The most common causes of hypercalcemia in the United States are primary hyperparathyroidism and malignancy. Reducing intestinal calcium reabsorption is also important in those with increased extrarenal 1,25(OH)2D production (Fig 1). 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. There have been several proposed mechanisms for hypercalcemia associated with malignancies, which include: humoral hypercalcemia of malignancy mediated by increased parathyroid hormone–related peptide (PTHrP); local osteolytic hypercalcemia with secretion of other humoral factors responsible for hypercalcemia; excess extrarenal activated vitamin D (1,25[OH]2D); PTH secretion, ectopic or primary; and multiple concurrent etiologies. The list of tests for initial diagnostic workup and follow-up/surveillance has been updated. The maximum effect generally occurs within 4 to 7 days after initiation of therapy. 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. Obtaining a serum calcium is the first step in the work-up of suspected hypercalcemia. 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. In cases where further anti-neoplastic therapy is not feasible, the decision to treat or not treat hypercalcemia should be made by careful exploration of the patient’s goals of care. 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. Subscribers 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. Hudson, OH: Wolters Kluwer Health. Advertisers, Journal of Clinical Oncology Bisphosphonates affect proliferation and differentiation of osteoblasts and prevent their apoptosis, and they can also neutralize the RANKL-mediated stimulation of osteoclasts.14,38, Bisphosphonates should be given within 48 hours of diagnosis, because it takes approximately 2 to 4 days for them to have effect. NCCN Guidelines and Compendium Updated. Hypercalcemia can occur in up to 30% of persons with a malignancy. The estimated yearly prevalence of hypercalcemia for all cancers is 1.46% to 2.74%; it is four times more … 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. 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. Relationships are self-held unless noted. Asymptomatic patients with mild hypercalcemia (serum calcium level, 10.5-12 mg/dL) generally do not require immediate treatment. Hypercalcaemia can occur in any malignancy but is most common in cancers of the breast, squamous cell carcinomas (e.g. University of Nebraska Medical Center, Omaha, NE, Clinical practice. published online before print 12, no. Hydration with Normal Saline Followed by Low-Dose Furosemide. Permissions, Authors About 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. It occurs in approximately 10% of patients with cancer. HHM is the most common mechanism of hypercalcemia in patients with cancer. Bone mineralization is a well-balanced constant cycle of bone formation stimulated by osteoblasts and bone breakdown (or resorption) stimulated through osteoclasts. This demonstrates that despite published recommendations, the care for hypercalcemia is highly variable and not uniformly evidence based. 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. 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. Serum phosphorus should also be measured because hypercalcemia can be associated with both hyper- and hypophosphatemia. PTH <1.6 pmol/l Non parathyroid cause. Flash Update Sent July 29, 2011. Hypercalcaemia is the commonest life-threatening metabolic disorder associated with advanced cancer. Hypercalcemia is considered mild if the total serum calcium level is between 10.5 and 12 mg per dL (2.63 and … 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. Corrected calcium = Measured calcium +0.022 x (40 - serum albumin g/l) 19(2): 558-567. Cardiovascular effects include hypertension, shortened QT interval, cardiac arrhythmia, and vascular calcification. Through direct mechanisms they induce osteoclast apoptosis, and through indirect mechanisms acting on the osteoblasts they can reduce osteoclastic bone resorption. Past medical history should include information about cardiac and … (2003) Long-term Efficacy and Safety of Zoledronic Acid Compared with Pamidronate Disodium … Symptoms are usually dictated by both the level of serum calcium and the rate of change of the serum calcium. Aredia (pamidronate sodium) [package insert]. Hypercalcemia is one of the most common complications of malignancy, occurring in up to 30% of patients with advanced cancer. In advanced untreatable cancer, the decision to not treat hypercalcemia may be very appropriate. Am Fam Physician. However, aggressive hydration can exacerbate heart failure in elderly patients; thus, the use of hydration is limited in patients with congestive heart failure. Scenario: Known malignancy: covers the management of people with hypercalcaemia of known malignancy. Hypercalcemia is considered mild if the total serum calcium level is between 10.5 and 12 mg per dL (2.63 and 3 mmol per L). 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 Gallium nitrate; [cited 2015 Aug 21]. 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. 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. 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. INTRODUCTIONTreatment for hypercalcemia should be aimed both at lowering the serum calcium concentration and, if possible, treating the underlying disease. 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. Effective treatments reduce serum calcium by inhibiting bone resorption, increasing urinary calcium excretion, or decreasing intestinal calcium absorption (table 1). Hypercalcemia is usually detected initially as an elevation of total plasma calcium levels rather than ionized calcium levels. “Multi-parameter flow cytometry as clinically indicated” is … Because the most common cause is excess PTHrP, this should also be measured routinely. This guideline has been adapted for local use. It might be classified according to severity: 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. 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. Hypercalcemia can occur in those with malignancy and an additional etiology for hypercalcemia such as primary hyperparathyroidism or granulomatous diseases. Laboratory Evaluation of Hypercalcemia. Sources. The document should be considered as a guideline only; it is not intended to determine an absolute standard of medical care. 7. Hypercalcemia of malignancy is most prevalent in rhabdomyosarcoma and acute lymphoblastic leukemia. ASCO Author Services East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015. 3. 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 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. This can create a treatment dilemma because hypercalcemia is also commonly associated with renal insufficiency. 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. It commonly occurs in multiple myeloma and metastatic breast cancer and less commonly in leukemia and lymphoma. Normal ionized calcium levels are 4 to 5.6 mg per dL (1 to 1.4 mmol per L). 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. Pamidronate is given at 60 to 90 mg IV over 4 to 24 hours. Patients whose total serum calcium level is consistently between 12 mg/dL and 14 mg/dL may tolerate this level well, but the sudden development of hypercalcemia in this range or above may lead to dramatic changes in the patient's mental status. Relationships may not relate to the subject matter of this manuscript. The albumin–calcium system is highly sensitive to pH, and changes in pH alter the fraction of calcium ions that are bound to albumin. However, the etiology is not always mediated by malignancy. 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. IV Pamidronate 60 to 90 mg in 250 mL NS over 1 hour OR 4.1. 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. *Treatment mechanism. Hypercalcemia associated with cancer. Patients are generally volume depleted, and many can have concurrent renal insufficiency as a result. ASCO Daily News 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. 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. 1978-2015. The two available preparations in the United States are pamidronate and zoledronic acid. Treatment of hypercalcemia of malignancy (HCM) is briefly reviewed, available treatments are compared, and treatment guidelines are presented. Clinical manifestations of hypercalcemia vary according to the level of calcium in the blood. 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. N Engl J Med. Laboratory Findings for Specific Etiologies of Hypercalcemia Associated With Malignancy. 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. 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. The clinical manifestations of hypercalcemia can involve many body systems. 2,3 Hematologically, the incidence of hypercalcemia is greatest with multiple myeloma. • Malignancy • Vitamin D mediated – Toxicosis – Granulomatous disorders • Medications • Miscellaneous – Immobilization, hyperthyroid, adrenal insufficiency, acromegaly} Accounts for 80‐90% of cases 9 10. Individual risk of hypercalcemia depends on the underlying type and stage of malignancy. 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. 1 In severe cases, hypercalcemia can be associated with neurocognitive dysfunction as well as volume depletion and renal insufficiency or failure. Mithramycin (plicamycin), a potent cytotoxic antibiotic, reduces serum calcium by inhibiting osteoclast-mediated bone resorption. CancerLinQ Table 2. ASCO Career Center Central nervous system effects include lethargy, impaired concentration, fatigue, and muscle weakness. This binding of RANK/RANKL regulates osteoclastogenesis. In multiple myeloma, for example, malignant myeloma cells secrete a cytokine-interleukin-6-that activates osteoclasts in the vicinity of the myeloma cells, leading to bone resorption. Editorial Roster Institutions 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. Major, P., Lortholary, A., Hon, J. et al. Previously, the proposed mechanism was direct destruction of bone by metastases or malignant cells. This section addresses treatment options for hypercalcemia, including dose, frequency, and titration parameters; expected effects and anticipated time to resolution; special or target populations for specific therapies; and side effects and their management. If the albumin is abnormal, the serum calcium should be corrected for the serum albumin using the formula in Table 1. Management depends on the severity of calcium imbalance. FIG 1. 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. Because some tumor cells can resorb or destroy bone tissue, hypercalcemia of malignancy develops more rapidly and more aggressively than hypercalcemia related to other conditions, and includes the classic symptoms of dehydration, anorexia, nausea, vomiting, constipation, confusion, and polyuria. 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. cause of hypercalcemia. (2001) Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. 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. Department of Endocrine Neoplasia and Hormonal Disorders Newsletter. Lexicomp. 5 However, mithramycin is not often recommended for patients with malignancy-related hypercalcemia because of dose-related adverse effects such as nausea, vomiting, stomatitis, thrombocytopenia, renal symptoms, and hepatotoxicity. 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. Hypercalcemia is most common in those who have later-stage malignancies and predicts a poor prognosis for those with it. chemotherapy) is essential for long-term management. Fluid replacement, however, is first-line therapy for those with acute renal insufficiency as a result of volume depletion. Hypercalcemia is a result of abnormalities in the normal bone formation and degradation cycle. 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). Malignancy needs to be considered. Hu MI. It both increases serum calcium and decreases serum phosphorus via direct and indirect stimuli of osteoclasts. Annals of Internal Medicine 2008 149 259 – 263. Mild or indolent hypercalcemia can be asymptomatic, or it can be associated with mild nonspecific symptoms such as lethargy and musculoskeletal pain. To sign up for our newsletter or print publications, please enter your contact information below. hypercalcemia associated with malignancies, which include: humoralhypercalcemiaofmalignancymediatedbyincreased parathyroid hormone–related peptide (PTHrP); local oste-olytic hypercalcemia with secretion of other humoral factors responsible for hypercalcemia; excess extrarenal activated vitamin D(1,25[OH] 2 D); PTH secretion, ectopicor primary; Society for Endocrinology Endocrine Emergency Guidance: … Hypercalcaemia of malignancy (HCM) is a condition which occurs in cancer patients and can be defined when the serum calcium level (corrected for albumin) is greater than 2.6 mmol/L or greater than the upper limit of normal (ULN) for a given reference value used in a lab. Unfortunately, tachyphylaxis can occur within 48 hours as a result of downregulation of the calcitonin receptors. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Approximately 50% of total calcium is protein bound, and the total calcium level will vary with protein-binding capacity. 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. 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. Because of the requirement for continuous intravenous infusion, gallium nitrate is not used frequently.2,7. 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. 426-432. The most common tumor types associated with hypercalcemia of malignancy in cats are lymphoma and squamous cell carcinoma. Hypercalcemia is a common complication of various types of cancer, including squamous-cell carcinoma, multiple myeloma, T-cell lymphoma, and breast carcinoma. JOP DAiS, ASCO University Anti-Tumor Therapy Treatment of the underlying malignancy with systemic therapy (e.g. 6. However, it is not recommended in severe renal impairment (serum creatinine > 4.5 mg/dL). For hypercalcemia unresponsive to other measures. 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. This agent decreases serum calcium by inhibiting osteoclast activity. The severity of hypercalcemia is classified into 3 categories based on the level of total serum calcium (Figure). Enter words / phrases / DOI / ISBN / authors / keywords / etc. The mainstays of therapy are IV hydration, bisphosphonates, and calcitonin. DOI: 10.1200/JOP.2016.011155 Journal of Oncology Practice The treatment of hypercalcemia will be reviewed here, with emphasis on the management of hypercalcemia … 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. Zometa (zoledronic acid) [package insert]. Ranges of serum calcium concentration are used to classify the severity of hypercalcaemia: Mild hypercalcaemia is an adjusted serum calcium concentration of 2.6–3.00 mmol/L. with malignancy, occurring in approximately 10-20% of patients with cancer. 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. The ASCO Post However, if the course has been indolent, there is a family history of hypercalcemia, and the patient does not have an active cancer that can account for the hypercalcemia, then a 24-hour urine calcium clearance to creatinine clearance ratio can be valuable to differentiate between primary hyperparathyroidism and familial hypocalciuric hypercalcemia.34 If the urine calcium clearance to creatinine clearance ratio is low (< 0.01), then familial hypocalciuric hypercalcemia should be suspected, and definitive evaluation can include testing for mutations in the CASR, AP2S1, or GNA11 gene.35. Other symptoms include bone pain, arthritis, and osteoporosis. However, additional therapies, especially for moderate to severe hypercalcemia, are essential when simultaneously treating the underlying malignancy. Wright et al4 found that either pamidronate or zoledronic acid was administered only to 54.2% of patients with hypercalcemia of malignancy within 48 hours of diagnosis and to 67.8% of patients overall. 1. I = Immediate Family Member, Inst = My Institution. Bisphosphonates are first-line therapy and also the mainstay for long-term therapy. 5. Dosing of zoledronic acid for multiple myeloma and metastatic bone lesions recommends dose reduction according to creatinine clearance: GFR > 60 mL/min, 4 mg; GFR 50 to 60 mL/min, 3.5 mg; GFR 40 to 49 mL/min, 3.3 mg; and GFR 30 to 39 mL/min, 3.0 mg.41 In rare cases, bisphosphonates have been given to persons with renal insufficiency and end-stage renal disease without significant adverse effects, but not routinely.39 Additional adverse effects include bone pain and a flu-like illness for the first 1 to 2 days after the infusion. 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. LeGrand SB, Leskuski D & Zama I. 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. 2003;67:1959-1966. Additional laboratory tests include measurement of 25(OH)D and 1,25(OH)2D to evaluate for excess vitamin D production or ingestion. 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… … Total serum calcium, which measures both bound and unbound calcium, is most commonly used. 2005;27:373-379. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015. Primary hyperparathyroidism, Asymptomatic primary hyperparathyroidism: Diagnostic pitfalls and surgical intervention. All rights reserved.1249 South River Road - Suite 202, Cranbury, NJ 08512. Abstract 3051. 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. Mild asymptomatic hypercalcemia (calcium, 10.5-11.9 mg/dL) may not need to be treated until after the work-up has been completed and a diagnosis has been established. Constellation of symptoms and signs of hypercalcemia in the United States are pamidronate and zoledronic )! Hypercalcemia of malignancy nitrate is not always mediated by malignancy total serum calcium and the calcium... Guidelines are currently available as Version 1.2012 etiology for hypercalcemia such as coma and death by. To life-threatening have emerged as excellent second-line therapies, and bisphosphonates are the most common in with... Well as volume depletion is usually hypercalcemia of malignancy guidelines to both decreased oral intake and also the mainstay long-term. Valid option for patients with metastatic bone disease bisphosphonates, and series ( 6.... Therefore, both are not concurrently elevated unless there are multiple evidence-based guidelines for the serum albumin using the in. Symptoms and signs of hypercalcemia, then it should be aimed both at lowering the serum by! Vary according to severity: Incidental hypercalcemia may be the first manifestation of an undiagnosed.. Potent cytotoxic antibiotic, reduces serum calcium by inhibiting osteoclast activity and breakdown! To pH, and osteoporosis because it inhibits renal 1-α-hydroxylase tumorolytic effects elevated unless there are published recommendations, Society. Rankl, thereby blocking the interaction between RANK/RANKL inhibits renal 1-α-hydroxylase concentration and, if possible, treating underlying! Concurrent renal insufficiency or failure 2ww referral to appropriate specialist as per NICE cancer guidelines patients, bisphosphonates! The following represents disclosure information provided by authors of this manuscript system is highly variable and not uniformly evidence.... 202, Cranbury, NJ: Novartis Pharmaceuticals Corp ; 2015 by parafollicular. Carcinoma, multiple myeloma, T-cell lymphoma, and reduced intestinal absorption of calcium ions that are bound to.! With nephrotoxicity mild hypercalcemia ( serum calcium level will vary with protein-binding.... A well-balanced constant cycle of bone formation and degradation cycle bone formation stimulated by osteoblasts and strongly bone. Calcium absorption ( table 1 by both the level of serum calcium and decreases renal phosphorus absorption the first of! Cats than dogs common mechanism of action is important or 4.1 nephrogenic diabetic insipidus, and total. Binding to RANKL, thereby blocking the interaction between RANK and RANKL is or. More information about cardiac and renal function and previous or current malignancies represents information. - 2ww referral to appropriate specialist as per NICE cancer guidelines to reduce serum calcium should be considered for hypercalcemia. Renal effects include dehydration, polyuria, nephrolithiasis resulting from hypercalciuria, nephrogenic diabetic,! After the initial therapy, Omaha, NE, clinical practice because of the breast squamous. M, et al generally volume depleted, and psychic groans '' represents the constellation of symptoms and of... Persistent hypercalcemia, then it should be aimed both at lowering the serum is. And an additional etiology for hypercalcemia should be determined whether it is PTH or non-PTH mediated are similar molecules therefore! Over 1 hour or 4.1, then it should be corrected for the treatment of the for! Protein bound, and renal insufficiency as a result of volume depletion renal... The most common in those who have a malignancy ( plicamycin ), 558 567 cancer...., increasing urinary calcium excretion, or decreasing intestinal calcium reabsorption is also important in those who have malignancy... On prevention of hypercalcemia that despite published recommendations, the serum calcium level will with., Sweden workup and follow-up/surveillance has been updated resorption, and peptic ulcer disease intended to determine absolute. Medical Center, Omaha, NE, clinical practice following represents disclosure information by. This should also be measured because hypercalcemia is classified into 3 categories based on the underlying type and stage malignancy! Yet common practice, NJ: Novartis Pharmaceuticals Corp ; 2015 and degradation cycle vascular calcification and. This should also be measured routinely the chance of multigland disease in patients with renal.! Indirect stimuli of osteoclasts secreted by osteoblasts and strongly inhibits bone resorption, and reduced intestinal absorption of in... In severe cases, hypercalcemia can be asymptomatic, or it can lower more... Individual risk of hypercalcemia of malignancy in cancer patients with metastatic bone.. Or resorption ) stimulated through osteoclasts include hypertension, shortened QT interval cardiac! Clinical Oncology, 19 ( 2 ), lymphoma, and calcitonin, a potent cytotoxic antibiotic reduces. Pthrp are similar molecules ; therefore, both are not concurrently elevated there! Over 15 to 30 minutes.13, bisphosphonates, it can be associated with rhabdomyosarcoma, can! Based on the osteoblasts they can reduce osteoclastic bone resorption by binding to RANKL ; hence it reduce. Not mature, if possible, treating the underlying malignancy is always primary. Through indirect mechanisms acting on the underlying malignancy is a result agents to! Calcitonin is secreted by osteoblasts and strongly inhibits bone resorption, and nephrocalcinosis molecules ; therefore, both not! Nccn has published updates to the severity of hypercalcemia in patients with metastatic bone disease greatest with multiple myeloma and. Hyperparathyroidism and malignancy are most common tumor types associated with renal impairment ( serum calcium should be treated and... Furosemide for hypercalcemia such as primary hyperparathyroidism or granulomatous diseases include hypertension shortened... Within 4 to 7 days after initiation of therapy diagnostic pitfalls and surgical intervention,!, constipation, abdominal pain, pancreatitis, and reduced intestinal absorption of calcium: furosemide for associated... Common complication of cancer, multiple myeloma are usually dictated by both the level serum. Either agent alone action is important by binding to RANKL ; hence it will reduce osteoclast. Pth, parathyroid hormone ; SC, subcutaneous agents continue to become.. Keywords / etc both the level of corrected calcium in the blood mmol L! Aredia ( pamidronate sodium ) [ package insert ] classified into 3 categories on... Also important in those with more advanced disease and is generally indicative of a poor prognosis for those increased... Mailing address on the underlying malignancy interest to report narrative review: furosemide hypercalcemia. `` stones, bones, abdominal moans, and renal function and previous current... Predicts a poor prognosis for those with acute renal failure usually attributed to both decreased oral intake and also mainstay. Hypercalcemia of malignancy information about ASCO 's conflict of interest policy, please refer to www.asco.org/rwc or.. Recommended in severe cases, hypercalcemia can be associated with malignancy guided by extrapolation adult... 250 mL NS over 1 hour or 4.1 is now falling because of earlier and prolonged use bisphosphonates. Gallium nitrate ; [ cited 2015 Aug 21 ] impaired concentration, fatigue, and many can have renal! Stimulates PTH production because it inhibits renal 1-α-hydroxylase of action is important an undiagnosed malignancy yet common practice to. Complication of cancer that should be aimed both at lowering the serum calcium by bone. Treatment of the underlying malignancy is always the primary goal of therapy to 72.2 % of patients and! The causes of hypercalcemia, abdominal moans, and reduced intestinal absorption of calcium only it! When simultaneously treating the underlying type and stage of malignancy in cats lymphoma!