II. Epidemiology

  1. Incidence: 10-30% of cancer patients

III. Mechanisms

  1. Paraneoplastic syndromes (nearly all cases)
    1. Tumor secretes Parathyroid Hormone related peptide or PTHrP (80% of all cases)
      1. Present in Squamous Cell Carcinoma and Lymphoma
      2. Results in increased Calcium reabsorption in Kidney
    2. Osteoclast-Activating factor production (20% of all cases)
      1. Present in Multiple Myeloma and metastases
      2. Results in osteolysis
    3. Endogenous Calcitriol (Vitamin D, 1,25-dihydroxyvitamin D, <1% of all cases)
      1. Present in Lymphomas
      2. Calcitriol acts as a bone-resorbing Cytokine
  2. Other rare mechanisms
    1. Immobilization
    2. Medications
    3. Parathyroid carcinoma

IV. Causes: Primarily Breast, lung and Bone Cancers

V. Symptoms

  1. See Hypercalcemia
  2. Altered Level of Consciousness, confusion to coma
  3. Gastrointestinal Symptoms
    1. Nausea or Vomiting
    2. Constipation
    3. Anorexia
  4. Dehydration
    1. Acute Kidney Injury
    2. Generalized weakness
    3. Excessive Thirst and polydipsia
    4. Decreased Urine Output

VI. Labs

  1. Serum Electrolytes
  2. Serum Calcium
    1. Adjust for albumin, as Malnutrition is common (obtain Ionized Calcium if available)
    2. Mild Hypercalcemia: 10.5 to 11.9 mg/dl
    3. Moderate Hypercalcemia: 12.0 to 13.9 mg/dl
    4. Severe Hypercalcemia: >14 mg/dl

VIII. Management

  1. See Hypercalcemia for other management
  2. Consult Oncology, Endocrinology, Nephrology
  3. Acute Management
    1. Intravenous Fluids as Initial Management ( emergency department)
      1. Aggressive rehydration alone normalizes Serum Calcium in 30% of cases even within 12 hours
      2. Start 200 to 500 ml/hour with goal Urine Output 100-150 ml/hour
      3. Requires up to 4 liters Lactated Ringers or Normal Saline per 24 hours
  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. Indicated calcitriol overproduction as mechanism for Hypercalcemia
        2. Decrease intestinal Calcium absorption
      2. Calcitonin
        1. Calcitonin 4 IU/kg IM or SQ
        2. Inhibits Osteoclasts (but diminishing returns after first dose due to tachyphylaxis)
      3. Bisphosphonates
        1. Inhibit Osteoclast mediated bone resorption (delayed effect over 1-3 days)
        2. Zoledronic acid: 4 mg IV over 15 min (preferred over Pamidronate)
        3. Pamidronate (Aredia) 60-90 mg IV given over 2 hours q4 hours
        4. Major (2001) J Clin Oncol 19:558-67 [PubMed]
      4. Monoclonal antibodies
        1. Denosumab (inhibits Osteoclasts)
  7. Other measures
    1. Hemodialysis Indications
      1. Refractory Acute Kidney Injury (GFR <20)
      2. Total Serum Calcium >18 mg/dl
      3. Congestive Heart Failure
      4. Neurologic Deficits
    2. Loop Diuretics (e.g. Furosemide)
      1. Indicated in Renal Failure or Congestive Heart Failure
      2. Furosemide 10-20 mg IV q6-12 hours after initial rehydration

IX. Prognosis

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

X. References

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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