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. Usual supportive care for hypercalcemia includes removing calcium intake from any sources (eg, intravenous or oral calcium supplements), increasing oral free water intake, discontinuing medications and supplements that cause hypercalcemia (thiazide diuretics, lithium, vitamin D, calcium carbonate therapy), increasing weight-bearing ambulation/activities, and discontinuing sedative drugs and analgesics.1 Symptomatic patients whose serum calcium level exceeds 12 mg/dL or asymptomatic persons whose level exceeds 14 mg/dL should be immediately and aggressively treated with antihypercalcemic therapy: saline rehydration followed by loop diuretics, calcitonin, bisphosphonates, or denosumab.2,4 For the majority of cancer patients with HHM or local osteolytic hypercalcemia, intravenous bisphosphonates or subcutaneous/intramuscular calcitonin or subcutaneous denosumab can be used to inhibit osteoclast-mediated bone resorption. However, the etiology is not always mediated by malignancy. Hypercalcemia is a result of abnormalities in the normal bone formation and degradation cycle. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015. The normal range for total serum calcium is 8.5 mg/dL to 10.5 mg/dL, and the normal range for ionized calcium is 4 mg/dL to 5.6 mg/dL. For hypercalcemia less than3.5 mmol/L with symptoms. with malignancy, occurring in approximately 10-20% of patients with cancer. 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. Rarely, vitamin A toxicity can result in hypercalcemia; thus serum vitamin A levels can be a consideration if other etiologies are not discovered. Hu MI. (2001) Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. Humoral hypercalcemia of malignancy refers specifically to PTHrP-mediated hypercalcemia and was first proposed by Fuller Albright in 1941.9 It is estimated to account for 80% of hypercalcemia in cancer patients.1,5 This is most commonly seen in squamous cell carcinomas such as head and neck, esophageal, cervical, lung,1 and colon cancers10 in addition to renal cell,11 bladder, breast, endometrial, and ovarian cancers,1 and it is rarely seen in pancreatic neuroendocrine tumors.12 PTHrP is structurally similar to PTH and, like PTH, it enhances renal tubular reabsorption of calcium while simultaneously increasing urinary phosphorus excretion. Contact Us Hypercalcemia is most common in those who have later-stage malignancies and predicts a poor prognosis for those with it. 5. Hypercalcemia of malignancy: current & future directions. cause of hypercalcemia. Sources. Local osteolytic hypercalcemia is typically associated with breast cancer, multiple myeloma, and lymphoma.1 Moreover, osteoblasts secrete a receptor activator of nuclear factor kappa-B ligand (RANKL), which activates osteoclasts and promotes secretion of insulin-like growth factor-1, which then increases calcium levels, which is a point of target for medications to inhibit RANKL.3. The doctors concerned must make the management plan for an individual patient. 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. N Engl J Med. However, pediatric therapy is guided by extrapolation of adult guidelines, case reports, and series (6). This demonstrates that despite published recommendations, the care for hypercalcemia is highly variable and not uniformly evidence based. 3. 7. Hypercalcaemia is a raised level of corrected calcium in the blood. In cats, idiopathic hypercalcemia appears to be the most frequent cause of a high total calcium concentration, followed by renal failure and malignancy. NCCN has published updates to the NCCN Guidelines and the NCCN Compendium® for Multiple Myeloma. It is the commonest life-threatening metabolic disorder in cancer patients, most frequently occurring in myeloma, breast, renal, lung and thyroid cancers. Bisphosphonates are first-line therapy and also the mainstay for long-term therapy. IV, intravenous; PTH, parathyroid hormone; SC, subcutaneous. September 21, 2016. 6. 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. For hypercalcemia unresponsive to other measures. CancerLinQ 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. Bone mineralization is a well-balanced constant cycle of bone formation stimulated by osteoblasts and bone breakdown (or resorption) stimulated through osteoclasts. Serum phosphorus should also be measured because hypercalcemia can be associated with both hyper- and hypophosphatemia. 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. A practical approach to hypercalcemia. Zometa (zoledronic acid) [package insert]. Most patients with hypercalcemia associated with malignancy are dehydrated as a result of renal dysfunction induced by hypercalcemia and by decreased oral fluid intake resulting from nausea and vomiting. The most common cancers are lung cancer, multiple myeloma, and renal cell carcinoma. However, additional therapies, especially for moderate to severe hypercalcemia, are essential when simultaneously treating the underlying malignancy. If the interaction between RANK and RANKL is disrupted or blocked, then the osteoclasts do not mature. Approximately 50% of total calcium is protein bound, and the total calcium level will vary with protein-binding capacity. 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. 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. 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. 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.
Thus, understanding its mechanism of action is important. Normal ionized calcium levels are 4 to 5.6 mg per dL (1 to 1.4 mmol per L). Therapy There are multiple evidence-based guidelines for the treatment of adults with hypercalcemia of malignancy. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2015. 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. 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. … Hydration is key, and bisphosphonates are the most popular first-line agents. 2015;21:143-147. Glucocorticoids are also given to treat hypercalcemia caused by excess extrarenal 1,25(OH)2D and multiple myeloma. Renal effects include dehydration, polyuria, nephrolithiasis resulting from hypercalciuria, nephrogenic diabetic insipidus, and nephrocalcinosis. Denosumab is a human monoclonal antibody to RANKL; hence it will reduce the osteoclast activity and bone resorption. 2,3 Hematologically, the incidence of hypercalcemia is greatest with multiple myeloma. 426-432.
Past medical history should include information about cardiac and … When associated with rhabdomyosarcoma, hypercalcemia tends to present later, with more therapy resistance (2,3).
IV Zoledronic acid 4 mg in 100 mL NS over 15 minutes (note: see #7 initial dose modification if renal dysfunction) 5. 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 The ASCO Post 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. 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. … NCCN Guidelines and Compendium Updated. 1. FIG 1. Hudson, OH: Wolters Kluwer Health. Although rare, this can result in pseudohypercalcemia—for example, in patients with hyperalbuminemia secondary to dehy… Institutions 1-3 Hypercalcemia may be associated with any malignancy type, but is more frequently observed in carcinomas of the breast, lung, kidney, head and neck. Hypercalcemia associated with cancer. Retreatment with zoledronic acid 4 mg may be considered for persistent hypercalcemia, but no sooner than 7 days after the initial therapy. The clinical manifestations of hypercalcemia can involve many body systems. Hypercalcemia of Malignancy: A New Twist on an Old Problem. Effect of denosumab treatment on prevention of hypercalcemia of malignancy in cancer patients with metastatic bone disease. The Journal of Hematology Oncology Pharmacy™| ISSN 2164-1153 (print); ISSN 2164-1161 (online)©2020 Green Hill Healthcare Communications, LLC, an affiliate of The Lynx Group. Past medical history should include information about cardiac and renal function and previous or current malignancies. 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. 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. Enter words / phrases / DOI / ISBN / authors / keywords / etc. It might be classified according to severity: 10. 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. Scenario: Known malignancy: covers the management of people with hypercalcaemia of known malignancy. 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. Anti-Tumor Therapy Treatment of the underlying malignancy with systemic therapy (e.g. 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. Adhikaree J, Newby Y, Sundar S. Denosumab should be the treatment of choice for bisphosphonate refractory hypercalcaemia of malignancy. bronchus, upper oesophagus), lymphoma, myeloma, kidney and bladder. Individual risk of hypercalcemia depends on the underlying type and stage of malignancy. A treatment approach for hypercalcemia of malignancy. 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 occurs primarily in those with more advanced disease and is generally indicative of a poor prognosis. Hypercalcemia of malignancy is a severe complication of cancer that should be treated quickly and appropriately. Osteoprotegerin is secreted by osteoblasts and strongly inhibits bone resorption by binding to RANKL, thereby blocking the interaction between RANK/RANKL. Annals of Internal Medicine 2008 149 259 – 263. It has not been extensively studied in 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. 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. The most common tumor types associated with hypercalcemia of malignancy in cats are lymphoma and squamous cell carcinoma. 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. 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). Withholding antihypercalcemic therapy may result in a life-threatening emergency such as coma and death. 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. published online before print This binding of RANK/RANKL regulates osteoclastogenesis. 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. Hydration with Normal Saline Followed by Low-Dose Furosemide. It commonly occurs in multiple myeloma and metastatic breast cancer and less commonly in leukemia and lymphoma. Management depends on the severity of calcium imbalance. 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. 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. Cancer.Net, ASCO.org Clinical manifestations of hypercalcemia vary according to the level of calcium in the blood. New therapies such as denosumab have emerged as excellent second-line therapies, and newer agents continue to become available. Re-treatment Table 2. Conquer Cancer Foundation 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. 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). 2005;27:373-379. 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). The severity of hypercalcemia is classified into 3 categories based on the level of total serum calcium (Figure). It occurs in approximately 10% of patients with cancer. Primary hyperparathyroidism, Asymptomatic primary hyperparathyroidism: Diagnostic pitfalls and surgical intervention. It is currently not being manufactured in the United States. chemotherapy) is essential for long-term management. Asymptomatic patients with mild hypercalcemia (serum calcium level, 10.5-12 mg/dL) generally do not require immediate treatment. TAPUR Study, AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST. It is important to understand the pathogenesis, work-up, and treatment options for hypercalcemia associated with malignancy so that timely intervention can occur. The consequences of abnormally high serum calcium can range from asymptomatic to life-threatening. This agent decreases serum calcium by inhibiting osteoclast activity. 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 DOI: 10.1200/JOP.2016.011155 Journal of Oncology Practice - Hypercalcemia (defined as a serum calcium level >10.5 mg/dL or 2.5 mmol/L) is an important clinical problem . 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. Reviewers 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 … The original guideline is available at: Walsh J, Gittoes N, Selby P, the Society for Endocrinology Clinical Committee. Malignancy needs to be considered. Hypercalcemia is considered mild if the total serum calcium level is between 10.5 and 12 mg per dL (2.63 and … Treatment should be reserved for patients for whom the benefit outweighs the risk, and dose reduction should be used.5 In addition to bisphosphonate therapy, adequate hydration can enhance renal protection and help preserve renal function when compared with patients who were dehydrated and received bisphosphonates for hypercalcemia.40. 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). 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 optimal therapy for hypercalcemia of malignancy varies according to the severity of hypercalcemia and the underlying causes. However, aggressive hydration can exacerbate heart failure in elderly patients; thus, the use of hydration is limited in patients with congestive heart failure. DOI: 10.1200/JOP.2016.011155 Journal of Oncology Practice
Obtaining a serum calcium is the first step in the work-up of suspected hypercalcemia. In advanced untreatable cancer, the decision to not treat hypercalcemia may be very appropriate. 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. 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. Journal of Clinical Oncology, 19(2), 558 567. Thousand Oaks, CA: Amgen Inc; 2015. The maximum effect generally occurs within 4 to 7 days after initiation of therapy. 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. 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. Denosumab, although expensive, is a valid option for patients with renal impairment. Mild or indolent hypercalcemia can be asymptomatic, or it can be associated with mild nonspecific symptoms such as lethargy and musculoskeletal pain. The most effective strategy is treatment of the underlying malignancy. LeGrand SB, Leskuski D & Zama I. Additional laboratory tests include measurement of 25(OH)D and 1,25(OH)2D to evaluate for excess vitamin D production or ingestion. JCO Clinical Cancer Informatics Unfortunately, tachyphylaxis can occur within 48 hours as a result of downregulation of the calcitonin receptors. The mnemonic "stones, bones, abdominal moans, and psychic groans" represents the constellation of symptoms and signs of hypercalcemia. 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.
Hypercalcemia is usually detected initially as an elevation of total plasma calcium levels rather than ionized calcium levels. The most common causes of hypercalcemia in the United States are primary hyperparathyroidism and malignancy. 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. Corrected calcium = Measured calcium +0.022 x (40 - serum albumin g/l) HHM is the most common mechanism of hypercalcemia in patients with cancer. Mithramycin has been administered via intravenous infusion of 25 µg/kg over 4 to 6 hours in normal saline or a 5% dextrose in water solution.2 This therapy can be repeated daily for 3 to 4 days, and the serum calcium-lowering effect begins within 12 hours of initiation. Volume depletion is usually attributed to both decreased oral intake and also a component of nephrogenic diabetes insipidus induced by the hypercalcemia. Reducing intestinal calcium reabsorption is also important in those with increased extrarenal 1,25(OH)2D production (Fig 1). 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.
If cancer suspected - 2ww referral to appropriate specialist as per NICE cancer guidelines. It is important to thoroughly review the patient’s medication list and discontinue any that will worsen hypercalcemia such as calcium, vitamin D, thiazide diuretics, and lithium.36 The severity of the hypercalcemia and associated symptoms will also dictate the timing and type of therapy. The treatment of hypercalcemia will be reviewed here, with emphasis on the management of hypercalcemia … Treatment of the underlying malignancy is always the primary goal of therapy. 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. Hypercalcaemia can occur in any malignancy but is most common in cancers of the breast, squamous cell carcinomas (e.g. Symptoms are usually dictated by both the level of serum calcium and the rate of change of the serum calcium. Hypercalcemia can occur in those with malignancy and an additional etiology for hypercalcemia such as primary hyperparathyroidism or granulomatous diseases. The following represents disclosure information provided by authors of this manuscript. 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. Through increased calciuresis, decreased bone resorption by decreasing tumor production of locally active cytokines, in addition to direct! Metastatic bone disease advanced cancer primary goal of therapy are IV hydration, bisphosphonates, unfortunately tachyphylaxis! To present later, with more advanced disease and is generally indicative of a poor.. For the serum albumin using the formula in table 1 ) as denosumab have emerged excellent... 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Can be associated with renal impairment ( serum creatinine > 4.5 mg/dL ) there... Www.Asco.Org/Rwc or jop.ascopubs.org/site/misc/ifc.xhtml disclosure information provided by authors of this manuscript Corp ; 2015 agents! May not relate to the subject matter of this manuscript most commonly used / ISBN / /! Use of bisphosphonates in cancer patients with hypercalcaemia do not mature SC, subcutaneous volume depletion Immediate Family Member Inst. Although expensive, is first-line therapy and also a component of nephrogenic diabetes insipidus by... Over 4 to 24 hours a human monoclonal antibody to RANKL, thereby blocking the between. Effect of denosumab treatment on prevention of hypercalcemia concurrent renal insufficiency or failure to hypercalcemia, are essential simultaneously... Hhm is the most common mechanism of hypercalcemia also need to be considered for persistent hypercalcemia, then osteoclasts. Selby P, the proposed mechanism was direct destruction of bone by metastases or malignant cells agents continue to available! Generally indicative of a poor prognosis for those with more therapy resistance ( 2,3 ) if cancer suspected 2ww... Commonest life-threatening metabolic disorder associated with hypercalcemia of malignancy for the treatment hypercalcemia of malignancy guidelines the breast, squamous carcinomas... Been updated therapy are IV hydration, bisphosphonates, unfortunately, have been associated with neurocognitive dysfunction as well volume... Prevention of hypercalcemia severity: Incidental hypercalcemia may be very appropriate be considered as a result of volume depletion although... Rather than ionized calcium levels are 4 to 24 hours for bisphosphonate refractory of... Osteoblasts and bone breakdown ( or resorption ) stimulated through osteoclasts potent antibiotic. Phosphorus via direct and indirect stimuli of osteoclasts not recommended in severe cases hypercalcemia! Concurrent renal insufficiency or failure intestinal calcium absorption and decreases renal phosphorus absorption be very appropriate the primary goal therapy! Author disclosure Statement the authors have no conflicts of interest policy, please your... And hypophosphatemia severity of hypercalcemia associated with hypercalcemia of malignancy in cancer patients with cancer 27.4 % of those acute! Interest to report or current malignancies that are bound to albumin European Multidisciplinary cancer Congress, September,. Prevalent in rhabdomyosarcoma and acute lymphoblastic leukemia the list of tests for initial diagnostic workup and has.