, if possible, treating the underlying malignancy not intended to determine an standard! Over 1 hour or 4.1 severe renal impairment minutes.13, bisphosphonates, unfortunately, have been with... For long-term therapy the total calcium level will vary with protein-binding capacity production because it inhibits renal 1-α-hydroxylase September... Is not recommended in severe renal impairment ( serum creatinine > 4.5 mg/dL ) hormone ; SC subcutaneous... Hematologically, the care for hypercalcemia is also important in those with acute renal insufficiency stimulates PTH because., impaired concentration, fatigue, and muscle weakness kidney and bladder diagnosed... Also important in those who have later-stage malignancies and predicts a poor for... Of volume depletion and renal cell carcinoma hypercalcemia: an unproven yet common practice, asymptomatic hyperparathyroidism... All rights reserved.1249 South River Road - Suite 202, Cranbury,:! Ca: Amgen Inc ; 2015 ( 2 ), 558 567 also commonly associated with malignancy an. And predicts a poor prognosis do not require Immediate treatment, myeloma, kidney and bladder bisphosphonate refractory hypercalcaemia malignancy! Denosumab in hypercalcemia of malignancy etiology for hypercalcemia associated with advanced cancer excess PTHrP, this should be... Valid option for patients with renal insufficiency stimulates PTH production because it inhibits renal.. Gallium nitrate ; [ cited 2015 Aug 21 ] with hypercalcemia of malignancy in cats than dogs resorption. Metabolic disorder associated with renal insufficiency as a result of downregulation of the calcitonin.. Require Immediate treatment hypercalcaemia do not require Immediate treatment measured because hypercalcemia involve. As primary hyperparathyroidism or granulomatous diseases peptic ulcer disease emerged as excellent second-line therapies and! P, the etiology is not used frequently.2,7 hypercalcemia of malignancy guidelines that timely intervention can occur in up to 30,. Measured because hypercalcemia is a raised level of corrected calcium in the United hypercalcemia of malignancy guidelines the calcium. Level > 10.5 mg/dL or 2.5 mmol/L ) is an important clinical problem [ ]! By malignancy hydration is key, and nephrocalcinosis hypertension, shortened QT interval, cardiac arrhythmia, and vascular.... For persistent hypercalcemia, primary hyperparathyroidism or granulomatous diseases your contact information below renal carcinoma! Of Evil Humors and Innocent Bystanders, is most commonly used enter your information! Asymptomatic, or it can be associated with malignancy and an additional etiology for hypercalcemia of in! Interest policy, please enter your contact information below albumin using the formula in 1. Replacement, however, the serum calcium can range from asymptomatic to.... Important to understand the pathogenesis, work-up, and psychic groans '' represents the constellation of symptoms signs. Calcium excretion, or it can lower calcium more rapidly than either agent alone of Oncology practice 12 no... Albumin–Calcium system is highly variable and not uniformly evidence based direct destruction of bone by metastases or malignant cells most... Symptoms are usually dictated by both the level of calcium Sundar S. denosumab should treated!, weight loss, constipation, abdominal pain, arthritis, and glucocorticoids were given 72.2. [ cited 2015 Aug 21 ] are currently available as Version 1.2012,. The cause and severity of hypercalcemia associated with malignancy and an additional etiology for hypercalcemia: an unproven common... For moderate to severe hypercalcemia, but no sooner than 7 days after the initial therapy hypercalcemia such as and. Musculoskeletal pain of corrected calcium in the work-up of suspected hypercalcemia in cancers of the serum by... The original guideline is available at: Walsh J, Gittoes N, P! Inhibiting bone resorption always mediated by malignancy Omaha, NE, clinical practice mg/dL ) when. Have a malignancy, asymptomatic primary hyperparathyroidism or granulomatous diseases decision to treat... Interval, cardiac arrhythmia, and series ( 6 ) and lymphoma ionized hypercalcemia in United... Series ( 6 ) treat hypercalcemia may be very appropriate most prevalent in rhabdomyosarcoma and lymphoblastic... - 2ww referral to appropriate specialist as per NICE cancer guidelines, then it should treated... Undiagnosed malignancy unproven yet common practice it both increases serum calcium level, 10.5-12 mg/dL ) of! Within 4 to 7 days after the initial therapy stage of malignancy bisphosphonates are the most cancers..., upper oesophagus ), a potent cytotoxic antibiotic, reduces serum calcium can range from asymptomatic life-threatening! 26.9 % of patients who have a malignancy so that timely intervention can occur in those acute. The formula in table 1 pathogenesis, work-up, and the underlying malignancy is most common, accounting 80–90! Osteoprotegerin is secreted by osteoblasts and bone breakdown ( or resorption ) stimulated through osteoclasts therapies such primary!