II. Epidemiology

  1. Incidence: 10-30% of cancer patients

III. Pathophysiology

  1. Paraneoplastic syndrome (most common, 80% of cases)
    1. Tumor secretes Parathyroid Hormone related peptide (PTHrP)
    2. Results in increased calcium reabsorption in Kidney
  2. Other mechanisms
    1. Bone Metastases release calcium
    2. Local osteolysis by cytokines
    3. Cancer may release circulating bone-resorbing cytokines, calcitriol (Vitamin D)
  3. Rare mechanisms
    1. Immobilization
    2. Medications
    3. Parathyroid carcinoma

IV. Causes: Primarily Breast, lung and Bone Cancers

V. Symptoms

VI. Labs

  1. Serum Calcium >10.5 mg/dl
    1. Adjust for albumin, as Malnutrition is common (obtain Ionized Calcium if available)

VII. Management

  1. See Hypercalcemia for other management
  2. Consult Oncology, Endocrinology, Nephrology
  3. Acute Management
    1. Initial Management (typically in emergency department)
      1. Aggressive rehydration (up to 4 liters Lactated Ringers or Normal Saline per 24 hours)
    2. Next Management (typically after admission)
      1. Furosemide 10-20 mg IV q6-12 hours after rehydration
    3. Acute Renal Failure Management
      1. Consider Dialysis
  4. Monitor serum electrolytes
    1. Serum Calcium (may start as high as 14 mg/dl)
  5. Hypophosphatemia specific management
    1. Indication for Phosphorus Replacement: Serum Phosphate <3 mg/dl
    2. Neutro-Phos 250 mg Phosphorous PO or NG daily
  6. Hypercalcemia specific management
    1. Indications
      1. Serum Calcium >14 mg/dl if asymptomatic
      2. Serum Calcium >12 mg/dl if symptomatic
    2. Methods
      1. Glucocorticoids
        1. Decrease intestinal calcium absorption
      2. Calcitonin
        1. Inhibits Osteoclasts
      3. Bisphosphonates
        1. Inhibit Osteoclast mediated bone resorption (delayed effect over days)
        2. Zoledronic acid: 4 mg IV over 15 min (preferred over Pamidronate)
        3. Pamidronate (Aredia) 60-90 mg IV q4 hours
        4. Major (2001) J Clin Oncol 19:558-67 [PubMed]
      4. Monoclonal antibodies
        1. Denosumab (inhibits Osteoclasts)

VIII. Prognosis

  1. Hypercalcemia of Malignancy is a poor cancer prognostic sign
  2. Associated with >50% mortality in 30 days

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Related Studies

Ontology: Humoral hypercalcemia of malignancy (disorder) (C0149911)

Definition (NCI) Hypercalcemia generally develops as a late complication of malignancy; its appearance has grave prognostic significance. It remains unclear, however, whether death is associated with hypercalcemic crisis (uncontrolled or recurrent progressive hypercalcemia) or with advanced disease. Symptoms include central nervous system impairment such as as delirium with prominent symptoms of personality change, cognitive dysfunction, disorientation, incoherent speech, and psychotic symptoms such as hallucinations and delusions, smooth muscle hypotonicity, and altered cardiovascular function.
Concepts Disease or Syndrome (T047)
MSH C562390
SnomedCT 47709007
Italian Ipercalcemia neoplastica
French Hypercalcémie liée à une tumeur maligne, Hypercalcémie d'origine maligne
German Hyperkalzaemie einer Malignitaet, Hyperkalzaemie bei Malignitaet
Japanese 悪性腫瘍に伴う高カルシウム血症, アクセイシュヨウニトモナウコウカルシウムケツショウ, アクセイシュヨウニトモナウコウカルシウムケッショウ
English HUMORAL HYPERCALCEMIA OF MALIGNANCY, Humoral hypercalcemia of malignancy (disorder), hhm, malignant hypercalcemia, hypercalcaemia of malignancy, hypercalcemia of malignancy, Humoral Hypercalcemia Of Malignancy, HHM, Humoral hypercalcemia of malignancy, MAHC, Malignancy associated hypercalcemia, Hypercalcaemia of malignancy, Hypercalcemia of malignancy, Malignancy associated hypercalcaemia, Malignant hypercalcaemia, Malignant hypercalcemia, Humoural hypercalcaemia of malignancy, Hypercalcemia of Malignancy
Czech Hyperkalcemie při malignitě
Hungarian Malignus betegséghez társuló hypercalcaemia, Malignus-hypercalcaemia
Spanish hipercalcemia humoral asociada con malignidad, hipercalcemia humoral maligna (trastorno), hipercalcemia humoral maligna, malignidad asociada con hipercalcemia, Hipercalcemia por enfermedad maligna
Portuguese Hipercalcemia de neoplasia maligna
Dutch hypercalciëmie door maligniteit