Endocrine Disease

Granulomatous Disease


  • Breast Cancer (see Breast Cancer)
  • Multiple Myeloma (see Multiple Myeloma)
  • Non-Hodgkin’s Lymphoma (see Lymphoma)
  • Prostate Cancer (see Prostate Cancer)
  • Renal Cell Carcinoma (see Renal Cancer)
    • Epidemiology
      • Hypercalcemia Occurs in 15% of Renal Cell Carcinoma Cases
    • Mechanisms
      • Osteolytic Bone Metastases
      • Parathyroid Hormone-Related Protein (PTHrp) Production
      • Increased Interleukin-6 (IL-6): which enhances the effect of PTHrp
      • Prostaglandin-Induced Enhancement of Bone Resorption
  • Squamous Cell Lung Cancer (see Lung Cancer)
    • Epidemiology
      • Squamous Cell Histology: accounts for 51% of paraneoplastic hypercalcemia cases in lung cancer
      • Adenocarcinoma Histology: accounts for 22% of paraneoplastic hypercalcemia cases in lung cancer
      • Small Cell Histology: accounts for 15% of paraneoplastic hypercalcemia cases in lung cancer
    • Mechanisms
      • Osteolytic Bone Metastases
      • Tumor Production of PTH-Related Protein (PTHrP), Calcitriol, or Osteoclast-Activating Factors
  • Other Squamous Cell Cancers


  • Immobilization
    • Epidemiology
      • Immobilization is a Common Etiology of Mild Hypercalcemia in Patients with Critical Illness
  • Rhabdomyolysis (see Rhabdomyolysis)
    • Approximately 30% of Patients with Rhabdomyolysis are Hypercalcemic During the Recovery/Diuretic Phase of Acute Kidney Injury Due to Acute Tubular Necrosis
      • Due to Increased 1,25(OH)2D Occurring During this Phase


Effects of Hypercalcemia on Cardiac Physiology

  • Hypercalcemia Shortens the Duration of Plateau of the Cardiac Fiber Action Potential


Diagnosis Based on Parathyroid Hormone (PTH) Level

Normal-High Parathyroid Hormone (PTH) Level

  • Parathyroid-Related Etiology
    • Normal-High 24 hr Urinary Calcium: suggests primary hyperparathyroidism
    • Low 24 hr Urinary Calcium: suggests benign familial hypercalcemia

Low Parathyroid Hormone (PTH) Level

  • Drug-Induced Hypercalcemia
  • Endocrine Disease
    • Adrenal Insufficiency
    • Hyperthyroidism
  • Granulomatous Disease
    • Sarcoidosis
    • Tuberculosis
  • Malignancy

Clinical Manifestations

General Comments

  • Relationship of Symptoms to Calcium Level
    • Clinical Symptoms in Hypercalcemia are Related to the Calcium Level and the Rapidity of Increase in the Calcium Level

Cardiovascular Manifestations

Gastrointestinal Manifestations

Neurologic Manifestations

Renal Manifestations


Normal Saline (see Normal Saline)

  • Mechanism
    • Normal Saline Increases the Glomerular Filtration Rate and Decreases Distal Tubular Sodium and Calcium Absorption
      • Normal Saline Typically Lowers the Serum Calcium 1.5-2.5 mg/dL
  • Dose: 3-4 L of normal saline per 24-48 hrs
  • Onset of Action: hours
  • Duration of Action: hours

Furosemide (Lasix) (see Furosemide)

  • Mechanism
    • Furosemide Inhibits Sodium and Calcium Absorption in Thick Ascending Loop of Henle
  • Dose: give only after intravenous fluid repletion
  • Onset of Action: hours
  • Duration of Action: hours

Calcitonin (see Calcitonin)

  • Mechanism
    • Calcitonin Decreases Bone Calcium Release/increases Renal Excretion (Useful for Diseases Characterized by Increased Bone Turnover)
      • Calcitonin Typically Lowers the Serum Calcium About 1-2 mg/dL
  • Dose: 4-8 μg/kg IM/SQ q6-8 hours
  • Onset of Action: hours
  • Duration of Action: transient (may be <24 hrs)

Pamidronate (see Pamidronate)

  • Mechanism
    • Bisphosphonates Bind to Hydroxyapatite
  • Dose: 60 mg IV over 4 hours
  • Onset of Action: 1-2 days (peak in 7 days)
  • Duration of Action : days-4 weeks
  • Adverse Effects

Prednisone (see Corticosteroids)

  • Indications Useful for Tumors/conditions Which Have 1,25-Vitamin D3 as Part of Their Mechanism)
  • Mechanism
    • Prednisone Increases Calcium Excretion
  • Dose
    • Prednisone: 40-100 mg/day in 4 divided doses x 3-5 days
    • Hydrocortisone: 100 q8hrs X 3-5 days
  • Onset of Action: hours
  • Duration of Action: days

Gallium Nitrate (see Gallium Nitrate)

  • Mechanism
    • Gallium Nitrate Typically Lowers the Serum Calcium 1-5 mg/dL
  • Dose: 200 mg/m2 per day IV for 5 days (continuous)
  • Onset of Action: peaks at 8 days
  • Duration of Action: days-weeks
  • Adverse Effects: renal

Mithramycin (Plicamycin) (see Mithramycin)

  • Mechanism
    • Mithramycin Inhibits Osteoclasts
      • Mithramycin Lowers the Serum Calcium 1-5 mg/dl
  • Dose: 15-25 ug/kg IV over 4-6 hours q24-48 hours
  • Onset of Action: 12 hours
  • Duration of Action: days-weeks
  • Adverse Effects

Hemodialysis with Low Calcium Dialysate (see Hemodialysis)

  • Indications
    • Emergent Severe Hypercalcemia

Indomethacin/Aspirin (see Indomethacin and Acetylsalicylic Acid)

  • Indications
    • Malignancy-Associated Hypercalcemia
    • Humoral Hypercalcemia
    • Hypercalcemia with Osteolytic Lesions
  • Mechanism
    • Indomethacin/Aspirin Inhibit Prostaglandin E Synthesis

Denosumab (Xgeva, Prolia) (see Denosumab)

  • Indications
    • Hypercalcemia of Malignancy: Xgeva is FDA-approved for this indication