hypercalcemia
HYPERCALCEMIA
Hypercalcemia is having serum calcium level of >10.5 mg/dL (>2.5 mmol/L).
Mild hypercalcemia is usually asymptomatic. While, more severe hypercalcemia has a constellation of clinical manifestations commonly described as "bones, abdominal moans, stones & groans."
Etiologies may be parathyroid-dependent or parathyroid independent.
Surgery is the treatment of choice for hypercalcemic patients with classic symptoms or complications of primary hyperparathyroidism.

Principles of Therapy

  • Surgery is the treatment of choice for patients w/ classic symptoms or complications of primary hyperparathyroidism

Pharmacotherapy

  • There is no convincing data to support the effectiveness of medical therapy in long-term management of primary hyperparathyroidism

Primary Hyperparathyroidism

Estrogen Replacement

  • In postmenopausal women, estrogen replacement may lower serum Ca w/ no effect on parathyroid hormone
  • Protects against bone loss

Bisphosphonates

  • Further study is needed to prove usefulness in mild hypercalcemia caused by primary hyperparathyroidism

Acute Severe Hypercalcemia

Loop Diuretics

  • Administer as aggressively as patient’s cardiac status will allow
  • Effects: Stimulates natriuresis which is accompanied by calciuresis
    • Direct calciuretic effects may be achieved w/ high doses (Furosemide 100 mg/hr)
    • Serum Ca may decrease by ≥1 mmol/L (4 mg/dL) within 24 hours
    • Urine Ca excretion may exceed >25 mmol/dL

Bisphosphonates

  • Actions: High affinity for bone especially in areas of increased bone turnover where they inhibit bone resorption
  • Useful for hypercalcemia due to enhanced osteoclastic bone resorption
  • Effects: Depending on agent used may take a few days to reach normocalcemia
    • Normocalcemia is prolonged (depending on agent, may be for a month or longer)
  • Though related structurally, bisphosphonates differ in potency, efficacy, route of administration, toxicity & side effects

Calcitonin

  • Actions: Blocks bone resorption through receptors on osteoclasts, increases urinary Ca excretion by blocking renal tubular Ca reabsorption
  • Effects: Can be seen within a few hours of administration
    • Minimal lowering of serum Ca
  • May use in combination w/ rehydration & saline diuresis within the 1st 24 hours of treatment until bisphosphonates take effect

Corticosteroid Hormones

  • Actions: In pharmacologic doses cause an increase in urinary Ca excretion & decrease in intestinal Ca absorption
    • Cause negative skeletal Ca balance
    • May also have a direct cytolytic effect on some tumor cells
  • Effects: Hypocalcemic effect develops over several days
  • Benefit is seen in hypercalcemia caused by certain osteolytic malignancies, multiple myeloma, leukemia, breast cancer & Hodgkin’s disease
  • Effective in treating hypercalcemia caused by vitamin D intoxication & sarcoidosis

Vitamin D Intoxication

  • Discontinue vitamin D
  • Restrict dietary Ca intake
  • Ensure adequate hydration

Granulomatous Diseases

  • Avoid excessive sunlight exposure
  • Limit Ca & vitamin intake

Other Drug for Hypercalcemia

Cinacalcet

  • A calcimimetic agent indicated for hypercalcemic patients w/ parathyroid carcinoma
  • It directly lowers parathyroid levels by increasing the sensitivity of the Ca-sensing receptor on the parathyroid gland; results in concomitant decrease in serum Ca
  • Clinical trials have shown prolonged normalization of serum Ca levels
Denosumab
  • A monoclonal antibody directed against receptor activator of nuclear factor kappa-beta ligand (RANKL)
  • Studies have shown that it is effective for the management of hypercalcemia of malignancy refractory to bisphosphonate therapy
  • It is also an option in patients in whom IV bisphosphonate therapy is contraindicated due to severe renal impairment

Measures to Lower Serum Calcium

Mild Asymptomatic Hypercalcemia
  • Patients w/ primary hyperparathyroidism often have mild & prolonged hypercalcemia, which results in mild or no symptoms
  • Start measures to decrease serum Ca
    • Stop any medications that may cause hypercalcemia eg thiazide diuretics
    • Patient should avoid all diuretics
  • Counsel patient to:
    • Avoid prolonged immobilization
    • Maintain adequate hydration
    • Patient should seek immediate medical attention for illness that may cause dehydration especially severe vomiting or diarrhea
  • If patient becomes symptomatic, they should be referred to a surgeon immediately
Acute Severe Hypercalcemia
  • Monitor patient closely preferably in ICU setting especially if using forced diuresis
    • Monitor central venous pressure, plasma or urine electrolytes, may need to catheterize the bladder
  • Diagnostic testing should occur while aggressive Ca-lowering treatment is initiated
  • Primary hyperparathyroidism will benefit from immediate surgery
Fluids
  • Restore normal hydration
    • Patient is usually dehydrated from vomiting, inanition or defective urinary concentrating ability
  • If serum Ca >2.8 mmol/L (11.2 mg/dL), patient needs to be instructed to drink 2-3 L/day of low Ca liquids
  • If serum Ca >3 mmol/L (12 mg/dL)
    • Infuse NaCl 0.9% at 2-6 L/day IV which will increase calciuria
    • Loop diuretic may be added to improve diuresis
  • K & Mg depletion needs to be prevented
If diuresis proves unsuccessful:
  • Hemodialysis is the treatment of choice
  • Dialysis bath should be free of or low in Ca
  • Effects of dialysis: Ca-free peritoneal dialysis can remove 5-12.5 mmol (200-500 mg) of Ca in 24-48 hours
    • Serum Ca may be lowered by 0.7-3 mmol/L (3-12 mg/dL)
  • Phosphate concentration needs to be monitored
    • Add phosphate supplements to diet if necessary
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