Hypercalcemia Treatment

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

• 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

• 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

• 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

• 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

• 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

• 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