Hypercalcemia Treatment
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
- 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
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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