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Hypercalcemia complicates the course of 10%-30% of all patients with malignancies and can be a sign of very poor prognosis and advanced malignancy. Prompt recognition of the nonspecific signs and symptoms of hypercalcemia and institution of therapy can be lifesaving, affording the opportunity to address the underlying etiology. The mechanisms of ma...
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Context:
Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy.
Objective:
We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in...
Objective: To report a case of hypercalcemic crisis in an African-American male who presented with a non-healing ulcer which was later found to be squamous cell carcinoma.
Methods: All relevant data, radiological imaging and pathology reports were reviewed in detail. An in-depth literature review for humoral hypercalcemia of malignancy and cutaneou...
Management of humoral hypercalcaemia of malignancy (HHM) refractory to bisphosphonates, or where their use is contraindicated, can be challenging. We present a case of PTHrP-secreting metastatic pancreatic neuroendocrine tumour (NET) with recurrent hypercalcaemic crises and renal failure. The challenges of managing hypercalcaemia in the presence of...
Hypercalcemia is an ominous development in the course of malignancy associated with a mean survival of only several months. A majority of cases of hypercalcemia are related to humoral hypercalcemia of malignancy (HHM), where hypercalcemia is caused by increased levels of circulating parathyroid hormone-related protein (PTHrP). Mainstay treatments i...
Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast ca...
Citations
... Because the majority of the calcium pool is stored in bones, tumor bone metastases formation including processes of enhanced bone resorption and osteolytic lesions formation, can lead to the release of excessive amounts of calcium into the bloodstream [16]. The following deregulation of calcium homeostasis entails multiple clinical manifestations as it affects the functionality of numerous organs and systems, from gastrointestinal or muscular to the nervous system in the case of more severe hypercalcemia, and its symptoms can range from mild to even occasionally life-threatening [17]. ...
Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as cancer, and as a result, hyper- or hypocalcemia can occur. These states, characterized by elevated or decreased calcium blood levels, respectively, have a significant effect on general homeostasis. This article focuses on a particular form of calcium metabolism disorder, which is hypercalcemia in neoplasms. It also constitutes a summary of the current knowledge regarding the diagnosis of hypercalcemia and its management. Hypercalcemia of malignancy is estimated to affect over 40% of cancer patients and can be associated with both solid and blood cancers. Elevated calcium levels can be an indicator of developing cancer. The main mechanism of hypercalcemia development in tumors appears to be excessive production of parathyroid hormone-related peptides. Among the known treatment methods, bisphosphonates, calcitonin, steroids, and denosumab should be mentioned, but ongoing research promotes progress in pharmacotherapy. Given the rising global cancer prevalence, the problem of hypercalcemia is of high importance and requires attention.
... [21]. Hypercalcemia may independently cause nephrocalcinosis which may further worsen electrolyte and acid-base complications [22,23]. Our observation of higher odds of acute encephalopathy reflects the impact of several factors including the effect of primary lymphoma, central nervous system (CNS) involvement, CNS paraneoplastic syndrome, the effect of hypercalcemia and metabolic encephalopathy due to electrolyte derangement, acid-base disorders, and uremia, as well as hypercalcemia related posterior reversible encephalopathy syndrome. ...
Introduction
Diffuse large B-cell lymphoma (DLBCL) may be complicated by hypercalcemia at various stages of treatment. The impact of hypercalcemia on chemotherapy admission outcomes in DLBCL is not well described.
Methods
In a retrospective analysis, using the National Inpatient Sample database (2018 - 2020), patients with DLBCL admitted for chemotherapy were dichotomized based on the presence of hypercalcemia. Our primary outcome was all-cause mortality. Secondary outcomes included length of stay (LOS), total charge, rate of acute kidney injury (AKI), tumor lysis syndrome (TLS), hyperkalemia, metabolic acidosis, acute encephalopathy, septic shock, Clostridiodes difficile infection, acute respiratory failure, and venous thromboembolic events (VTE).
Results
We identified 78,955 patients, among whom 1,375 (1.74%) had hypercalcemia. Hypercalcemia was associated with higher odds of all-cause mortality (aOR:3.05, p-value:0.020), TLS (aOR:8.81, p-value<0.001), acute metabolic encephalopathy (aOR:4.89, p-value<0.001), AKI (aOR:5.29, p-value<0.001), hyperkalemia (aOR:2.84, p-value:0.002), metabolic acidosis (aOR:3.94, p-value<0.001) and respiratory failure (aOR:2.29, p-value:0.007) and increased LOS by 1 day and total charge by 12, 501 USD.
Conclusions
In patients with DLBCL admitted for inpatient chemotherapy, those with hypercalcemia compared to a cohort without had higher odds of; all-cause mortality, TLS, AKI, acute encephalopathy, acute metabolic acidosis, hyperkalemia, and acute respiratory failure as well as higher LOS and total charge.
... A vicious circle between hypercalcemia and decreased kidney function causes this. Hypercalcemia leads to decreased kidney function through a combination of natriuretic effects followed by hypovolemia and renal vasoconstriction [10,11]. Decreased kidney function limits the ability of the kidneys to excrete calcium, leading to persistent hypercalcemia. ...
Teriparatide, a recombinant human parathyroid hormone, is an anabolic treatment for osteoporosis with a high risk of fractures. Transient hypercalcemia is an adverse effect of teriparatide and usually resolves within 16h of teriparatide administration owing to its rapid absorption and elimination. Some cases of prolonged hypercalcemia have been reported, but these improved rapidly after teriparatide discontinuation. Here, we describe a rare case of teriparatide-induced hypercalcemia concomitant with acute kidney injury that persisted for four weeks. An 83-year-old woman began taking teriparatide for a vertebral fracture. The patient was immobilized by the fracture. Three weeks later, the patient developed hypercalcemia and acute kidney injury. However, hypercalcemia persisted for four weeks despite the discontinuation of teriparatide and fluid administration. Clinicians should be aware that teriparatide can induce severe hypercalcemia, especially in the setting of immobilization, and that hypercalcemia can persist for more than 3-4 weeks in patients with decreased kidney function.
... [2][3][4][5] Severe hypercalcemia secondarily causes renal impairment by 4 mechanisms: decreased blood flow and glomerular filtration rate (GFR) secondary to vasoconstriction, impaired anti-diuretic hormone (ADH) response, renal tubular damage caused by impaired calcium clearance, and volume depletion leading to tubular injury. 6 Although unknown in the canine population, the incidence of HM is reported to be 10% to 30% in humans, 1,3 increasing dramatically with cancer progression. 1 Various cancers are associated with HM in humans, 1,7 whereas in dogs, the principal cancers involved include lymphoma 8 and anal sac apocrine gland adenocarcinoma, although others also have been reported. 2,9 In humans and dogs, HM reportedly carries a poor prognosis, resulting in substantial morbidity at the onset of disease secondary to its clinical complications, but, a recent study evaluating dogs with high-grade primary mediastinal lymphoma did not find HM to be a prognostic indicator for outcome. ...
... to the effect of PTHrP on the response of collecting tubules to ADH and subsequent volume depletion, the direct toxic effect of calcium on the renal tubules, pre-renal factors affecting GFR, and further decrease in GFR and vasoconstriction secondary to low parathyroid hormone concentration. 6,22 In humans, sustained hypercalcemia causing renal impairment can be mild and reversible with appropriate treatment and resolution of hypercalcemia or more severe and permanent, leading to marked renal damage. 22 Despite literature to support the development of hypercalcemic nephropathy in dogs with underlying neoplasia, the prevalence and outcomes, especially in dogs with lymphoma have not been well described. ...
Background
Hypercalcemia of malignancy (HM) secondary to lymphoma in dogs has the potential to cause renal injury.
Hypothesis/Objectives
Characterize outcomes related to acute kidney injury (AKI) secondary to HM. We hypothesized that dogs do suffer AKI regardless of HM severity at the time of lymphoma diagnosis or relapse.
Animals
Retrospective study. Twenty‐nine dogs with lymphoma, HM, and azotemia (International Renal Interest Society [IRIS] grade II or higher AKI) that underwent chemotherapy were identified at 2 veterinary institutions.
Methods
Logistic regression and descriptive statistical analysis were performed to evaluate data for potential prognostic factors.
Results
After initiating treatment, resolution of hypercalcemia and azotemia occurred in 100% (29/29) and 79.3% (23/29) of dogs, respectively. Resolution of azotemia was influenced by serum creatinine concentration (odds ratio [OR], 0.148; Confidence interval [CI], 0.03‐0.734; P = .02) and total hypercalcemia (OR, 0.36; CI, 0.14‐0.93; P = .04) at diagnosis, whereas blood urea nitrogen concentration, IRIS grade, sex, and whether or not dogs were hospitalized were not significant factors. At data analysis, 13.8% (4/29) of dogs were alive or lost to follow‐up. Of those dead, 4 dogs (15%) had renal disease at the time of death, 2/4 having concurrent lymphoma progression.
Conclusions and Clinical Importance
Although AKI may be of clinical concern in dogs with HM secondary to lymphoma at diagnosis, death secondary to renal impairment appears to be infrequent.
... Cardiovascular and neurologic complaints occur especially with a calcium level higher than 14 mg/ dl. On the other hand, it may have a gradual course and nonspecific presentation, causing delay in diagnosis [6]. ...
Background
Hypercalcemia of malignancy, as a paraneoplastic syndrome, is the most common metabolic disorder that accounts for 30% of malignancies and usually has a poor prognosis. Neuroendocrine tumors are uncommon and arise from neuroendocrine cells throughout the body. Actually, paraneoplastic hypercalcemia in neuroendocrine tumors is unusual and mostly associated with parathyroid hormone-related protein (PTHrP) secretion.
Case presentation
We report a 51-year-old Iranian man who presented with nausea, vomiting, and significant weight loss for 1 month. Laboratory data revealed calcium of 26 mg/dl, accompanied by low level of PTH. Octreotide scan revealed a large donut-shaped octreotide avid lesion in the epigastric region at the right side of the mid-abdomen, with multiple varying size foci of abnormally increased radiotracer uptake in the epigastric region and both lobes of the liver. Endoscopic ultrasonography demonstrated a large heterogeneous mass lesion with irregular outline and good demarcation in the body of the pancreas with diffuse foci of calcification. Percutaneous biopsy of the liver mass demonstrated a well-differentiated neuroendocrine tumor (low grade) confirmed by immunohistochemistry with strongly positive chromogranin and synaptophysin stain. Hypercalcemia was treated with hydration, few sessions of hemodialysis, calcitonin, and denosumab injection. However, the patient developed symptomatic hypocalcemia. Oncology consultation led to prescription of long-acting octreotide 30 mg monthly and everolimus daily.
Conclusion
Pancreatic neuroendocrine tumor could lead to malignant hypercalcemia; secretion of PTHrP is the most common cause, and signs and symptoms are usually milder than paraneoplastic syndrome due to hematologic and solid tumor. Generally, survival is better; however, its treatment is challenging, and primary debulking surgery is often required. A team approach to management is important at all points.
... The treatment is based on the antineoplastic therapy of the underlying disease, and other measures must be taken in relation to the clinical condition. In patients with few symptoms, the use of AVP-receptor antagonists can be considered, while in patients with severe symptoms, a hypertonic solution remains the treatment of choice [66][67][68]. ...
Citation: Gri, N.; Longhitano, Y.; Zanza, C.; Monticone, V.; Fuschi, D.; Piccioni, A.; Bellou, A.; Esposito, C.; Ceresa, I.F.; Savioli, G. Acute Oncologic Complications: Clinical-Therapeutic Management in Critical Care and Emergency Departments. Curr. Oncol. 2023, 30, 7315-7334. https://doi. Abstract: Introduction. It is now known that cancer is a major public health problem; on the other hand, it is less known, or rather, often underestimated, that a significant percentage of cancer patients will experience a cancer-related emergency. These conditions, depending on the severity, may require treatment in intensive care or in the emergency departments. In addition, it is not uncommon for a tumor pathology to manifest itself directly, in the first instance, with a related emergency. The emergency unit proves to be a fundamental and central unit in the management of cancer patients. Many cancer cases are diagnosed in the first instance as a result of symptoms that lead the patient's admittance into the emergency room. Materials and Methods. This narrative review aims to analyze the impact of acute oncological cases in the emergency setting and the role of the emergency physician in their management. A search was conducted over the period January 1981-April 2023 using the main scientific platforms, including PubMed, Scopus, Medline, Embase and Google scholar, and 156 papers were analyzed. Results. To probe into the main oncological emergencies and their management in increasingly overcrowded emergency departments, we analyzed the following acute pathologies: neurological emergencies, metabolic and endocrinological emergencies, vascular emergencies, malignant effusions, neutropenic fever and anemia. Discussion/Conclusions. Our analysis found that a redefinition of the emergency department connected with the treatment of oncology patients is necessary, considering not only the treatment of the oncological disease in the strict sense, but also the comorbidities, the oncological emergencies and the palliative care setting. The need to redesign an emergency department that is able to manage acute oncological cases and end of life appears clear, especially when this turns out to be related to severe effects that cannot be managed at home with integrated home care. In conclusion, a redefinition of the paradigm appears mandatory, such as the integration between the various specialists belonging to oncological medicine and the emergency department. Therefore, our work aims to provide what can be a handbook to detect, diagnose and treat oncological emergencies, hoping for patient management in a multidisciplinary perspective, which could also lead to the regular presence of an oncologist in the emergency room. Curr. Oncol. 2023, 30, 7315-7334. https://doi.org/10.3390/curroncol30080531 https://www.mdpi.com/journal/curroncol Curr. Oncol. 2023, 30 7316
... The treatment of hypercalcemic crisis in diffuse large B-cell lymphoma consists of four basic principles: ① Correction of volume deficit: The initial rate and duration of rehydration should be determined according to the clinical symptoms of dehydration, the duration and severity of hypercalcemia, and the patient's underlying disease, especially the presence of cardiac insufficiency. After achieving an adequate rehydration status, a tab diuretic (e.g., tachyphylaxis) may be added as appropriate, but care should be taken to monitor central venous pressure and assess systemic status to avoid serious electrolyte disturbances from the use of diuretics [12].②Inhibit bone resorption: Calcitonin can inhibit osteoclast activity as well as renal tubular reabsorption of calcium and phosphorus, with rapid action, and can rapidly reduce blood calcium concentration; zoledronate and pamidronate can also inhibit osteoclast activity. ...
Hypercalcaemia associated with malignancy is a complication of advanced tumors. Lactic acidosis is also an extremely rare paraneoplastic syndrome of malignancy, and the presence of both usually indicates an extremely poor prognosis for the tumour. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma and is also a common aggressive lymphoma. It is extremely rare for patients with diffuse large B-cell lymphoma to develop both hypercalcaemia and severe lactic acidosis. In this article, we report a case of CD5 positive diffuse large B-cell lymphoma with hypercalcaemic crisis and persistent lactic acidosis, in which calcium was rapidly reduced to normal after rehydration, diuresis, calcitonin and zoledronate, and continuous renal replacement therapy (CRRT). After correction of acidosis with sodium bicarbonate, diuresis, vitamin B1 and CRRT, the patient's lactate remained at a high level. The aim of this article is to analyse the experience of the combination of hypercalcaemia and intractable lactic acidosis, which should be considered as a serious electrolyte disorder possibly associated with abnormal metabolism of malignant tumors, and to identify and treat the primary lesion as early as possible.
... Kannan et al presented a case of severe hypercalcemia in an immobilized patient recently diagnosed with COVID-19 [7]. The virus that causes COVID-19 has broad tropism and can affect different areas of the body, including the bones and kidneys [8]. COVID-19 can also affect the respiratory system and is known to cause severe respiratory failure and death [9]. ...
BACKGROUND Hypercalcemia, a serum calcium exceeding 10.5 mg/dL, is a multi-factorial metabolic disorder that results from an imbalance in calcium homeostasis. CASE REPORT We report a case of a 67-year-old male with recently diagnosed multiple myeloma who presented to our emergency department 3 weeks after COVID-19 infection with altered mental status and a fall. On admission he was found to have severe hypercalcemia with a level over 18.0 mg/dL. Despite IV fluids, calcitonin, steroids, and zoledronic acid, he had persistent, critically elevated calcium levels. The decision to initiate hemodialysis was made, which successfully treated his hypercalcemia. CONCLUSIONS This report presents a case of malignant hypercalcemia in an individual with COVID-19 and multiple myeloma and highlights the importance of considering dialysis as a viable treatment for hypercalcemia when other modalities have failed.
... Tumor-related hypercalcemia accounts for the majority of cases and is common in patients with multiple myeloma and advanced-stage cancer. The prognosis for patients with cancer-related hypercalcemia is poor, with a reported median survival of only 2-6 months [231,232]. Most often, it is caused by the release of parathyroid hormone-related protein (PTHrP) (80% of all cases) or by local osteolysis (20% of all cases). ...
The prevalence of CKD may be higher in patients with cancer than in those without due to the addition of cancer-specific risk factors to those already present for CKD. In this review, we describe the evaluation of kidney function in patients undergoing anticancer drug therapy. When anticancer drug therapy is administered, kidney function is evaluated to (1) set the dose of renally excretable drugs, (2) detect kidney disease associated with the cancer and its treatment, and (3) obtain baseline values for long-term monitoring. Owing to some requirements for use in clinical practice, a GFR estimation method such as the Cockcroft-Gault, MDRD, CKD-EPI, and the Japanese Society of Nephrology's GFR estimation formula has been developed that is simple, inexpensive, and provides rapid results. However, an important clinical question is whether they can be used as a method of GFR evaluation in patients with cancer. When designing a drug dosing regimen in consideration of kidney function, it is important to make a comprehensive judgment, recognizing that there are limitations regardless of which estimation formula is used or if GFR is directly measured. Although CTCAEs are commonly used as criteria for evaluating kidney disease-related adverse events that occur during anticancer drug therapy, a specialized approach using KDIGO criteria or other criteria is required when nephrologists intervene in treatment. Each drug is associated with the different disorders related to the kidney. And various risk factors for kidney disease associated with each anticancer drug therapy.
... Se inició manejo con soluciones cristaloides con cloruro de sodio al 0.9%, 1000 ml en 6 h, así como diurético de asa (furosemida 40 mg intravenoso cada 8 h) para forzar la diuresis, eliminación del calcio y mejorar la función renal. No se inició ninguna otra terapia, como bisfosfonatos, la reabsorción de sodio y cloro, así como la inactivación de los efectos de la arginina vasopresina, por lo que estos pacientes muestran una depleción profunda de volumen 13 . Una vez establecido el diagnóstico por laboratorio de hipercalcemia se debe realizar una determinación de la albúmina sérica, pues esta se ve relacionada de manera estrecha con el transporte de calcio en el plasma, y la disminución de la albúmina impacta de manera directa en el diagnóstico de la hipercalcemia, por lo que se debe tomar en cuenta la siguiente fórmula para su corrección: calcio real = calcio medido -0.8 (4.0 -albúmina medida) 5,9 . ...
