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Hypercalcemia of Malignancy


Presentation

  • We present a case report of a severe hypercalcemia due to a rare association and review the relevant literature.[ncbi.nlm.nih.gov]
  • One patient presented with concomitant elevation of PTHrP and intact parathyroid hormone (PTH) in the setting of multiple endocrine neoplasia 1 (MEN1). In all the other cases, PTH levels were low or undetectable.[ncbi.nlm.nih.gov]
  • Abstract A 60-year-old woman presented with hypercalcemia and was found to have metastatic pancreatic islet cell carcinoma.[ncbi.nlm.nih.gov]
  • Author information 1 Department of Internal Medicine, Baylor University Medical Center, Dallas, TX 75246, USA. [email protected] Abstract A 65-year-old Caucasian woman with a known history of clear cell endometrial cancer presented with hypercalcemia.[ncbi.nlm.nih.gov]
  • Abstract We report the case of a 63-year-old man who presented with weakness, fatigue, dehydration, confusion, abdominal pain, congestive heart failure and hypercalcemia.[ncbi.nlm.nih.gov]
Fatigue
  • Abstract We report the case of a 63-year-old man who presented with weakness, fatigue, dehydration, confusion, abdominal pain, congestive heart failure and hypercalcemia.[ncbi.nlm.nih.gov]
  • Patients with mild hypercalcemia (serum calcium 10.5-12 mg/dL) can present with constipation, fatigue, and depression.[advancedpractitioner.com]
  • The most common ( 10%) symptoms at baseline were fatigue, anorexia, nausea, lethargy, and constipation.[academic.oup.com]
  • Most commonly reported adverse reactions are renal toxicity, flu-like symptoms, injection site reactions, hypocalcemia, hypophosphatemia, fatigue, muscle weakness, and constipation of diarrhea.[oatext.com]
  • But the first signs might be: extreme tiredness (fatigue) and lethargy feeling weak not wanting to eat much constipation loss of concentration and interest in doing things mild confusion Untreated high calcium symptoms Untreated high calcium symptoms[cancerresearchuk.org]
Ascitic Fluid
  • Increased levels of PTHrP were present both in the serum (4.9 pmol/l; normal for adults 1.5) and ascitic fluid (6.1 pmol/l).[ncbi.nlm.nih.gov]
Nausea
  • The most common ( 10%) symptoms at baseline were fatigue, anorexia, nausea, lethargy, and constipation.[academic.oup.com]
  • However, mithramycin is not commonly recommended in hypercalcemia associated with malignancy due to dose-related adverse effects including nausea, vomiting, stomatitis, thrombocytopenia, and renal and hepatotoxicity.[oatext.com]
  • Typical symptoms include nausea, vomiting, constipation, abdominal pain, anorexia, weight loss, bone pain, polyuria, fatigue, and weakness.[cjasn.asnjournals.org]
  • Dehydration caused by nausea and vomiting makes it hard for the kidneys to remove calcium from the blood properly. Lack of physical activity can cause bone to break down, releasing calcium into the blood.[cancer.net]
  • Complicating diagnosis, the same symptoms common to advanced cancer are also seen in hypercalcemia of malignancy: nausea, constipation, anorexia, malaise and fatigue.[acphospitalist.org]
Abdominal Pain
  • Abstract We report the case of a 63-year-old man who presented with weakness, fatigue, dehydration, confusion, abdominal pain, congestive heart failure and hypercalcemia.[ncbi.nlm.nih.gov]
  • A 72-year-old Japanese man was admitted to our institution complaining of fever and abdominal pain. Abdominal computed tomography demonstrated a large tumor in the body of the pancreas, with multiple liver metastases.[ncbi.nlm.nih.gov]
  • Complete Peer review History: Abstracts Hypercalcemia in malignancy can present with metabolic derangement, generalized weakness, altered mental status, renal compromise, cardiac dysrhythmias including atrial fibrillation and bradycardia, abdominal pain[sciencedomain.org]
  • Case A 63-year-old man with hypertension, diabetes, and recently diagnosed squamous-cell lung cancer presents with diffuse abdominal pain and confusion of two-day duration.[the-hospitalist.org]
  • People with hypercalcemia may have the following symptoms: Loss of appetite Nausea and vomiting Constipation and abdominal pain Increased thirst and frequent urination Fatigue, weakness, and muscle pain Confusion, disorientation, and difficulty thinking[cancer.net]
Vomiting
  • However, mithramycin is not commonly recommended in hypercalcemia associated with malignancy due to dose-related adverse effects including nausea, vomiting, stomatitis, thrombocytopenia, and renal and hepatotoxicity.[oatext.com]
  • Typical symptoms include nausea, vomiting, constipation, abdominal pain, anorexia, weight loss, bone pain, polyuria, fatigue, and weakness.[cjasn.asnjournals.org]
  • Symptoms include nausea, vomiting, abdominal pain, bone pain, fatigue, and confusion. Ultimately, HCM can result in renal failure, coma, and death, with an estimated 50% survival of 30 days regardless of treatment ( 4 ).[academic.oup.com]
  • This can be managed by: Treating the cancer Replacing fluids lost through vomiting, frequent urination, or other reasons Taking medicines to help stop the breakdown of bone.[cancer.net]
  • Symptoms of hypercalcemia include: nausea vomiting loss of appetite, or anorexia constipation fatigue muscle weakness increased thirst frequent and increased urination dark yellow urine little or no sweating abnormal heart rhythm weaker muscle reflexes[cancer.ca]
Loss of Appetite
  • People with hypercalcemia may have the following symptoms: Loss of appetite Nausea and vomiting Constipation and abdominal pain Increased thirst and frequent urination Fatigue, weakness, and muscle pain Confusion, disorientation, and difficulty thinking[cancer.net]
  • Symptoms of hypercalcemia include: nausea vomiting loss of appetite, or anorexia constipation fatigue muscle weakness increased thirst frequent and increased urination dark yellow urine little or no sweating abnormal heart rhythm weaker muscle reflexes[cancer.ca]
Bone Pain
  • In addition to improving the morbidity of acute hypercalcemia, bisphosphonate therapy has been shown to reduce bone pain and pathological fractures in patients with bone metastases, and calcitonin also has a potent analgesic effect in these patients.[ncbi.nlm.nih.gov]
  • Abstract Bisphosphonates have become standard treatment in management of malignancy-induced hypercalcemia and malignant bone pain.[ncbi.nlm.nih.gov]
  • pain and weakness irregular heart beat difficulty thinking and speaking clearly It might also lead to coma and eventually death if not treated.[cancerresearchuk.org]
  • pain or bone fracture Report symptoms to your doctor or healthcare team as soon as possible.[cancer.ca]
  • Other symptoms include bone pain, arthritis, and osteoporosis. [2].[oatext.com]
Muscle Weakness
  • Those with moderate hypercalcemia (12 to 14 mg/d) can develop polydipsia, polyuria, clinical dehydration, muscle weakness, and changes in mental status. Those with severe hypercalcemia can develop severe form of these symptoms.[advancedpractitioner.com]
  • Most commonly reported adverse reactions are renal toxicity, flu-like symptoms, injection site reactions, hypocalcemia, hypophosphatemia, fatigue, muscle weakness, and constipation of diarrhea.[oatext.com]
  • Symptoms of hypercalcemia include: nausea vomiting loss of appetite, or anorexia constipation fatigue muscle weakness increased thirst frequent and increased urination dark yellow urine little or no sweating abnormal heart rhythm weaker muscle reflexes[cancer.ca]
  • Abnormally high level of calcium in the blood; manifestations include fatigability, muscle weakness, depression, anorexia, nausea, and constipation. High level of calcium in the blood Higher than normal levels of calcium in the blood.[icd10data.com]
  • Presentation of Hypercalcaemia At levels At levels At levels 3.5 mmol/L Polyuria and polydipsia Dyspepsia - due to calcium-regulated release of gastrin Depression Mild cognitive impairment All of the previous plus: Muscle weakness Constipation Anorexia[patient.info]
Polyuria
  • Those with moderate hypercalcemia (12 to 14 mg/d) can develop polydipsia, polyuria, clinical dehydration, muscle weakness, and changes in mental status. Those with severe hypercalcemia can develop severe form of these symptoms.[advancedpractitioner.com]
  • A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med 1981; 305: 1539-46. ‎[books.google.ro]
  • Since some tumor cells can resorb or destroy bone directly, hypercalcemia develops more rapidly and more aggressively than other causes of hypercalcemia, along with classic symptoms of dehydration, anorexia, nausea/vomiting, constipation, and polyuria[oatext.com]
  • Typical symptoms include nausea, vomiting, constipation, abdominal pain, anorexia, weight loss, bone pain, polyuria, fatigue, and weakness.[cjasn.asnjournals.org]
  • The administration of both has been shown to cause a metabolic alkalosis and hypokalemia with polyuria.[karger.com]
Nocturia
  • The clinical manifestations of hypercalcemia include: Central nervous system effects include lethargy, impaired concentration, fatigue, and muscle weakness; Renal effects include dehydration, polyuria, nocturia, nephrolithiasis resulting from hypercalciuria[oatext.com]
Altered Mental Status
  • Complete Peer review History: Abstracts Hypercalcemia in malignancy can present with metabolic derangement, generalized weakness, altered mental status, renal compromise, cardiac dysrhythmias including atrial fibrillation and bradycardia, abdominal pain[sciencedomain.org]
  • Patients receiving gallium have reported nausea, vomiting, lethargy, altered mental status, and both diarrhea and constipation. Calcitonin Calcitonin is a peptide hormone secreted by the parafollicular C cells of the thyroid gland.[cjasn.asnjournals.org]

Workup

  • A thorough workup ruled out bone metastasis and confirmed increased parathyroid-related protein, the hallmark of HHM. After regaining consciousness, the patient refused further therapy and subsequently died.[ncbi.nlm.nih.gov]
  • Further workup for the etiology of his hypercalcemia revealed an appropriately suppressed, intact PTH and normal 25 (OH) Vitamin D and 1,25 (OH)2 Vitamin D levels.[the-hospitalist.org]
  • Diagnostic workup of patients with suspected hypercalcemia of malignancy Diagnostic workup of patients with hypercalcemia of unknown origin Hypercalcemia of malignancy is a common cause of hypercalcemia in hospitalized patients.[mayomedicallaboratories.com]
  • Approximately 50% of calcium is bound to protein, primarily albumin, and the remaining 50% is ionized and is in physiologic active form. [5] Workup When calcium levels are reported as abnormal, the first step is to measure the albumin level.[emedicine.medscape.com]
  • The workup to elucidate the etiology of his hypercalcemia revealed his intact PTH level to be appropriately suppressed to 0.95 pmol/l (normal range: 1.06-6.9 pmol/l) and his PTH-related peptide level to be 27 ng/l (normal range: 14-27 ng/l). 25-hydroxy[karger.com]
Liver Biopsy
  • Computed tomography scan and liver biopsy revealed recurrent transitional-cell carcinoma with extensive liver metastasis. The patient returned approximately 1 week after discharge with a serum calcium level of 13.9 mg/dL.[ncbi.nlm.nih.gov]

Treatment

  • Abstract Treatment of hypercalcemia of malignancy (HCM) is briefly reviewed, available treatments are compared, and treatment guidelines are presented. The most effective strategy is treatment of the underlying malignancy.[ncbi.nlm.nih.gov]
  • Knowledge of the rationales for the various treatment modalities will assist nurses in implementing antihypercalcemic treatments, evaluating treatment effectiveness and side effects, instituting pain management programs, and providing comfort measures[ncbi.nlm.nih.gov]
  • Multiple treatment modalities exist for the treatment of hypercalcemia, each with a different mechanism of action.[ncbi.nlm.nih.gov]
  • The experimental intravenous dosage is 2 mg every 3 months for treatment or prevention of osteoporosis, and 2-6 mg every 3-4 weeks or in a single dose for treatment of bone metastases or hypercalcemia of malignancy, respectively.[ncbi.nlm.nih.gov]
  • Twelve patients (6 in each treatment group) had confirmed skeletal metastases.[ncbi.nlm.nih.gov]

Prognosis

  • CONCLUSIONS: The plasma PTH-rp levels may help to predict the calcium-lowering effect of bisphosphonate and give an indication of the prognosis in patients with HM.[ncbi.nlm.nih.gov]
  • The development of this malignancy complication often purports a poor prognosis. Thorough evaluation to establish the cause of hypercalcemia is essential because some patients may actually have undiagnosed primary hyperparathyroidism.[ncbi.nlm.nih.gov]
  • For patients who have a poor prognosis and no viable treatment options, the most humane course may be no treatment at all since encephalopathy will cloud their consciousness.[ncbi.nlm.nih.gov]
  • In general, hypercalcemia of malignancy portends a poor prognosis, and there are three main mechanisms by which hypercalcemia can occur: 1.[renalfellow.blogspot.com]

Etiology

  • Abstract The etiology, pathophysiology, and diagnosis of hypercalcemia associated with malignant diseases are discussed.[ncbi.nlm.nih.gov]
  • No etiology could be determined for 98 cases of MAHC (40%) and increased PTHrP contributed to 92 cases (38%) of MAHC. Age, race and gender were not associated with HHM. Increased PTHrP was observed at initial malignancy diagnosis in 20% of cases.[ncbi.nlm.nih.gov]
  • Besides the etiology related to the malignancy, other causes should be considered in the differential diagnostic, as primary hyperparathyroidism, granulomatous diseases and the use of thiazide diuretics.[ncbi.nlm.nih.gov]
  • To investigate the etiology of this form of HHM we have characterized expression and activity of the enzyme that catalyzes synthesis of 1,25(OH)2D3, 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase), in a collection of 12 dysgerminomas.[ncbi.nlm.nih.gov]
  • More broadly, the poster will include an overview of the presentation, etiology, therapeutic options, and practical considerations in managing this important oncologic syndrome.[advancedpractitioner.com]

Epidemiology

  • […] and Gynecology , Columbia University , New York , USA. 2 b Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons , Columbia University , New York , USA. 3 c New York Presbyterian Hospital , New York , USA. 4 d Department of Epidemiology[ncbi.nlm.nih.gov]
  • Summary Epidemiology Prevalence is unknown.[orpha.net]
  • Epidemiology and etiology The most common causes of hypercalcemia in the United States are primary hyperthyroidism and malignancy.[oatext.com]
  • Epidemiology Hypercalcaemia is an uncommon problem. Primary hyperparathyroidism is the most common cause. It affects mainly postmenopausal women [ 5 ] . The incidence rate in the UK is 30 per 100,000 [ 6 ] .[patient.info]
Sex distribution
Age distribution

Pathophysiology

  • Abstract The etiology, pathophysiology, and diagnosis of hypercalcemia associated with malignant diseases are discussed.[ncbi.nlm.nih.gov]
  • The pathophysiological mechanisms of hypercalcemia appear to be a determinant of the efficacy of different antihypercalcemic treatments.[ncbi.nlm.nih.gov]
  • Recent insights into the pathophysiology of HCM include an understanding of the role of parathyroid-hormone-related peptide and several cytokines secreted by tumors.[ncbi.nlm.nih.gov]
  • Oncology nurses must have an understanding of which malignancies pose increased risk and how pathophysiologic mechanisms precipitate or contribute to hypercalcemia of malignancy.[ncbi.nlm.nih.gov]
  • However, CaR function can be aberrant in certain pathophysiological states, e.g., in some types of cancers known to produce humoral hypercalcemia of malignancy (HHM) in humans and animal models in which high Ca2 (o), via the CaR, produces a homeostatically[ncbi.nlm.nih.gov]

Prevention

  • Abstract Ibandronate is an experimental intravenous bisphosphonate under study for the prevention or treatment of osteoporosis and skeletal complications of bone metastases, as well as hypercalcemia of malignancy.[ncbi.nlm.nih.gov]
  • BACKGROUND: Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with[ncbi.nlm.nih.gov]
  • Co-administration of oral calcium supplement of 500 mg and multiple vitamins containing 400 IU of vitamin D are recommended to prevent hypercalcemia [4-7].[oatext.com]
  • Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012;48:3082-3092 Recommended Citation Milhem, Maali M.[mds.marshall.edu]
  • […] which PTHrP secreted by s.c. xenografts of human lung cancer in nude mice induces extensive osteolysis and severe hypercalcemia, daily administration of muRANK.Fc from time of tumor implantation profoundly inhibited osteoclastic bone resorption and prevented[ncbi.nlm.nih.gov]

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