eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders
Hypercalcemia: Treatment & Medication
Updated: Jul 27, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment depends on the severity of symptoms and the underlying cause.2
- Volume expansion and saline diuresis
- Volume depletion results from uncontrolled symptoms leading to decreased intake and enhanced renal sodium loss. This tends to exacerbate or perpetuate the hypercalcemia by increasing Na+ reabsorption in the thick ascending limb of the loop of Henle (TALH). Thus, appropriate volume repletion with isotonic sodium chloride solution is an effective short-term treatment for hypercalcemia.
- Once volume is restored, simultaneous administration of loop diuretics blocks Na+ and calcium reabsorption in the TALH.
- Replacing ongoing sodium, potassium, chloride, and magnesium losses is important if prolonged sodium chloride and loop diuretic therapy is contemplated.
- Mobilization
- Immobilization aggravates hypercalcemia.
- Whenever possible, weightbearing mobilization should be encouraged.
- Reduction of gastrointestinal calcium absorption
- Reduction of dietary calcium and vitamin D intake is effective for treating hypercalcemia due to increased intestinal calcium absorption (eg, in idiopathic infantile hypercalcemia, ie, Williams syndrome).
- In vitamin D toxicity or extrarenal synthesis of 1,25(OH) D3 (eg, in sarcoidosis), prednisone may help reduce plasma calcium levels by reducing intestinal calcium absorption.
- Oral phosphate also can be used to form insoluble calcium phosphate in the gut.
- Inhibition of bone resorption
- Bisphosphonates inhibit osteoclastic bone resorption and are effective in the treatment of hypercalcemia due to conditions causing increased bone resorption and malignancy-related hypercalcemia.
- Pamidronate and etidronate can be given intravenously, while risedronate and alendronate may be effective as oral therapy.
- Calcitonin can be given intramuscularly or subcutaneously, but it becomes less effective after several days of use.
- Mithramycin blocks osteoclastic function and can be given for severe malignancy-related hypercalcemia. It has significant hepatic, renal, and marrow toxicity.
- Dialysis: Peritoneal or hemodialysis against calcium-free or lower calcium concentration dialysate solution is highly effective in lowering plasma calcium levels.
Surgical Care
Surgical care is directed toward reversing the underlying cause of hypercalcemia or repairing the orthopedic damage.3,4
- Prolonged hypercalcemia due to hyperparathyroidism may warrant surgical neck exploration and removal of 1 or more parathyroid glands. This is particularly appropriate if evidence of nephrolithiasis, osteoporosis, reduction of renal function, neuromuscular symptoms, or radiographic bone disease is present.
- Hypercalcemia due to malignancy, especially if due to a tumor that is producing PTHrP, may require surgical resection of the tumor.
- Orthopedic complications of prolonged hypercalcemia (eg, osteoporosis), complications of Paget disease, or complications of bony metastases may require orthopedic or neurosurgical intervention.
Consultations
Consultation with a surgeon or orthopedist may be required, as indicated.
Medication
The first therapy for symptomatic hypercalcemia is volume repletion. More severe cases require saline infusion with concomitant loop diuretics (eg, furosemide) to increase calcium excretion and lower levels rapidly. Other therapies, outlined below, are for longer-term management. Note, however, that no current therapies generally are effective for long-term outpatient therapy. Definitive treatment often requires surgical management.2
Clodronate (not available in the United States) can be given either IV or PO and may represent a better alternative in the future at a dose 1600-2400 mg/d. Ibandronate (not available in the United States) is approximately 50 times more potent than pamidronate and may be given as a single bolus rather than an infusion. Zoledronic acid is 100-850 times more potent than pamidronate and may be given as a bolus rather than an infusion.
Bisphosphonates
Inhibit bone reabsorption.
Pamidronate (Aredia)
Used after initial hydration to inhibit bone reabsorption and maintain low serum calcium levels, especially in hypercalcemia of malignancy and Paget disease.
Adult
Severe hypercalcemia: 90 mg IV over 24 h
Moderate hypercalcemia: 60 mg IV over 4 h or 90 mg IV over 24 h
Pediatric
Not established
None reported
Documented hypersensitivity; hypocalcemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate, magnesium, and potassium) once treatment begins; adequate intake of calcium and vitamin D are necessary to prevent severe hypocalcemia; caution when administering bisphosphonates in patients with active upper GI problems; do not coadminister with alendronate for osteoporosis in postmenopausal women
Etidronate (Didronel)
Reduces bone formation and does not alter renal tubular reabsorption of calcium. Does not affect hypercalcemia in patients with hyperparathyroidism.
Adult
7.5 mg/kg/d IV for 3 consecutive d
Pediatric
Not established
Coadministration with calcium-containing products and other multivalent cations decrease absorption
Documented hypersensitivity; hypocalcemia, renal impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate, magnesium, and potassium); maintain adequate intake of calcium and vitamin D to prevent severe hypocalcemia; caution if active upper GI problems; do not administer with alendronate for osteoporosis in postmenopausal women
Alendronate (Fosamax)
Available in the United States, but not yet indicated for treatment of hypercalcemia; alendronate probably is useful for long-term prevention of recurrence of hypercalcemia following use of more conventional therapy (ie, hydration and pamidronate). Useful in preventing and treating osteoporosis, which is a complication of prolonged mild hypercalcemia.
Adult
Not established; usual starting dose is 40 mg PO qam
Pediatric
Not established
None reported
Documented hypersensitivity; hypocalcemia; abnormalities of the esophagus; inability to stand upright for 30 min
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Must be taken at least 30 min before first food, beverage, or medication of the day and should be taken with large amounts of water; caution in renal impairment
Antineoplastic drugs
Some agents in this drug class can reduce bone turnover.
Gallium nitrate (Ganite)
Available in the United States. Use should be limited to those with extensive experience in this field (ie, oncologists).
Adult
200 mg/m2 IV infused over 24 h and repeated qd for 5 d
Pediatric
Not established
Nephrotoxic effects increase when administered with amphotericin B or aminoglycosides
Documented hypersensitivity; renal failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal failure
Plicamycin (Mithracin)
No longer manufactured and distributed in the United States. Inhibits bone resorption. Used only in cases of hypercalcemia due to malignancy; treatment can be repeated if necessary.
Adult
25 mcg/kg IV over 4-6 h
Pediatric
Not established
Coadministration with glucagon, calcitonin, and etidronate may increase toxicity
Documented hypersensitivity; thrombocytopenia, coagulation disorders, impairment of bone marrow function
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor platelets, prothrombin, and bleeding times periodically during therapy and for several days after last dose; discontinue therapy if significant prolongation of bleeding times occurs and thrombocytopenia is observed; correct any electrolyte imbalance (especially hypokalemia, hypocalcemia, and hypophosphatemia) prior to treatment
Antidote, hypercalcemia agents
Inhibit bone resorption and increase renal calcium excretion.
Calcitonin (Miacalcin, Osteocalcin)
Lowers elevated serum calcium in patients with multiple myeloma, carcinoma, or primary hyperparathyroidism. Expect higher response when serum calcium levels are high.
Onset of action is approximately 2 h following injection, and activity lasts for 6-8 h. May lower calcium levels for 5-8 d by approximately 9% if given q12h. IM route is preferred at multiple injection sites with dose > 2 mL.
Adult
4-8 IU/kg IM/SC q6-12h
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypocalcemia may occur; examine urine sediment during prolonged therapy
Glucocorticoids
Inhibit cytokine release and have a direct cytolytic effect on some tumor cells.
Prednisone (Deltasone, Orasone, Sterapred)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Adult
20-50 mg PO bid
Pediatric
Not established
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Minerals
Phosphate inhibits calcium absorption and promotes calcium deposition. Theorized to help bind dietary calcium, thus rendering it an unabsorbable calcium-phosphorous product, but used rarely.
Potassium phosphate (Neutra-Phos-K)
Increases urinary pyrophosphate and complexes with calcium, thus decreasing urinary calcium level, while pyridoxine results in a reduction of urinary oxalate excretion. All dosage forms must be mixed in 6-8 oz of water. Never give IV. Never give if renal function is abnormal or if serum phosphorous levels are > 3 mg/dL.
Adult
250-500 mg phosphorus/8-16 mmol PO tid
Pediatric
Not established
Magnesium-containing and aluminum-containing antacids or sucralfate can act as phosphate binders and decrease serum phosphate levels; potassium-sparing diuretics, ACE inhibitors, and salt substitutes may increase serum phosphate levels
Abnormal renal function, renal failure, serum phosphorous >4.5 mg/dL; IV administration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with renal insufficiency and metabolic alkalosis; admixture of phosphate and calcium in IV fluids can result in calcium phosphate precipitation
Calcimimetic Agent
Binds to and modulates the parathyroid calcium-sensing receptor, increases sensitivity to extracellular calcium, and reduces parathyroid hormone secretion.1,5
Marcocci et al performed an open-label, single-arm study to determine how effectively cinacalcet, a calcimimetic, reduces hypercalcemia in patients with intractable persistent primary hyperparathyroidism.6 The investigation, performed on 17 patients, included a 2- to 16-week titration phase and a maintenance phase of up to 136 weeks. By the end of the titration phase, serum calcium had been reduced in 15 patients by at least 1 mg/dL. Although 15 patients suffered adverse events related to treatment (most commonly, nausea, vomiting, and paresthesias), none of these were considered to be serious.
Cinacalcet (Sensipar)
Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium-sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and in hypercalcemia with parathyroid carcinoma.
Adult
Secondary hyperparathyroidism: 30 mg PO qd initially; titrate upward slowly (no more frequent than q2-4wk intervals) by 30-mg increments to target iPTH of 150-300 pg/mL
Take with meals or immediately following; do not crush, chew, or cut tablets
Hypercalcemia with parathyroid carcinoma: 30 mg PO qd initially; titrate q2-4wk as needed to normalize calcium levels by sequential doses of 30 mg bid, 60 mg bid, 90 mg bid, and 90 mg tid/qid
Take with meals or immediately following; do not crush, chew, or cut tablets
Pediatric
Not established
Strong CYP450 2D6 inhibitor; may increase serum levels of CYP 2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP450 3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease clearance
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2 mo (parathyroid carcinoma); do not initiate treatment if serum calcium level below 8.4 mg/dL; adynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting
More on Hypercalcemia |
| Overview: Hypercalcemia |
| Differential Diagnoses & Workup: Hypercalcemia |
 Treatment & Medication: Hypercalcemia |
| Follow-up: Hypercalcemia |
| Multimedia: Hypercalcemia |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
McKay CP, Portale A. Emerging topics in pediatric bone and mineral disorders 2008. Semin Nephrol. Jul 2009;29(4):370-8. [Medline].
Makras P, Papapoulos SE. Medical treatment of hypercalcaemia. Hormones (Athens). Apr-Jun 2009;8(2):83-95. [Medline]. [Full Text].
Bergenfelz AO, Jansson SK, Wallin GK, et al. Impact of modern techniques on short-term outcome after surgery for primary hyperparathyroidism: a multicenter study comprising 2,708 patients. Langenbecks Arch Surg. Jul 18 2009;[Medline].
Low TH, Clark J, Gao K, et al. Outcome of parathyroidectomy for patients with renal disease and hyperparathyroidism: predictors for recurrent hyperparathyroidism. ANZ J Surg. May 2009;79(5):378-82. [Medline].
Padhi D, Harris R. Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. [Medline].
Marcocci C, Chanson P, Shoback D, et al. Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. J Clin Endocrinol Metab. Jun 2 2009;[Medline].
al Zahrani A, Levine MA. Primary hyperparathyroidism. Lancet. Apr 26 1997;349(9060):1233-8. [Medline].
Allerheiligen DA, Schoeber J, Houston RE. Hyperparathyroidism. Am Fam Physician. Apr 15 1998;57(8):1795-802, 1807-8. [Medline].
Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. May 1 2003;67(9):1959-66. [Medline].
Falk S, Fallon M. ABC of palliative care. Emergencies. BMJ. Dec 6 1997;315(7121):1525-8. [Medline].
Ganong CA, Kappy MS. Hypercalcemia. In: Berman S, ed. Pediatric Decision Making. 3rd ed. St. Louis, Mo: Mosby-Year Book; 1996:. 128-31.
Hay WW Jr, Hayward AR, Levin MJ, Sondheimer JM, eds. Current Pediatric Diagnosis and Treatment. 14th ed. Stamford, Conn: Appleton & Lange; 1999:. 830-1.
Hoenderop JG, Nilius B, Bindels RJ. Molecular mechanism of active Ca2+ reabsorption in the distal nephron. Annu Rev Physiol. 2002;64:529-49. [Medline].
Inzucchi SE. Management of hypercalcemia. Diagnostic workup, therapeutic options for hyperparathyroidism and other common causes. Postgrad Med. May 2004;115(5):27-36. [Medline].
Lteif AN, Zimmerman D. Bisphosphonates for treatment of childhood hypercalcemia. Pediatrics. Oct 1998;102(4 Pt 1):990-3. [Medline].
Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. Aug 1997;103(2):134-45. [Medline].
Pearce SH. Calcium homeostasis and disorders of the calcium-sensing receptor. J R Coll Physicians Lond. Jan-Feb 1998;32(1):10-4. [Medline].
Postlethwaite RJ. Clinical Pediatric Nephrology. 2nd ed. New York, NY: Butterworth Heinemann; 1994.
Renton P. Radiology of rickets, osteomalacia and hyperparathyroidism. Hosp Med. May 1998;59(5):399-403. [Medline].
Rogers MJ, Watts DJ, Russell RG. Overview of bisphosphonates. Cancer. Oct 15 1997;80(8 Suppl):1652-60. [Medline].
Sharma OP. Vitamin D, calcium, and sarcoidosis. Chest. 1996;109(2):535-539. [Medline].
Strewler GJ. The physiology of parathyroid hormone-related protein. N Engl J Med. Jan 20 2000;342(3):177-85. [Medline].
Further Reading
Related eMedicine topics:
Hypercalcemia [Emergency Medicine]
Hypercalcemia [Pediatrics: General Medicine]
Hypercalcemia and Spinal Cord Injury
Hyperparathyroidism [Emergency Medicine]
Hyperparathyroidism [Endocrinology]
Hyperparathyroidism [Otolaryngology and Facial Plastic Surgery]
Hyperparathyroidism [Pediatrics: General Medicine]
Hyperparathyroidism, Primary
Hyperparathyroidism, Secondary
Hypocalcemia [Emergency Medicine]
Hypocalcemia [Nephrology]
Hypocalcemia [Pediatrics: General Medicine]
Milk-Alkali Syndrome
Nephrocalcinosis [Nephrology]
Nephrocalcinosis [Radiology]
Parathyroid Adenoma
Parathyroid Carcinoma
Parathyroid Physiology
Williams Syndrome
Clinical guidelines:
Cinacalcet for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis therapy. National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2007 Jan. 28 pages. NGC:005508
The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism. American Association of Clinical Endocrinologists - Medical Specialty Society
American Association of Endocrine Surgeons - Medical Specialty Society. 2005 Jan-Feb. 6 pages. NGC:004187
Clinical trials:
Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients
One Week Parathyroid Hormone-Related Protein (PTHrP) IV Dose Escalation Study
Keywords
hypercalcemia, parathyroid, hyperparathyroidism, serum calcium, Sensipar, high calcium levels, surgery parathyroid, parathyroidectomy, high serum calcium, calcium metabolism, excess calcium, calmodulin
